NO116055B - - Google Patents
Info
- Publication number
- NO116055B NO116055B NO16395066A NO16395066A NO116055B NO 116055 B NO116055 B NO 116055B NO 16395066 A NO16395066 A NO 16395066A NO 16395066 A NO16395066 A NO 16395066A NO 116055 B NO116055 B NO 116055B
- Authority
- NO
- Norway
- Prior art keywords
- ether
- chloroform
- total
- tropine
- methoxy
- Prior art date
Links
- 239000002253 acid Substances 0.000 claims description 28
- 238000004519 manufacturing process Methods 0.000 claims description 4
- 229940079593 drug Drugs 0.000 claims description 3
- 239000003814 drug Substances 0.000 claims description 3
- 238000000034 method Methods 0.000 claims description 3
- 150000007513 acids Chemical class 0.000 claims description 2
- 125000000468 ketone group Chemical group 0.000 claims description 2
- 125000003198 secondary alcohol group Chemical group 0.000 claims description 2
- 229960000396 atropine Drugs 0.000 claims 1
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 229
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 215
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 137
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 120
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 68
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 67
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 52
- -1 lithium aluminum hydride Chemical compound 0.000 description 52
- 229910052938 sodium sulfate Inorganic materials 0.000 description 46
- 235000011152 sodium sulphate Nutrition 0.000 description 46
- 239000011541 reaction mixture Substances 0.000 description 45
- 239000000203 mixture Substances 0.000 description 43
- 239000002026 chloroform extract Substances 0.000 description 41
- 238000001816 cooling Methods 0.000 description 37
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 34
- 239000000243 solution Substances 0.000 description 34
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 29
- 150000002148 esters Chemical class 0.000 description 23
- MTZQAGJQAFMTAQ-UHFFFAOYSA-N ethyl benzoate Chemical compound CCOC(=O)C1=CC=CC=C1 MTZQAGJQAFMTAQ-UHFFFAOYSA-N 0.000 description 18
- 239000013078 crystal Substances 0.000 description 16
- 239000005711 Benzoic acid Substances 0.000 description 15
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 14
- 229910052708 sodium Inorganic materials 0.000 description 14
- 239000011734 sodium Substances 0.000 description 14
- 238000006243 chemical reaction Methods 0.000 description 13
- 229940057613 veratrum Drugs 0.000 description 12
- 238000001953 recrystallisation Methods 0.000 description 11
- 239000002904 solvent Substances 0.000 description 11
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 10
- WPYMKLBDIGXBTP-UHFFFAOYSA-N Benzoic acid Natural products OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 10
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 9
- 239000000908 ammonium hydroxide Substances 0.000 description 9
- 239000007868 Raney catalyst Substances 0.000 description 8
- NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 8
- 229910000564 Raney nickel Inorganic materials 0.000 description 8
- 239000007864 aqueous solution Substances 0.000 description 8
- DULCUDSUACXJJC-UHFFFAOYSA-N benzeneacetic acid ethyl ester Natural products CCOC(=O)CC1=CC=CC=C1 DULCUDSUACXJJC-UHFFFAOYSA-N 0.000 description 8
- 239000003054 catalyst Substances 0.000 description 8
- KJFMBFZCATUALV-UHFFFAOYSA-N phenolphthalein Chemical compound C1=CC(O)=CC=C1C1(C=2C=CC(O)=CC=2)C2=CC=CC=C2C(=O)O1 KJFMBFZCATUALV-UHFFFAOYSA-N 0.000 description 8
- 235000010233 benzoic acid Nutrition 0.000 description 7
- 238000001704 evaporation Methods 0.000 description 7
- 230000008020 evaporation Effects 0.000 description 7
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 6
- 238000002156 mixing Methods 0.000 description 6
- 238000010992 reflux Methods 0.000 description 6
- CYHOMWAPJJPNMW-JIGDXULJSA-N tropine Chemical class C1[C@@H](O)C[C@H]2CC[C@@H]1N2C CYHOMWAPJJPNMW-JIGDXULJSA-N 0.000 description 6
- 241000489523 Veratrum Species 0.000 description 5
- 238000009835 boiling Methods 0.000 description 5
- 239000000155 melt Substances 0.000 description 5
- TWNQGVIAIRXVLR-UHFFFAOYSA-N oxo(oxoalumanyloxy)alumane Chemical compound O=[Al]O[Al]=O TWNQGVIAIRXVLR-UHFFFAOYSA-N 0.000 description 5
- XQJMXPAEFMWDOZ-UHFFFAOYSA-N 3exo-benzoyloxy-tropane Natural products CN1C(C2)CCC1CC2OC(=O)C1=CC=CC=C1 XQJMXPAEFMWDOZ-UHFFFAOYSA-N 0.000 description 4
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 4
- QQXLDOJGLXJCSE-UHFFFAOYSA-N N-methylnortropinone Natural products C1C(=O)CC2CCC1N2C QQXLDOJGLXJCSE-UHFFFAOYSA-N 0.000 description 4
- QIZDQFOVGFDBKW-DHBOJHSNSA-N Pseudotropine Natural products OC1C[C@@H]2[N+](C)[C@H](C1)CC2 QIZDQFOVGFDBKW-DHBOJHSNSA-N 0.000 description 4
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical class [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 4
- 239000003610 charcoal Substances 0.000 description 4
- 238000001035 drying Methods 0.000 description 4
- 239000000284 extract Substances 0.000 description 4
- RFHABUQANXJNQS-UHFFFAOYSA-N methyl 9h-xanthene-9-carboxylate Chemical compound C1=CC=C2C(C(=O)OC)C3=CC=CC=C3OC2=C1 RFHABUQANXJNQS-UHFFFAOYSA-N 0.000 description 4
- 239000003208 petroleum Substances 0.000 description 4
- 235000002639 sodium chloride Nutrition 0.000 description 4
- 238000003756 stirring Methods 0.000 description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 3
- 229910052799 carbon Inorganic materials 0.000 description 3
- DAOQKFHSVVIUKC-UHFFFAOYSA-N ethyl 9h-fluorene-9-carboxylate Chemical compound C1=CC=C2C(C(=O)OCC)C3=CC=CC=C3C2=C1 DAOQKFHSVVIUKC-UHFFFAOYSA-N 0.000 description 3
- 125000004494 ethyl ester group Chemical group 0.000 description 3
- 239000012458 free base Substances 0.000 description 3
- 229960002510 mandelic acid Drugs 0.000 description 3
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Substances [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 3
- 230000035484 reaction time Effects 0.000 description 3
- 229920006395 saturated elastomer Polymers 0.000 description 3
- 239000011780 sodium chloride Substances 0.000 description 3
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 2
- NFHKZAUDRWRXMZ-UHFFFAOYSA-N 2-chloro-2,2-diphenylacetyl chloride Chemical compound C=1C=CC=CC=1C(Cl)(C(=O)Cl)C1=CC=CC=C1 NFHKZAUDRWRXMZ-UHFFFAOYSA-N 0.000 description 2
- LAUFPZPAKULAGB-UHFFFAOYSA-N 4-butoxybenzoic acid Chemical compound CCCCOC1=CC=C(C(O)=O)C=C1 LAUFPZPAKULAGB-UHFFFAOYSA-N 0.000 description 2
- IWYDHOAUDWTVEP-UHFFFAOYSA-N R-2-phenyl-2-hydroxyacetic acid Natural products OC(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-N 0.000 description 2
- GPVDHNVGGIAOQT-UHFFFAOYSA-N Veratric acid Natural products COC1=CC=C(C(O)=O)C(OC)=C1 GPVDHNVGGIAOQT-UHFFFAOYSA-N 0.000 description 2
- 230000002378 acidificating effect Effects 0.000 description 2
- 230000010933 acylation Effects 0.000 description 2
- 238000005917 acylation reaction Methods 0.000 description 2
- 238000006136 alcoholysis reaction Methods 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 238000009903 catalytic hydrogenation reaction Methods 0.000 description 2
- OKSWMMZQZJBIKC-UHFFFAOYSA-N ethyl 2-cyclohexyl-2-hydroxy-2-phenylacetate Chemical compound C=1C=CC=CC=1C(O)(C(=O)OCC)C1CCCCC1 OKSWMMZQZJBIKC-UHFFFAOYSA-N 0.000 description 2
- KEFDYKRSOVELMH-UHFFFAOYSA-N ethyl 2-cyclohexyl-2-phenylacetate Chemical compound C=1C=CC=CC=1C(C(=O)OCC)C1CCCCC1 KEFDYKRSOVELMH-UHFFFAOYSA-N 0.000 description 2
- JGIQCXPHDHHHMN-UHFFFAOYSA-N ethyl 2-phenoxybenzoate Chemical compound CCOC(=O)C1=CC=CC=C1OC1=CC=CC=C1 JGIQCXPHDHHHMN-UHFFFAOYSA-N 0.000 description 2
- LMXMLKHKWPCFTG-UHFFFAOYSA-N ethyl 4-butoxybenzoate Chemical compound CCCCOC1=CC=C(C(=O)OCC)C=C1 LMXMLKHKWPCFTG-UHFFFAOYSA-N 0.000 description 2
- 239000006260 foam Substances 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 235000011121 sodium hydroxide Nutrition 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 150000008303 tropinone derivatives Chemical class 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- QBYIENPQHBMVBV-HFEGYEGKSA-N (2R)-2-hydroxy-2-phenylacetic acid Chemical compound O[C@@H](C(O)=O)c1ccccc1.O[C@@H](C(O)=O)c1ccccc1 QBYIENPQHBMVBV-HFEGYEGKSA-N 0.000 description 1
- CYHOMWAPJJPNMW-UHFFFAOYSA-N 8-methyl-8-azabicyclo[3.2.1]octan-3-ol Chemical class C1C(O)CC2CCC1N2C CYHOMWAPJJPNMW-UHFFFAOYSA-N 0.000 description 1
- 229930000680 A04AD01 - Scopolamine Natural products 0.000 description 1
- STECJAGHUSJQJN-GAUPFVANSA-N Hyoscine Natural products C1([C@H](CO)C(=O)OC2C[C@@H]3N([C@H](C2)[C@@H]2[C@H]3O2)C)=CC=CC=C1 STECJAGHUSJQJN-GAUPFVANSA-N 0.000 description 1
- STECJAGHUSJQJN-UHFFFAOYSA-N N-Methyl-scopolamin Natural products C1C(C2C3O2)N(C)C3CC1OC(=O)C(CO)C1=CC=CC=C1 STECJAGHUSJQJN-UHFFFAOYSA-N 0.000 description 1
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 1
- 239000003929 acidic solution Substances 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 230000005587 bubbling Effects 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 239000012230 colorless oil Substances 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- FLKPEMZONWLCSK-UHFFFAOYSA-N diethyl phthalate Chemical compound CCOC(=O)C1=CC=CC=C1C(=O)OCC FLKPEMZONWLCSK-UHFFFAOYSA-N 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- SAXHIDRUJXPDOD-UHFFFAOYSA-N ethyl hydroxy(phenyl)acetate Chemical compound CCOC(=O)C(O)C1=CC=CC=C1 SAXHIDRUJXPDOD-UHFFFAOYSA-N 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 238000005187 foaming Methods 0.000 description 1
- 229960000857 homatropine Drugs 0.000 description 1
- 230000036571 hydration Effects 0.000 description 1
- 238000006703 hydration reaction Methods 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- 239000012280 lithium aluminium hydride Substances 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 230000020477 pH reduction Effects 0.000 description 1
- 230000003285 pharmacodynamic effect Effects 0.000 description 1
- 229940075930 picrate Drugs 0.000 description 1
- OXNIZHLAWKMVMX-UHFFFAOYSA-M picrate anion Chemical compound [O-]C1=C([N+]([O-])=O)C=C([N+]([O-])=O)C=C1[N+]([O-])=O OXNIZHLAWKMVMX-UHFFFAOYSA-M 0.000 description 1
- 229940072033 potash Drugs 0.000 description 1
- 235000015320 potassium carbonate Nutrition 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 235000011181 potassium carbonates Nutrition 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- CYHOMWAPJJPNMW-RNLVFQAGSA-N pseudotropine Chemical class C1[C@H](O)C[C@H]2CC[C@@H]1N2C CYHOMWAPJJPNMW-RNLVFQAGSA-N 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 238000007127 saponification reaction Methods 0.000 description 1
- 238000009738 saturating Methods 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- STECJAGHUSJQJN-FWXGHANASA-N scopolamine Chemical compound C1([C@@H](CO)C(=O)O[C@H]2C[C@@H]3N([C@H](C2)[C@@H]2[C@H]3O2)C)=CC=CC=C1 STECJAGHUSJQJN-FWXGHANASA-N 0.000 description 1
- 229960002646 scopolamine Drugs 0.000 description 1
Classifications
-
- F—MECHANICAL ENGINEERING; LIGHTING; HEATING; WEAPONS; BLASTING
- F21—LIGHTING
- F21S—NON-PORTABLE LIGHTING DEVICES; SYSTEMS THEREOF; VEHICLE LIGHTING DEVICES SPECIALLY ADAPTED FOR VEHICLE EXTERIORS
- F21S11/00—Non-electric lighting devices or systems using daylight
-
- E—FIXED CONSTRUCTIONS
- E06—DOORS, WINDOWS, SHUTTERS, OR ROLLER BLINDS IN GENERAL; LADDERS
- E06B—FIXED OR MOVABLE CLOSURES FOR OPENINGS IN BUILDINGS, VEHICLES, FENCES OR LIKE ENCLOSURES IN GENERAL, e.g. DOORS, WINDOWS, BLINDS, GATES
- E06B7/00—Special arrangements or measures in connection with doors or windows
- E06B7/02—Special arrangements or measures in connection with doors or windows for providing ventilation, e.g. through double windows; Arrangement of ventilation roses
- E06B7/08—Louvre doors, windows or grilles
- E06B7/084—Louvre doors, windows or grilles with rotatable lamellae
-
- E—FIXED CONSTRUCTIONS
- E06—DOORS, WINDOWS, SHUTTERS, OR ROLLER BLINDS IN GENERAL; LADDERS
- E06B—FIXED OR MOVABLE CLOSURES FOR OPENINGS IN BUILDINGS, VEHICLES, FENCES OR LIKE ENCLOSURES IN GENERAL, e.g. DOORS, WINDOWS, BLINDS, GATES
- E06B9/00—Screening or protective devices for wall or similar openings, with or without operating or securing mechanisms; Closures of similar construction
- E06B9/24—Screens or other constructions affording protection against light, especially against sunshine; Similar screens for privacy or appearance; Slat blinds
- E06B9/26—Lamellar or like blinds, e.g. venetian blinds
- E06B9/264—Combinations of lamellar blinds with roller shutters, screen windows, windows, or double panes; Lamellar blinds with special devices
Landscapes
- Engineering & Computer Science (AREA)
- Structural Engineering (AREA)
- Civil Engineering (AREA)
- Architecture (AREA)
- Life Sciences & Earth Sciences (AREA)
- Sustainable Development (AREA)
- General Engineering & Computer Science (AREA)
- Wing Frames And Configurations (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Non-Portable Lighting Devices Or Systems Thereof (AREA)
Description
Fremgangsmåte for fremstilling av esterlignende 6-alkoksy-tropin-derivater. Process for the preparation of ester-like 6-Alkoxy-tropine derivatives.
Det har vist seg at det er mulig å komme frem til esterlignende derivater av tropin med formelen I It has been shown that it is possible to arrive at ester-like derivatives of tropine with the formula I
ved at man i tropinonderivater med formelen II in that in tropinone derivatives with the formula II
hvor Rx og R2 har samme betydning som ovenfor, reduserer ketogruppen til en sekundær alkoholgruppe og forestrer de tro-pan-3-ol-derivater som derved oppnås, på i og for seg kjent måte med syrer med formelen HOOC.R... where Rx and R2 have the same meaning as above, reduces the keto group to a secondary alcohol group and esterifies the tro-pan-3-ol derivatives thereby obtained, in a manner known per se, with acids of the formula HOOC.R...
Fremstillingen" av de nevnte tropinon-derivater er beskrevet i forskjellige paten-ter og dessuten i Heiv. Chim. Acta 37, 495 og 649 (1954). Reduksjonen kan utføres på kjent måte, f. eks. ved katalytisk hydrering med eller uten trykk, ved normal eller forhøyet temperatur, med natrium i en alkohol, eller ved behandling med litium-aluminium-hydrid. Katalytisk hydrering fører til tropinderivater, reduksjon med natrium og alkohol til pseudotropinderi-vater. The preparation" of the aforementioned tropinone derivatives is described in various patents and also in Heiv. Chim. Acta 37, 495 and 649 (1954). The reduction can be carried out in a known manner, e.g. by catalytic hydrogenation with or without pressure , at normal or elevated temperature, with sodium in an alcohol, or by treatment with lithium aluminum hydride Catalytic hydrogenation leads to tropine derivatives, reduction with sodium and alcohol to pseudotropine derivatives.
Acyleringen kan eksempelvis foregå ved alkoholyse, idet et tropinderivat oppvarmes med en ester med formelen alkyl-OOC.R3 i nærvær av natriummetall og derved overføres til den tilsvarende tropin-ester. Også omsetningen av et tropin med et syreklorid med formelen C10C.R3 fører til estrene i henhold til oppfinnelsen. The acylation can, for example, take place by alcoholysis, whereby a tropine derivative is heated with an ester of the formula alkyl-OOC.R3 in the presence of sodium metal and thereby transferred to the corresponding tropine ester. Also the reaction of a tropine with an acid chloride of the formula C10C.R3 leads to the esters according to the invention.
De esterlignende 6-alkoksy-tropin-derivater som oppnås i henhold til forelig-gende fremgangsmåte skal, på grunn av sin sterke farmakodynamiske virkning brukes som medikament med skopolamin-atrdpinvirkning, men tjener også som mel-lomprodukt for fremstilling av disse. Due to their strong pharmacodynamic effect, the ester-like 6-alkoxy-tropine derivatives obtained according to the present method are to be used as drugs with scopolamine anti-inflammatory action, but also serve as intermediates for their production.
Eksempel 1: 6-metoksy-tropin-xanten-9- karbon- syreester: 5 g 6-metoksy-tropinon-hydroklorid blir hydrert i 50 ems abs metanol i autoklav med Raney-nikkel i 5 timer ved 40 —45° og et begynnelsestrykk på 60 at. Man filtrerer av fra katalysatoren og fordamper den største del av oppløsningsmidlet i vakuum, hvorved 6-metoksy-tropin-hydro-kloridet, C9-H1802NC1 krystalliserer ut. Etter omkrystallisering fra metanol har det et smp. på 205—206°. Example 1: 6-methoxy-tropine-xanthene-9- carbon acid ester: 5 g of 6-methoxytropinone hydrochloride is hydrated in 50 ems abs methanol in an autoclave with Raney nickel for 5 hours at 40-45° and an initial pressure of 60 at. The catalyst is filtered off and the largest part of the solvent is evaporated in vacuo, whereby the 6-methoxytropine hydrochloride, C9-H1802NC1 crystallizes out. After recrystallization from methanol it has a m.p. at 205-206°.
Hydreringen kan like godt utføres med fri base. Man oppvarmer nå en blanding av 3 g 6-metoksy-tropin og 8,4 g xanten-9-karbonsyre-metylester med ca. 0,1 g natriummetall i 30 timer i vakuum (ca. 1 mm The hydration can just as well be carried out with a free base. A mixture of 3 g of 6-methoxytropine and 8.4 g of xanthene-9-carboxylic acid methyl ester is now heated with approx. 0.1 g of sodium metal for 30 hours in a vacuum (approx. 1 mm
Hg) til 130°, opptar reaksjonsblandingen Hg) to 130°, occupies the reaction mixture
etter avkjølingen i 60 cm» 2-n.saltsyre og after cooling in 60 cm» 2-n.hydrochloric acid and
ekstraherer med ialt 160 ems eter. Det vandige saltsure lag blir rystet ut med ialt 300 extract with a total of 160 ems ether. The aqueous hydrochloric acid layer is shaken out with a total of 300
cm3 kloroform, og kloroformekstrakten som er tørket over natriumsulfat blir inndampet i vakuum. Resten, 6-metoksy-tropin-xanten-9-karbonsyreester-hydroklorid, kunne ikke bringes til å krystallisere og ble direkte overført til den frie base. cm3 of chloroform, and the chloroform extract which has been dried over sodium sulfate is evaporated in vacuo. The residue, 6-methoxytropine-xanthene-9-carboxylic acid ester hydrochloride, could not be brought to crystallize and was directly transferred to the free base.
Eksempel 2: 6-metoksy-pseudo-tropin-bensil'syre ester-hydroklorid : Til en kokende oppløsning av 6,5 g 6-metoksy-tropinon i 65 ems abs etanol blir det porsjonsvis og under omrøring i løpet av 2 timer satt 6,5 g natrium. Reaksjonsblandingen destilleres med vanndamp, resten ekstraheres med ialt 200 ems eter, eteren avdampes etter tørking over natriumsulfat, og resten fraksjoneres i høy-vakuum. 6-metoksy-pseudo-tropin koker ved 102—107°, ved 0,6 mm Hg. Example 2: 6-Methoxy-pseudo-tropine-benzylic acid ester hydrochloride : To a boiling solution of 6.5 g of 6-methoxytropinone in 65 ems abs ethanol, 6.5 g of sodium are added portionwise and with stirring over the course of 2 hours. The reaction mixture is distilled with steam, the residue is extracted with a total of 200 ems of ether, the ether is evaporated after drying over sodium sulphate, and the residue is fractionated in high vacuum. 6-Methoxy-pseudo-tropine boils at 102—107°, at 0.6 mm Hg.
En blanding av 1,5 g 6-metoksy-pseudo-tropin og 4,47 g bensilsyre-etylester oppvarmes med ca. 0,1 g natriummetall i 30 timer i vakuum (ca. 1 mm Hg) til 110°, reaksjonsblandingen blir etter avkjøling opptatt i 30 ems 2-n.saltsyre og ekstraheres med ialt 150 cm» eter. Det vandige saltsure lag blir rystet ut med ialt 250 cm3 kloroform, og kloroformekstrakten, som er tørket over natriumsulfat, blir inndampet i vakuum. Resten oppløses i litt metanol, filtreres gjennom benkull, og hydrokloridet bringes til å krystallisere ved tilsetning av eter. 6-metoksy-pseudo-tropin-bensilsyreester-hydroklorid krystalliserer fra metanol/eter i krystaller med smp. 237—239° A mixture of 1.5 g of 6-methoxy-pseudo-tropine and 4.47 g of benzylic acid ethyl ester is heated with approx. 0.1 g of sodium metal for 30 hours in a vacuum (approx. 1 mm Hg) at 110°, the reaction mixture is, after cooling, taken up in 30 ems of 2-n hydrochloric acid and extracted with a total of 150 cm" of ether. The aqueous hydrochloric acid layer is shaken out with a total of 250 cm3 of chloroform, and the chloroform extract, which has been dried over sodium sulfate, is evaporated in vacuo. The residue is dissolved in a little methanol, filtered through bone charcoal, and the hydrochloride is caused to crystallize by adding ether. 6-Methoxy-pseudo-tropine-benzyl ester hydrochloride crystallizes from methanol/ether in crystals of m.p. 237—239°
(sp.). (sp.).
6-metoksy-pseudo-tropin-bensilsyreester smelter etter omkrystallisering fra acetonpetroleter ved 121—123°. 6-Methoxy-pseudo-tropine-benzylic acid ester melts after recrystallization from acetone petroleum ether at 121-123°.
Eksempel 3: 6-metoksy-pseudo-tropin-a-cyklo-heksyl-glykolsyreester-hydroklorid: En blanding av 1,28 g 6-metoksy-pseudo-tropin og 3,9 g a-fenyl-a-cykloheksyl-glykolsyre- etylester blir oppvarmet med ca. 0,1 g natrium i 30 timer i vakuum (ca. Example 3: 6-methoxy-pseudo-tropine-α-cyclohexyl-glycolic acid ester hydrochloride: A mixture of 1.28 g of 6-methoxy-pseudo-tropine and 3.9 g of α-phenyl-α-cyclohexyl-glycolic acid ethyl ester is heated with approx. 0.1 g sodium for 30 hours in vacuum (approx.
1 mm Hg) til 110°, reaksjonsblandingen opptas etter avkjøling i 50 cm:! 2-n.saltsyre og ekstraheres med ialt 100 cm» eter. Det vandige saltsure lag blir rystet ut med ialt 300 cma kloroform, og kloroformekstrakten som er tørket over natriumsulfat, blir inndampet i vakuum. Resten oppløses i litt aceton, filtreres gjennom benkull, og hydrokloridet bringes til krystallisering ved tilsetning av eter. 6-metoksy-pseudo-tropin-a-fenyl-a-cykloheksyl-glykolsyreester-hydroklorid krystalliserer fra aceton/eter i krystaller med smp. 243—245° (sp.). 1 mm Hg) to 110°, the reaction mixture is taken up after cooling in 50 cm:! 2-n.hydrochloric acid and extracted with a total of 100 cm» of ether. The aqueous hydrochloric acid layer is shaken out with a total of 300 cm3 of chloroform, and the chloroform extract, which has been dried over sodium sulphate, is evaporated in vacuo. The residue is dissolved in a little acetone, filtered through bone charcoal, and the hydrochloride is brought to crystallisation by the addition of ether. 6-Methoxy-pseudo-tropine-α-phenyl-α-cyclohexyl-glycolic acid ester hydrochloride crystallizes from acetone/ether in crystals of m.p. 243—245° (sp.).
Eksempel 4: 6-metoksy-pseudo-tropin-fenyl-cyklo-heksyl-eddiksyreester-hydroklorid: En blanding av 3 g 6-metoksy-pseudo-tropin og 9,12 g fenyl-cykloheksyl-eddik-syre-etylester blir oppvarmet med ca. 0,1 g natriummetall i 30 timer i vakuum (ca. 1 mm Hg) til 130°, reaksionsblandingen opptas etter kjøling i 50 cm» 2-n.saltsyre og ekstraheres med ialt 150 cm» eter. Det vandige saltsure lag blir rystet ut med ialt 300 cm^ kloroform, og kloroformekstrakten som er tørket over natriumsulfat blir inndampet i vakuum. Resten løses i litt aceton, filtreres gjennom benkull, og hydro-kloridet bringes til å krystallisere ved tilsetning av eter. 6-metoksy-pseudo-tropin-fenyl-cykloheksyl-eddiksyreester-hydroklorid krystalliserer fra aceton/eter i krystaller med smp. 206—209° (sp.). Example 4: 6-methoxy-pseudo-tropine-phenyl-cyclohexyl-acetic acid ester hydrochloride: A mixture of 3 g of 6-methoxy-pseudo-tropine and 9.12 g of phenyl-cyclohexyl-acetic acid ethyl ester is heated with about. 0.1 g of sodium metal for 30 hours in vacuum (approx. 1 mm Hg) at 130°, the reaction mixture is taken up after cooling in 50 cm" of 2-n hydrochloric acid and extracted with a total of 150 cm" of ether. The aqueous hydrochloric acid layer is shaken out with a total of 300 cc of chloroform, and the chloroform extract, which has been dried over sodium sulfate, is evaporated in vacuo. The residue is dissolved in a little acetone, filtered through bone charcoal, and the hydrochloride is caused to crystallize by adding ether. 6-Methoxy-pseudo-tropine-phenyl-cyclohexyl-acetic acid ester hydrochloride crystallizes from acetone/ether in crystals of m.p. 206—209° (sp.).
Eksempel 5: 6-metoksy-pseudo-tropin-p-butoksy- bensosyreester-hydroklorid: En blanding av 2 g 6-metoksy-pseudo-tropin og 5,2 g p-butoksy-bensosyre-etylester blir oppvarmet med ca. 0,1 g natriummetall i 30 timer i vakuum (ca. 1 mm Hg) til 130°. Reaksionsblandingen opptas etter avkjøling i 50 cm» 2-n.saltsyre og ekstraheres med ialt 150 cm3 eter. Det vandige saltsure lag blir rystet ut med ialt 300 cm» kloroform, og kloroform-ekstrakten, som er tørket over natriumsulfat blir dampet inn i vakuum. Resten løses i litt aceton, filtreres gjennom benkull, og hydrokloridet bringes til å krystallisere ved tilsetning av eter. 6-metoksy-pseudo-tropin-p-butoksy-bensosyreester-hydroklorid krystalliserer fra aceton/eter i krystaller med smp. 197 —199° (sp.). Example 5: 6-methoxy-pseudo-tropine-p-butoxy- Benzoic acid ester hydrochloride: A mixture of 2 g of 6-methoxy-pseudo-tropine and 5.2 g of p-butoxy-benzoic acid ethyl ester is heated with approx. 0.1 g of sodium metal for 30 hours in vacuum (about 1 mm Hg) at 130°. After cooling, the reaction mixture is taken up in 50 cm3 of 2-n hydrochloric acid and extracted with a total of 150 cm3 of ether. The aqueous hydrochloric acid layer is shaken out with a total of 300 cm" of chloroform, and the chloroform extract, which has been dried over sodium sulfate, is evaporated in vacuo. The residue is dissolved in a little acetone, filtered through bone charcoal, and the hydrochloride is caused to crystallize by the addition of ether. 6-Methoxy-pseudo-tropine-p-butoxy-benzoic acid ester hydrochloride crystallizes from acetone/ether in crystals of m.p. 197 —199° (sp.).
Eksempel 6: 6-metoksy-pseudo-tropin-o-fenoksy- bensosyreester-hydroklorid: En blanding av 3 g 6-metoksy-pseudo-tropin og 8,5 g o-fenoksy-bensosyre- etylester blir oppvarmet med ca. 0,1 g natriummetall i 30 timer i vakuum (ca. 1 mm Hg) til 130°. Reaksjonsblandingen blir etter avkjøling opptatt i 50 cm3 2-n.saltsyre og ekstrahert med ialt 150 ems eter. Det vandige saltsure lag blir rystet ut med ialt 300 ems kloroform, og kloroformekstrakten, som er tørket over natriumsulfat blir inndampet i vakuum. Resten oppløses i litt etanol, filtreres gjennom benkull, og hydro-kloridet blir brakt til å krystallisere ved tilsetning av eter. 6-metoksy-pseudo-tropin-o-fenoksy-bensosyreester-hydro-klorid krystalliserer fra etanol/eter i krystaller med sm.p. 228—229° (sp.). Example 6: 6-methoxy-pseudo-tropine-o-phenoxy- Benzoic acid ester hydrochloride: A mixture of 3 g of 6-methoxy-pseudo-tropine and 8.5 g of o-phenoxy-benzoic acid ethyl ester is heated with approx. 0.1 g of sodium metal for 30 hours in vacuum (about 1 mm Hg) at 130°. After cooling, the reaction mixture is taken up in 50 cm3 of 2-n hydrochloric acid and extracted with a total of 150 ems of ether. The aqueous hydrochloric acid layer is shaken out with a total of 300 ems chloroform, and the chloroform extract, which has been dried over sodium sulphate, is evaporated in vacuo. The residue is dissolved in a little ethanol, filtered through bone charcoal, and the hydrochloride is brought to crystallize by the addition of ether. 6-Methoxy-pseudo-tropine-o-phenoxy-benzoic acid ester hydrochloride crystallizes from ethanol/ether in crystals of m.p. 228—229° (sp.).
Eksempel 7: 6-metoksy-pseudo-tropin-fluoren-9- karbonsyreester-hydroklorid: En blanding av 3 g 6-metoksy-pseudo-tropin og 8,3 g fluoren-9-karbonsyre-etylester blir oppvarmet med ca. 0,1 g natriummetall i 30 timer i vakuum (ca. 1 mm Hg) til 130°, reaksjonsblandingen blir etter av-kjøling opptatt i 50 cm?> 2-n.saltsyre og ekstrahert med ialt 150 cm3 eter. Det vandige saltsure lag blir rystet ut med ialt 300 ems kloroform, og kloroformekstrakten som er tørket over natriumsulfat blir dampet inn i vakuum. Resten løses i litt aceton, filtreres gjennom benkull, og hydrokloridet bringes til å krystallisere ved tilsetning av eter. 6-metoksy-pseudo- tropin-fluoren-9-karbonsyreester-hydroklorid krystalliserer fra aceton/eter i krystaller med smp. 215 —217° (sp.). Example 7: 6-methoxy-pseudo-tropine-fluorene-9- carboxylic acid ester hydrochloride: A mixture of 3 g of 6-methoxy-pseudo-tropine and 8.3 g of fluorene-9-carboxylic acid ethyl ester is heated with approx. 0.1 g of sodium metal for 30 hours in a vacuum (approx. 1 mm Hg) at 130°, the reaction mixture is, after cooling, taken up in 50 cm?> 2-n hydrochloric acid and extracted with a total of 150 cm 3 of ether. The aqueous hydrochloric acid layer is shaken out with a total of 300 ems of chloroform, and the chloroform extract which has been dried over sodium sulphate is evaporated in vacuo. The residue is dissolved in a little acetone, filtered through bone charcoal, and the hydrochloride is caused to crystallize by the addition of ether. 6-Methoxy-pseudo-tropine-fluorene-9-carboxylic acid ester hydrochloride crystallizes from acetone/ether in crystals with m.p. 215 —217° (sp.).
Eksempel 8: 6-metoksy-pseudo-tropin-xanten-9- karbonsyreester-hydroklorid: En blanding av 3 g 6-metoksy-pseudo-tropin og 8,4 g xanten-9-karbonsyre-metyl-ester blir oppvarmet med ca. 0,1 g natriummetall i 30 timer i vakuum (ca. 1 mm Hg) til 130°. Reaksjonsblandingen opptas etter avkjøling i 60 ems 2-n.saltsyre og ekstraheres med ialt 160 cm» eter. Det vandige saltsure lag blir rystet ut med ialt 300 cm« kloroform, og kloroformekstrakten som er tørket over natriumsulfat blir inndampet i vakuum. Resten blir løst i litt metanol, filtrert gjennom benkull, og hydrokloridet blir brakt til å krystallisere ved tilsetning av eter, 6-metoksy-pseudo-tropin-xanten-9-kartaonsyreesterhydro-klorid krystalliserer fra metanol/eter i krystaller med smp. 208—211° (sp.). Example 8: 6-methoxy-pseudo-tropine-xanthene-9- carboxylic acid ester hydrochloride: A mixture of 3 g of 6-methoxy-pseudo-tropine and 8.4 g of xanthene-9-carboxylic acid methyl ester is heated with approx. 0.1 g of sodium metal for 30 hours in vacuum (about 1 mm Hg) at 130°. After cooling, the reaction mixture is taken up in 60 ems of 2-n hydrochloric acid and extracted with a total of 160 cm" of ether. The aqueous hydrochloric acid layer is shaken out with a total of 300 cc of chloroform, and the chloroform extract, which has been dried over sodium sulphate, is evaporated in vacuo. The residue is dissolved in a little methanol, filtered through bone charcoal, and the hydrochloride is brought to crystallize by the addition of ether, 6-methoxy-pseudo-tropine-xanthene-9-cartaonic acid ester hydrochloride crystallizes from methanol/ether in crystals of m.p. 208—211° (sp.).
Eksempel 9: 6-etoksy-tropin-p-butoksy-benso syreester-hydroklorid: 5 g 6-etoksy-tropinon-hydroklorid blir hydrert i 50 cm3 abs etanol i autoklav med Raneynikkel i 5 timer ved 40—45° og 60 at. Man filtrerer fra katalysatoren og destillerer alkoholen av i svakt vakuum. Den oljeaktige rest blir opptatt i 10 ems vann, gjort alkalisk med mettet soda-oppløsning, mettet med koksalt, og 6-etoksy-tropinet ekstrahert med ialt 60 cm3 kloroform. Etter tørking over natriumsulfat og avdestillering av kloroformen blir resten destillert i høyvakuum. Kp. 106° ved 0,7 mm Hg. Example 9: 6-ethoxy-tropine-p-butoxy-benzo acid ester hydrochloride: 5 g of 6-ethoxytropinone hydrochloride is hydrated in 50 cm3 of absolute ethanol in an autoclave with Raney nickel for 5 hours at 40-45° and 60 at. The catalyst is filtered and the alcohol is distilled off in a weak vacuum. The oily residue is taken up in 10 ems of water, made alkaline with saturated soda solution, saturated with common salt, and the 6-ethoxytropine extracted with a total of 60 cm3 of chloroform. After drying over sodium sulphate and distilling off the chloroform, the residue is distilled under high vacuum. Kp. 106° at 0.7 mm Hg.
En blanding av 3 g 6-etoksy-tropin og 7,27 g p-butoksy-bensosyre-etyleter blir oppvarmet med ca. 0,1 g natriummetall i 30 timer i vakuum (ca. 1 mm Hg) til 130°. Reaksjonsbehandlingen opptas etter av-kjøling i 50 ems 2-n.saltsyre og ekstraheres med i alt 150 cm3 eter. Det vanlige saltsure lag blir rystet ut med ialt 300 cm3 kloroform, og kloroform-ekstrakten som er tørket over natriumsulfat blir inndampet i vakuum. Resten løses i litt aceton, filtreres gjennom benkull, og hydrokloridet bringes til å krystallisere ved tilsetning av eter. 6-etoksy-tropin- p-butoksybensosyre-ester-hydroklorid krystalliserer fra aceton/ eter med smp 188—190° (sp). A mixture of 3 g of 6-ethoxytropine and 7.27 g of p-butoxy-benzoic acid ethyl ether is heated with approx. 0.1 g of sodium metal for 30 hours in vacuum (about 1 mm Hg) at 130°. The reaction treatment is taken up after cooling in 50 ems 2-n hydrochloric acid and extracted with a total of 150 cm3 of ether. The normal hydrochloric acid layer is shaken out with a total of 300 cm3 of chloroform, and the chloroform extract, which has been dried over sodium sulphate, is evaporated in vacuum. The residue is dissolved in a little acetone, filtered through bone charcoal, and the hydrochloride is caused to crystallize by the addition of ether. 6-Ethoxytropine p-butoxybenzoic acid ester hydrochloride crystallizes from acetone/ether with m.p. 188-190° (sp).
Eksempel 10: 6-etoksy-tropin-o-fenoksy-bensosyreester-hydroklorid: En blanding av 4 g 6-etoksy-tropin og 10,97 g o-fenoksybensosyre-etylester blir oppvarmet med 0,1 g natriummetall i 30 timer i vakuum (ca. 1 mm Hg) til 130°, reaksjonsblandingen blir etter avkjøling opptatt i 50 ems 2-n.saltsyre og ekstrahert med ialt 150 cm3 eter. Det vandige saltsure lag blir rystet ut med ialt 300 ems kloroform, og kloroformekstrakten som er tørket over natriumsulfat blir inndampet i vakuum. Resten blir løst i litt etanol, filtrert gjennom benkull, og hydrokloridet blir brakt til å krystallisere ved tilsetning av eter. 6-etoksy-tropin-o-fenoksy-bensosyreester-hydroklorid krysetalliserer fra etanol/eter i krystaller med smp. 174— 175° (sp).... Eksempel 11: 6-etoksy-tropin-f luoren-9-kar- bonsyreester-hydroklorid: En blanding av 3 g 6-etoksy-tropin og 7,7 g fluoren-9-karbonsyreetylester blir opvarmet med ca. 0,1 g natriummetall i 30 timer i vakuum (ca. 1 mm Hg) til 110°, reaksjonsblandingen blir etter avkjøling opptatt i 50 ems 2-n.saltsyre og ekstrahert med ialt 150 cm3 eter. Det vandige saltsure lag blir rystet ut med ialt 300 cm3 kloroform, og kloroformekstrakten som er tørket over natriumsulfat blir inndampet i vakuum. Resten løses i litt aceton, filtreres gjennom benkull, og hydrokloridet bringes til å krystallisere ved tilsetning av litt eter. 6-etoksy-tropinfluoren-9-karbon-syreester-hydroklorid krystalliserer fra aceton/eter i krystaller med smp 169—172° Example 10: 6-ethoxy-tropine-o-phenoxy-benzoic acid ester hydrochloride: A mixture of 4 g of 6-ethoxy-tropine and 10.97 g of o-phenoxy-benzoic acid ethyl ester is heated with 0.1 g of sodium metal for 30 hours in vacuum (approx. 1 mm Hg) to 130°, the reaction mixture is, after cooling, taken up in 50 ems of 2-n hydrochloric acid and extracted with a total of 150 cm3 of ether. The aqueous hydrochloric acid layer is shaken out with a total of 300 ems chloroform, and the chloroform extract which has been dried over sodium sulphate is evaporated in vacuo. The residue is dissolved in a little ethanol, filtered through bone charcoal, and the hydrochloride is brought to crystallize by the addition of ether. 6-Ethoxy-tropine-o-phenoxy-benzoic acid ester hydrochloride crystallises from ethanol/ether in crystals with m.p. 174— 175° (sp).... Example 11: 6-ethoxy-tropine-fluorene-9-car- boronic acid ester hydrochloride: A mixture of 3 g of 6-ethoxytropine and 7.7 g of fluorene-9-carboxylic acid ethyl ester is heated with approx. 0.1 g of sodium metal for 30 hours in a vacuum (approx. 1 mm Hg) at 110°, the reaction mixture is, after cooling, taken up in 50 ems of 2-n.hydrochloric acid and extracted with a total of 150 cm3 of ether. The aqueous hydrochloric acid layer is shaken out with a total of 300 cm3 of chloroform, and the chloroform extract, which has been dried over sodium sulfate, is evaporated in vacuo. The residue is dissolved in a little acetone, filtered through bone charcoal, and the hydrochloride is caused to crystallize by adding a little ether. 6-Ethoxytropinefluorene-9-carbon acid ester hydrochloride crystallizes from acetone/ether in crystals with mp 169-172°
(sp). (sp).
Eksempel 12: 6-etoksy-tropin-xanten-9-karbon- syreester-hydroklorid: En blanding av 3 g 6-etoksy-tropin og 7,7 g xanten-9-karbonsyremetylester blir oppvarmet med ca. 0,1 g natriummetall i 30 timer i vakuum (ca. 1 mm Hg) til 130°. Reaksjonsblandingen opptas etter avkjøl-ing i 60 cm3 2-n.saltsyre og ekstraheres med i alt 160 ems eter. Det vandige saltsure lag blir rystet ut med ialt 300 cm« kloroform, og kloroformekstrakten som er tørket over natriumsulfat blir inndampet 1 vakuum. Resten blir løst i litt etanol, filtrert gjennom benkull, og hydro-kloridet blir brakt til å krystallisere ved tilsetning av eter. 6-etoksy-tropin-xanten-9-karbon-syreester-hydroklorid krystalliserer fra aceton/eter i krystaller med smp. -235— 237° (sp). Example 12: 6-ethoxy-tropine-xanthene-9-carbon- acid ester hydrochloride: A mixture of 3 g of 6-ethoxytropine and 7.7 g of xanthene-9-carboxylic acid methyl ester is heated with approx. 0.1 g of sodium metal for 30 hours in vacuum (about 1 mm Hg) at 130°. After cooling, the reaction mixture is taken up in 60 cm3 of 2N hydrochloric acid and extracted with a total of 160 ems of ether. The aqueous hydrochloric acid layer is shaken out with a total of 300 cc of chloroform, and the chloroform extract which has been dried over sodium sulphate is evaporated under vacuum. The residue is dissolved in a little ethanol, filtered through bone charcoal, and the hydrochloride is brought to crystallize by the addition of ether. 6-Ethoxy-tropine-xanthene-9-carbon acid ester hydrochloride crystallizes from acetone/ether in crystals with m.p. -235— 237° (sp).
Eksempel 13: 6-etoksy-pseudo-tropin-fenyl-cyklohek- syl-eddiksyreester-hydroklorid: Til en kokende oppløsning av 130,7 g 6-etoksytropinon i 1400 cm3 abs. etanol blir det porsjonsvis og under røring i løpet, av 2 timer satt 130 g natrium. Reaksjonsblandingen destilleres med vanndamp, destil-lasjonsresten mettes med koksalt og ekstraheres med ialt 600 ems kloroform. Kloroformekstrakten som er tørket over natriumsulfat blir inndampet i vakuum, og resten destillert i høyvakuum, hvorved 6-etoksypseudo-tropin går over ved 0,8 mm Hg ved 123—131° og stivner i forlaget. Smp 76—78° etter omkrystallisering fra aceton/petroleter. Example 13: 6-ethoxy-pseudo-tropine-phenyl-cyclohex- Syl-acetic acid ester hydrochloride: To a boiling solution of 130.7 g of 6-ethoxytropinone in 1400 cm3 abs. of ethanol, 130 g of sodium are added in portions and with stirring over the course of 2 hours. The reaction mixture is distilled with steam, the distillation residue is saturated with common salt and extracted with a total of 600 ems chloroform. The chloroform extract which is dried over sodium sulphate is evaporated in vacuo, and the residue distilled in high vacuum, whereby 6-ethoxypseudo-tropine passes over at 0.8 mm Hg at 123-131° and solidifies in the precursor. Mp 76-78° after recrystallization from acetone/petroleum ether.
En blanding av 3 g 6-etoksy-pseudo-tropin og 8,5 g fenyl-cyklo-heksyl-eddik-syre-etylester blir oppvarmet med ca. 0,1 g natriummetall i 30 timer i vakuum (ca. A mixture of 3 g of 6-ethoxy-pseudo-tropine and 8.5 g of phenyl-cyclo-hexyl-acetic acid ethyl ester is heated with approx. 0.1 g of sodium metal for 30 hours in a vacuum (approx.
1 mm Hg) til 130°. Reaksjonsblandingen blir etter avkjøling opptatt i 50 cm3 2-n.-saltsyre og ekstrahert med ialt 150 cm3 eter. Det vandige saltsure lag blir rystet ut med ialt 300 cm3 kloroform, og kloroform-ekstrakten som er tørket over natriumsulfat blir inndampet i vakuum. Resten blir oppløst i litt aceton, filtrert gjennom . benkull, og hydrokloridet blir brakt til å krystallisere ved tilsetning av eter. 6-etoksy-pseudo-tropin-fenyl-cykloheksyl-edikk-syreester-hydroklorid krystalliserer fra aceton/eter i krystaller med smp 194— 196° (sp). 1 mm Hg) to 130°. After cooling, the reaction mixture is taken up in 50 cm3 of 2-n hydrochloric acid and extracted with a total of 150 cm3 of ether. The aqueous hydrochloric acid layer is shaken out with a total of 300 cm3 of chloroform, and the chloroform extract, which has been dried over sodium sulphate, is evaporated in vacuo. The residue is dissolved in a little acetone, filtered through . bone charcoal, and the hydrochloride is brought to crystallize by the addition of ether. 6-Ethoxy-pseudo-tropine-phenyl-cyclohexyl-acetic acid ester hydrochloride crystallizes from acetone/ether in crystals with mp 194-196° (sp).
Eksempel 14: 6-etoksy-pseudo-tropin-etoksy-difenyl- edikksyreester-hydroklorid: En. blanding av 2 g 6-etoksy-pseudo-tropin og 6,14 g etoksy-difenyl-edikksyre-etylester blir oppvarmet med ca. 0,1 g natriummetall i 30 timer i vakuum (ca. 1 mm Hg) til 110°. Reaksjonsblandingen blir etter avkjøling opptatt i 50 cm3 2-n.saltsyre og ekstrahert med ialt 160 cm3 eter. Det vandige saltsure lag blir rystet ut med ialt 350 cm3 kloroform, og kloroformekstrakten som er tørket over natriumsulfat blir inndampet i vakuum. Resten løses i litt aceton, filtreres gjennom benkull, og hydrokloridet bringes til å krystallisera ved tilsetning av eter. 6-etoksy-pseudo-tropin- etoksydifenyl-edikksyreester-hydroklorid krystalliserer fra aceton/eter i krystaller med smp 164—166° (sp). Example 14: 6-ethoxy-pseudo-tropine-ethoxy-diphenyl- Acetic acid ester hydrochloride: One. mixture of 2 g of 6-ethoxy-pseudo-tropine and 6.14 g of ethoxy-diphenyl-acetic acid ethyl ester is heated with approx. 0.1 g of sodium metal for 30 hours in vacuum (about 1 mm Hg) at 110°. After cooling, the reaction mixture is taken up in 50 cm3 of 2-n hydrochloric acid and extracted with a total of 160 cm3 of ether. The aqueous hydrochloric acid layer is shaken out with a total of 350 cm3 of chloroform, and the chloroform extract which has been dried over sodium sulfate is evaporated in vacuo. The residue is dissolved in a little acetone, filtered through bone charcoal, and the hydrochloride is caused to crystallize by the addition of ether. 6-ethoxy-pseudo-tropine- ethoxydiphenyl acetic acid ester hydrochloride crystallizes from acetone/ether in crystals of mp 164-166° (sp).
Eksempel 15: 6-etoksy-pseudo-tropin-a-fenyl-a- cykloheksyl-glykolsyre-ester: En blanding av 3 g 6-etoksy-pseudo-tropin og 8,5 g a-fenyl-a-cykloheksyl-glykolsyre-etylester blir oppvarmet med ca. 0,1 g natriummetall i 30 timer i vakuum (ca. 1 mm Hg) til 130°. Reaksjonsblandingen opptas etter avkjøling i 50 cm3 2-n.-saltsyre og ekstraheres med ialt 150 cm3 eter. Det vandige saltsure lag blir underlagt (unterschichtet) med 100 cm- kloroform, under iskjøling tilsatt med mettet sodaoppløsning inntil svak fenolftaleinal kalisk reaksjon, og ekstrahert med ialt 300 cm3 kloroform. De samlete kloroformekstrakter som er tørket over natriumsulfat etterlater ved inndamping i vakuum Example 15: 6-ethoxy-pseudo-tropine-α-phenyl-α- cyclohexyl-glycolic acid ester: A mixture of 3 g of 6-ethoxy-pseudo-tropine and 8.5 g of α-phenyl-α-cyclohexyl-glycolic acid ethyl ester is heated with approx. 0.1 g of sodium metal for 30 hours in vacuum (about 1 mm Hg) at 130°. After cooling, the reaction mixture is taken up in 50 cm3 of 2-n hydrochloric acid and extracted with a total of 150 cm3 of ether. The aqueous hydrochloric acid layer is underlaid (unterschichtet) with 100 cm chloroform, under ice-cooling added with saturated soda solution until weak phenolphthalein calic reaction, and extracted with a total of 300 cm3 of chloroform. The collected chloroform extracts, which are dried over sodium sulfate, leave behind by evaporation in vacuo
6-etoksy-pseudo-tropin-a-fenyl-a-cyklo-heksyl-glykolsyreestér. 6-ethoxy-pseudo-tropine-α-phenyl-α-cyclohexyl-glycolic acid ester.
Eksempel 16: 6-etoksy-pseudo-tropin-p-butoksy- bensosyreester-hydroklorid: En blanding av 3 g 6-etoksy-pseudo-tropin og 7,27 g p-butoksy-bensosyre-etylester blir oppvarmet med ca. 0,1 g natriummetall i 30 timer i vakuum (ca. 1 mm Hg) til 130°. Reaksjonsblandingen blir etter av-kjølingen opptatt i 50 cm3 2-n.saltsyre og ekstrahert med ialt 150 cm3 eter. Det vandige saltsure lag blir rystet ut med ialt 300 cm^kloroform, og kloroformekstrakten som er tørket over natriumsulfat blir inndampet i vakuum. Resten løses i litt etanol, filtreres gjennom benkull, og hydrokloridet bringes til å krystallisere ved tilsetning av eter. 6-etoksy-pseudo-tropin-p-butoksy-benso-syreester-hydroklorid krystalliserer fra etanol/eter i krystaller med smp. 178— 180° (sp). Example 16: 6-ethoxy-pseudo-tropine-p-butoxy- Benzoic acid ester hydrochloride: A mixture of 3 g of 6-ethoxy-pseudo-tropine and 7.27 g of p-butoxy-benzoic acid ethyl ester is heated with approx. 0.1 g of sodium metal for 30 hours in vacuum (about 1 mm Hg) at 130°. After cooling, the reaction mixture is taken up in 50 cm3 of 2N hydrochloric acid and extracted with a total of 150 cm3 of ether. The aqueous hydrochloric acid layer is shaken out with a total of 300 cc of chloroform, and the chloroform extract, which has been dried over sodium sulfate, is evaporated in vacuo. The residue is dissolved in a little ethanol, filtered through bone charcoal, and the hydrochloride is caused to crystallize by adding ether. 6-Ethoxy-pseudo-tropine-p-butoxy-benzoic acid ester hydrochloride crystallizes from ethanol/ether in crystals of m.p. 178— 180° (sp).
Eksempel 17: 6-etoksy-pseudo-tropin-fluoren-9- karbonsyreester-hydroklorid: En blanding av 3 g 6-etoksy-pseudo-tropin og 7,72 g fluoren-9-karbonsyre-etylester blir varmet med ca. 0,1 g natri-ummetal i 30 timer i vakuum (ca. 1 mm Hg) til 110—115°. Reaksjonsblandingen blir etter avkjøling opptatt i 50 cm3 2-n.-saltsyre og ekstrahert med ialt 150 cm3 eter. Det vandige saltsure lag blir rystet ut med ialt 300 cm3 kloroform, og kloroformekstrakten som er tørket over natriumsulfat blir inndampet i vakuum. Resten løses i litt aceton, filtreres gjennom benkull, og hydrokloridet bringes til å krystallisere ved tilsetning av eter. 6-etoksy-pseudo-tropin-fluoren-9-karbonsyreester-hydroklorid krystalliserer fra aceton/eter i krystaller med smp 236—238° (sp). Example 17: 6-ethoxy-pseudo-tropine-fluorene-9- carboxylic acid ester hydrochloride: A mixture of 3 g of 6-ethoxy-pseudo-tropine and 7.72 g of fluorene-9-carboxylic acid ethyl ester is heated with approx. 0.1 g of sodium metal for 30 hours in vacuum (approx. 1 mm Hg) at 110-115°. After cooling, the reaction mixture is taken up in 50 cm3 of 2-n hydrochloric acid and extracted with a total of 150 cm3 of ether. The aqueous hydrochloric acid layer is shaken out with a total of 300 cm3 of chloroform, and the chloroform extract, which has been dried over sodium sulfate, is evaporated in vacuo. The residue is dissolved in a little acetone, filtered through bone charcoal, and the hydrochloride is caused to crystallize by the addition of ether. 6-ethoxy-pseudo-tropine-fluorene-9-carboxylic acid ester hydrochloride crystallizes from acetone/ether in crystals of mp 236-238° (sp).
Eksempel 18: 6-etoksy-pseudo-tropin-xanten-9- karbonsyreester-hydroklorid: En blanding av 3 g 6-etoksy-pseudo-tropin og 7,7 g xanten-9-karbonsyre-mety-lester blir varmet med ca. 0,1 g natriurh-metal i 30 timer i vakuum (ca. 1 mm Hg) til 130°. Reaksjonsblandingen blir etter av-kjøling opptatt i 60 cm3 2-n.saltsyre og ekstrahert med ialt 160 ems eter. Det vandige saltsure lag blir rystet ut med i alt 300 cm» kloroform, og kloroformekstrakten som er tørket over natriumsulfat blir "inndampet i vakuum. Resten løses i litt etanol, filtreres gjennom benkull, og hydrokloridet bringes til å krystallisere ved tilsetning av eter. 6-etoksypseudo-tropin- xanten-9-karbonsyreester-hydroklorid krystalliserer fra etanol/eter i krystaller med smp 237—239° (sp). Example 18: 6-ethoxy-pseudo-tropine-xanthene-9- carboxylic acid ester hydrochloride: A mixture of 3 g of 6-ethoxy-pseudo-tropine and 7.7 g of xanthene-9-carboxylic acid methyl ester is heated with approx. 0.1 g of sodium metal for 30 hours in vacuum (about 1 mm Hg) at 130°. After cooling, the reaction mixture is taken up in 60 cm3 of 2N hydrochloric acid and extracted with a total of 160 ems of ether. The aqueous hydrochloric acid layer is shaken out with a total of 300 cm" of chloroform, and the chloroform extract, which has been dried over sodium sulfate, is "evaporated in vacuo. The residue is dissolved in a little ethanol, filtered through charcoal, and the hydrochloride is caused to crystallize by the addition of ether. 6 -ethoxypseudo-tropine- xanthene-9-carboxylic acid ester hydrochloride crystallizes from ethanol/ether in crystals with mp 237-239° (sp).
Eksempel 19: N-oksyetyl-6-metoksy-nortropin- dibensosyreester-hydroklorid: 15 g n-oksyetyl-6-metoksy-nortropin blir hydrert i 50 cm3 abs metanol i autoklav med Raneynikkel i 5 timer ved 45° og et begynnelsestrykk på 60 at. Han krystalliserer av fra katalysatoren, damper metanolen av under nedsatt trykk og destillerer resten i høyvakuum. Kokepunktet for n-oksetyl-6-metoksy-nortropin er 115— 125° ved 0,08 mm Hg. En blanding av 4 g n-oksyetyl-6-metoksy-:nortropin og 8,9 g bensosyreetylester blir varmet med ca. 0,2 g natriummetall i 30 timer i vakuum (ca. 1 mm Hg) til 125—130°. Reaksjonsblandingen opptas etter avkjøling i 50 ems 2-n. saltsyre og ekstraheres med ialt 240 ems eter. Det vandige saltsure lag blir rystet ut med ialt 300 cm3 kloroform, og kloroform-ekstrakten som er tørket over natriumsulfat blir inndampet i vakuum. Resten løses i litt metanol, filtreres gjennom benkull, og hydrokloridet bringes til å krystallisere ved tilsetning av eter. N-oksyetyl-6-metoksy-nortropin-dibensosyreester-hyd-klorid krystalliserer fra metanol/eter i krystaller med smp 163—166° (sp). Example 19: N-oxyethyl-6-methoxy-nortropin- dibenzoic acid ester hydrochloride: 15 g of n-oxyethyl-6-methoxy-nortropine is hydrated in 50 cm3 abs methanol in an autoclave with Raney nickel for 5 hours at 45° and an initial pressure of 60 at. He crystallizes it from the catalyst, evaporates the methanol under reduced pressure and distills the remainder under high vacuum. The boiling point of n-oxetyl-6-methoxy-nortropine is 115-125° at 0.08 mm Hg. A mixture of 4 g of n-oxyethyl-6-methoxy-nortropine and 8.9 g of benzoic acid ethyl ester is heated with approx. 0.2 g of sodium metal for 30 hours in vacuum (approx. 1 mm Hg) at 125-130°. The reaction mixture is taken up after cooling in 50 ems 2-n. hydrochloric acid and extracted with a total of 240 ems of ether. The aqueous hydrochloric acid layer is shaken out with a total of 300 cm3 of chloroform, and the chloroform extract, which has been dried over sodium sulphate, is evaporated in vacuo. The residue is dissolved in a little methanol, filtered through bone charcoal, and the hydrochloride is caused to crystallize by adding ether. N-oxyethyl-6-methoxy-nortropine dibenzoic acid ester hydrochloride crystallizes from methanol/ether in crystals with mp 163-166° (sp).
Eksempel 20: 6-metoksy-pseudo-tropin- bensilsyreester: Framstillingen av denne ester ved alkoholyse av bensilsyre-etylester er beskrevet i Eksempel 2. Under henvisning til dette stoff skal det nå som eksempel be-skrives acyléring av et 6-alkoksy-tropinderivat med et syreklorid: a) En oppløsning av 3 g 6-metoksy-pseudo-tropin og 2,31 g difenyl-klor-edikk-syre-klorid i 100 cm» bensol blir varmet i 24 timer med tilbakeløp til 80—85°. Reak-sjonsoppløsningen blir etter avkjøling ekstrahert med ialt 200 cm» 2-n.saltsyre, og det vandige saltsure lag blir rystet ut med ialt 300 cm3 kloroform. De samlete kloroformuttrekk som er tørket over natriumsulfat etterlater etter inndamping i vakuum 6-metoksy-pseudo-tropinbensil-syreester-hydroklorid som for ytterligere rensing overføres via den frie ester til hydrobromidet som krystalliserer lett. 6-metoksy-pseudo-tropin-bensilsyreester-hydrobromid har etter omkrystallisering fra metanol/eter et smp på 226— 228° (sp). b) En blanding av 2,1 g 6-metoksy-pseudo-propin og 2,7 g difenyl-klor-edikk-syre-klorid blir varmet i 2 timer til 100°. Reaksjonsblandingen blir heldt i isvann, den saltsure vandige oppløsning blir rystet ut med ialt 200 cm3 eter, og det vandige saltsure lag blir ekstrahert med" ialt 200 cm3 kloroform. De samlete kloroformuttrekk som er tørket over natriumsulfat etterlater etter inndamping i vakuum 6-metoksy-pseudo-tropinhydroklorid som er identisk med det stoff som er oppnådd i henhold til eksempel 2. Example 20: 6-methoxy-pseudo-tropine- Benzyl acid ester: The production of this ester by alcoholysis of benzyl acid ethyl ester is described in Example 2. With reference to this substance, the acylation of a 6-alkoxy-tropine derivative with an acid chloride will now be described as an example: a) A solution of 3 g 6-Methoxy-pseudo-tropine and 2.31 g of diphenyl-chloro-acetic acid chloride in 100 cm" of benzene are heated for 24 hours at reflux to 80-85°. After cooling, the reaction solution is extracted with a total of 200 cm3 of 2N hydrochloric acid, and the aqueous hydrochloric acid layer is shaken off with a total of 300 cm3 of chloroform. The combined chloroform extracts which have been dried over sodium sulphate leave after evaporation in vacuo 6-methoxy-pseudo-tropine benzyl acid ester hydrochloride which for further purification is transferred via the free ester to the hydrobromide which crystallizes easily. 6-Methoxy-pseudo-tropine-benzyl acid ester hydrobromide has, after recrystallization from methanol/ether, a m.p. of 226-228° (sp). b) A mixture of 2.1 g of 6-methoxy-pseudo-propyne and 2.7 g of diphenyl-chloro-acetic acid chloride is heated for 2 hours to 100°. The reaction mixture is poured into ice water, the hydrochloric acid aqueous solution is shaken out with a total of 200 cm3 of ether, and the aqueous hydrochloric acid layer is extracted with a total of 200 cm3 of chloroform. The combined chloroform extracts, which are dried over sodium sulfate, leave after evaporation in vacuo 6-methoxy- pseudo-tropine hydrochloride which is identical to the substance obtained according to Example 2.
Eksempel 21: Example 21:
6-metoksy-tropin-bensilsyreester: 6-Methoxytropine Benzyl Ester:
En blanding av 7,29 g 6-metoksy-tropin og 21,9 g bensilsyreetylester blir varmet med 0,2 g natriummetall i 30 timer i vakuum (ca. 2 mm Hg) til 125—130°. Til å begynne med blir det en sterk blære- og skumdannelse på grunn av etanol som destillerer av, men dette opphører fullstendig mot slutten. Etter avkjøling blir. reaksjonsblandingen opptatt i 80 ems 2-n.saltsyre og ekstrahert med ialt 200 cm3 eter. Det vandige saltsure lag blir gjort alkalisk med 25 pst. ammoniumhydroksydoppløs-ning. Den 6-metoksy-tropin-bensilsyreester som oppnås blir ekstrahert med til sammen 300 cm3 kloroform, de samlete kloroformekstrakter blir tørket over natriumsulfat, og kloroformen destilleres av. Etter en kort stunds henstand krystalliserer resten gjennom. Smp. 98—100°. Etter omkrystallisering fra bensol/petroleter og bensol alene smelter 6-metoksy-tropin-bensilsyreester, C2,,H2704N, ved 99—101°. A mixture of 7.29 g of 6-methoxytropine and 21.9 g of benzylic acid ethyl ester is heated with 0.2 g of sodium metal for 30 hours in vacuum (about 2 mm Hg) to 125-130°. At first there is a strong bubbling and foaming due to ethanol distilling off, but this ceases completely towards the end. After cooling becomes. the reaction mixture taken up in 80 ems of 2-n hydrochloric acid and extracted with a total of 200 cm3 of ether. The aqueous hydrochloric acid layer is made alkaline with 25% ammonium hydroxide solution. The 6-methoxytropine benzylic acid ester which is obtained is extracted with a total of 300 cm 3 of chloroform, the collected chloroform extracts are dried over sodium sulfate, and the chloroform is distilled off. After a short delay, the rest crystallizes through. Temp. 98—100°. After recrystallization from benzene/petroleum ether and benzene alone, 6-methoxytropine benzylic acid ester, C2,,H2704N, melts at 99-101°.
6-metoksy-tropin-bensilsyreester-hydroklorid, smp 146—148° fra metanol/eter. 6-Methoxytropine benzyl ester hydrochloride, mp 146-148° from methanol/ether.
6-metoksy-tropin-bensilsyreester-hyd-robromid, smp 197—199° fra metanol/ eter. 6-Methoxytropine benzyl ester hydrobromide, mp 197-199° from methanol/ether.
Eksempel 22: Example 22:
6-metoksy-tropin-bensosyreester: 6-Methoxy-tropine benzoic acid ester:
En blanding av 16,6 g 6-metoksytropin og 29,1 g bensosyre-etylester blir varmet med 0,3 g natrium i 30 timer i vakuum (ca. 10 mm Hg) til 125—i30°. Til å begynne med er det en sterk skumdannelse på grunn av etanol som destillerer av, men mot slutten av reaksjonstiden hører denne fullstendig opp. Etter avkjøling blir reaksjonsblandingen løst i 150 ems 2-n.saltsyre og ekstrahert med ialt 90 cm3 eter. Den vandige saltsure oppløsning blir derpå gjort alkalisk med 25 pst. ammonium-hydroksydoppløsning og rystet ut med ialt 400 cm3 kloroform. De samlete kloroformekstrakter blir tørket over natriumsulfat og kloroformen destillert av i svakt vakuum. A mixture of 16.6 g of 6-methoxytropin and 29.1 g of benzoic acid ethyl ester is heated with 0.3 g of sodium for 30 hours in vacuum (about 10 mm Hg) to 125-130°. At first there is a strong foam formation due to ethanol distilling off, but towards the end of the reaction time this stops completely. After cooling, the reaction mixture is dissolved in 150 ems of 2-n hydrochloric acid and extracted with a total of 90 cm3 of ether. The aqueous hydrochloric acid solution is then made alkaline with 25% ammonium hydroxide solution and shaken out with a total of 400 cm3 of chloroform. The collected chloroform extracts are dried over sodium sulphate and the chloroform is distilled off in a weak vacuum.
6-metoksy-tropin-bensosyreester-hydroklorid, smp 216—218° fra aceton. 6-Methoxytropine benzoic acid ester hydrochloride, mp 216-218° from acetone.
6-metoksy-tropin-bensosyreester-hyd-robromid, smp 227—230° fra metanol/eter. 6-Methoxytropine benzoic acid ester hydrobromide, mp 227-230° from methanol/ether.
Eksempel 23: 6-metoksy-tropin-veratrumsyreester: En blanding av 5,5 g 6-metoksy-tropin og 13,5 g veratrumsyre-etylester blir varmet med ca. 0,2 g natriummetall i 30 timer i vakuum (5—10 mm Hg) til 125—130°. Til å begynne med er det en sterk blære- og skumdannelse på grunn av etanol som destillerer av, men denne opphører fullstendig mot sluttet av reaksjonstiden. Etter avkjølingen blir reaksjonsblandingen opptatt i 40 cm- > 2-n.saltsyre og ekstrahert med ialt 110 ems eter. Det vandige saltsure lag gjøres alkalisk under iskjøling med 25 pst. ammoniumhydroksydoppløsning, 6-metoksytropin-veratrumsyreester blir ekstrahert med til sammen 150 ems kloroform, de samlede kloroformekstrakter blir tørket over natriumsulfat og kloroformen dampet av i vakuum. Etter kort henstand krystalliserer resten, 6-metoksy-tropin-veratrumsyreester, C,sH2505N, gjennom. Smp 96—98° etter omkrystallisering fra bensol/ petroleter. Example 23: 6-methoxytropine-veratrum acid ester: A mixture of 5.5 g of 6-methoxy-tropine and 13.5 g of veratrum acid ethyl ester is heated with approx. 0.2 g of sodium metal for 30 hours in vacuum (5-10 mm Hg) at 125-130°. Initially, there is a strong bubble and foam formation due to ethanol distilling off, but this ceases completely towards the end of the reaction time. After cooling, the reaction mixture is taken up in 40 cm- > 2-n hydrochloric acid and extracted with a total of 110 ems of ether. The aqueous hydrochloric acid layer is made alkaline under ice-cooling with 25% ammonium hydroxide solution, 6-methoxytropin-veratrum acid ester is extracted with a total of 150 ems chloroform, the combined chloroform extracts are dried over sodium sulfate and the chloroform is evaporated off in vacuo. After a short stand, the residue, 6-methoxytropine-veratrum acid ester, C,sH2505N, crystallizes through. Mp 96-98° after recrystallization from benzol/petroleum ether.
Rensingen av esteren foregår best over 6-metoksy-tropinveratrum-syreester-hydrobromid, smp 209—211° fra metanol/ eter. The ester is best purified over 6-methoxytropine veratrum acid ester hydrobromide, mp 209-211° from methanol/ether.
6-metoksy-tropin-veratrumsyreester-hydroklorid, smp. 219—221° fra metanol/ eter. 6-Methoxytropin-veratrum ester hydrochloride, m.p. 219—221° from methanol/ether.
Eksempel 24: 6-metoksy-tropin-mandelsyreester Example 24: 6-Methoxytropine mandelic acid ester
(-metoksy-homatropin): (-methoxy-homatropin):
En blanding av 3,4 g 6-metoksy-tropin, 7,2 g mandelsyre-etylester og ca. 0,1 g natriummetall blir varmet i 30 timer i vakuum (ca. 5 mm Hg) til 125—130°. Etter avsluttet reaksjon blir reaksjonsblandingen opptatt i 40 cm». 2-n.saltsyre og rystet ut med ialt 100 cm:! eter. I tilskitning her-til blir det også ekstrahert med ialt .100 cm;i kloroform. Den sure vandige oppløs-ning blir deretter underlagt med 100 cm3 kloroform, gjort svakt alkalisk (svakt fenolftaleinalkalisk) under iskjøling med mettet sodaoppløsning og ekstrahert med ialt 400 cm3 kloroform. De samlede kloroformekstrakter blir tørket over natriumsulfat og kloroformen destillert av i vakuum. Saltene framstilles direkte av resten, 6-metoksy-tropin-mandelsyreester. A mixture of 3.4 g of 6-methoxytropine, 7.2 g of mandelic acid ethyl ester and approx. 0.1 g of sodium metal is heated for 30 hours in a vacuum (approx. 5 mm Hg) to 125-130°. After completion of the reaction, the reaction mixture is taken up in 40 cm". 2-n.hydrochloric acid and shaken out with a total of 100 cm:! ether. In addition to this, it is also extracted with a total of .100 cm; in chloroform. The acidic aqueous solution is then treated with 100 cm3 of chloroform, made weakly alkaline (weakly phenolphthalein alkaline) under ice-cooling with saturated soda solution and extracted with a total of 400 cm3 of chloroform. The combined chloroform extracts are dried over sodium sulphate and the chloroform is distilled off in vacuo. The salts are prepared directly from the residue, 6-methoxytropin-mandelic acid ester.
Av den svakt alkaliske vandige opp-løsning blir det ved blanding med konsen-trert natronlut, metning med koksalt og ekstrahering med kloroform gjenvunnet en liten mengde 6-metoksy-tropin (120 mg). Det sure eteriske uttrekk blir tørket over natriumsulfat, og eteren destillert av. Etter forsåping av . resten med natronlut og syring blir det dessuten gjenvunnet 1,8 g mandelsyre. A small amount of 6-methoxytropine (120 mg) is recovered from the weakly alkaline aqueous solution by mixing with concentrated caustic soda, saturating with common salt and extracting with chloroform. The acidic ethereal extract is dried over sodium sulfate, and the ether is distilled off. After saponification of . the remainder with caustic soda and acidification, 1.8 g of mandelic acid is also recovered.
Eksempel 25: Example 25:
6-etoksy-tropin-bensilsyreester: 6-ethoxy-tropine benzyl ester:
En blanding av 4,3 g 6-metoksy-tropin og 11,95 g bensilsyre-etylester blir varmet med ca. 0,2 g natriummetall i 30 timer i vakuum (ca. 1 mm Hg) til 125—130°. Mot slutten av reaksjonstiden kan det ikke len-ger konstateres noen blæredannelse. Etter avkjøling blir reaksjonsblandingen opptatt i 40 cm3 2-n. saltsyre og ekstrahert med 110 cm3 eter. Den vandige saltsure oppløsning blir derpå underlagt med 80 cm3 kloroform, iskjølet og gjort alkalisk med 25 pst. ammoniumhydroksydoppløs-ning. Derpå blir det rystet ut med ialt 400 cm3 kloroform, og de samlete kloroformekstrakter blir tørket over natriumsulfat. Etter avdestillering av kloroformen blir det tilbake en oljeaktig brun rest. Denne oppløses i litt etanol og filtreres gjennom benkull. Ved inndamping krystalliserer 6-etoksy-tropin-bensilsyreester, smp. 132— 134° ( fra etanol. 6-etoksy-tropin-bensilsyreester-hydroklorid smelter under spal-ting ved 100° etter omkrystallisering fra etanol/eter, 186—187° fra aceton. A mixture of 4.3 g of 6-methoxytropine and 11.95 g of benzylic acid ethyl ester is heated with approx. 0.2 g of sodium metal for 30 hours in vacuum (approx. 1 mm Hg) at 125-130°. Towards the end of the reaction time, no blistering can be observed anymore. After cooling, the reaction mixture is taken up in 40 cm3 2-n. hydrochloric acid and extracted with 110 cm3 of ether. The aqueous hydrochloric acid solution is then subjected to 80 cm 3 of chloroform, ice-cooled and made alkaline with 25% ammonium hydroxide solution. It is then shaken out with a total of 400 cm3 of chloroform, and the collected chloroform extracts are dried over sodium sulphate. After distilling off the chloroform, an oily brown residue remains. This is dissolved in a little ethanol and filtered through bone charcoal. On evaporation, 6-ethoxytropine benzylic acid ester crystallizes, m.p. 132—134° (from ethanol. 6-ethoxytropine benzyl ester hydrochloride melts with cleavage at 100° after recrystallization from ethanol/ether, 186—187° from acetone.
Eksempel 26: Example 26:
6-etoksy-tropin-bensosyreester: 6-ethoxy-tropine benzoic acid ester:
En blanding av 4,26 g etoksy-tropin og 6,9 g bensosyre-etylester blir oppvarmet med ca. 0,1 g natriummetall i 30 timer i vakuum (12 mm Hg) til 125—130°. Etter avkjøling blir reaksjonsblandingen opptatt i 40 cm3 2-n.saltsyre og ekstrahert med ialt 100 cm3 eter. Den vandige sure opp-løsning blir derpå underlagt med 50 cm3 kloroform, iskjølet og gjort svakt alkalisk (fenolftalein) med mettet sodaoppløsning. Man ekstraherer med til sammen 270 cm3 kloroform, tørket de samlete klorofoim-ekstrakter over natriumsulfat og destillerer av ekstraheringsmidlet i svakt vakuum. Den oljelignende rest (7,3 g) blir opptatt i 30 cm3 etanol og renset over benkull og aluminiumoksyd. A mixture of 4.26 g of ethoxytropine and 6.9 g of benzoic acid ethyl ester is heated with approx. 0.1 g of sodium metal for 30 hours in vacuum (12 mm Hg) at 125-130°. After cooling, the reaction mixture is taken up in 40 cm3 of 2-n hydrochloric acid and extracted with a total of 100 cm3 of ether. The aqueous acidic solution is then covered with 50 cm3 of chloroform, ice-cooled and made weakly alkaline (phenolphthalein) with saturated soda solution. Extraction is carried out with a total of 270 cm3 of chloroform, the collected chloroform extracts are dried over sodium sulphate and the extractant is distilled off in a weak vacuum. The oil-like residue (7.3 g) is taken up in 30 cm3 of ethanol and purified over bone charcoal and aluminum oxide.
6-etoksy-tropin-bensosyreester-hydro-bromid har smp. 192—194° etter omkrystallisering fra etanol/eter. 6-Ethoxy-tropine-benzoic acid ester-hydro-bromide has m.p. 192—194° after recrystallization from ethanol/ether.
Eksempel 27: N-butyl-6-metoksy-nortropin- bensilsyreester: 10 g n-butyl-6-metoksy-nortropin-hydroklorid blir hydret i 100 cm3 abs. metanol i autoklav med Raneynikkel i 5 timer ved 40—45° og et begynnelsestrykk på 60 at. Man filtrerer av fra katalysatoren og for damper løsningsmidlet i vakuum. Resten, n-butyl-6-metoksynortropin-hydroklorid Example 27: N-butyl-6-methoxy-nortropin- benzylic acid ester: 10 g of n-butyl-6-methoxy-nortropine hydrochloride are hydrated in 100 cm3 abs. methanol in an autoclave with Raney nickel for 5 hours at 40-45° and an initial pressure of 60 at. One filters off from the catalyst and for evaporate the solvent in vacuo. The remainder, n-butyl-6-methoxynortropine hydrochloride
krystalliserer fullstendig gjennom ved henstand ved romtemperatur. Ved omkrystallisering fra metanol/eter oppnås 2 former, som smelter ved 137—139° og 156—157°. crystallizes completely through on standing at room temperature. On recrystallization from methanol/ether, 2 forms are obtained, which melt at 137-139° and 156-157°.
N-butyl-6-metoksy-nortropin-hydro-bromid, smp. 120—122° (fra aceton). N-butyl-6-methoxy-nortropine hydrobromide, m.p. 120—122° (from acetone).
Den frie base oppnås ved å blande den vandige oppløsning av hydrokloridet med pottaske og ekstrahere med kloroform. N-butyl-6-metoksy-nortropin går over. som f arveløs olje i høyvakuum ved 0,4 mm Hg mellom 104 og 106°. The free base is obtained by mixing the aqueous solution of the hydrochloride with pot ash and extracting with chloroform. N-butyl-6-methoxy-nortropine wears off. as virgin oil in high vacuum at 0.4 mm Hg between 104 and 106°.
En blanding av 4,6 g n-butyl-6-metoksy-nortropin og 11 g bensilsyre-etylester blir oppvarmet med ca. 0,2 g natriummetall i 30 timer i vakuum (5—-10 mm Hg) til 125—130°. Reaksjonsblandingen blir derpå opptatt i 40 cm3 2-n.saltsyre og ekstrahert med ialt 110 cm3 eter. Den vandige saltsure oppløsning blir så underlagt med 50 ems kloroform, iskjølet, gjort alkalisk med 25 pst. ammoniumhydroksydoppløs-hihg og rystet ut med til sammen 300 cm3 kloroform. De samlede kloroformekstrakter blir tørket over natriumsulfat og kloroformen avdampet i svakt vakuum. Den mørkebrune oljeaktige rest blir opptatt i 20 ems metanol, varmet i kort tid med benkull og filtrert gjennom aluminiumoksyd og hyflo. Metanoloppløsningen av n-butyl-6-metoksy-nortropin-bensilsyre-esteren blir blandet med metanolisk saltsyre til en pH = 3 og fortettet til et lite volum. Ved tilsetning av litt eter krysalli-serer n-butyl-6-metoksy-nortropin-bensilsyreester-hydroklorid, smp. 221—222° fra metanol/eter. A mixture of 4.6 g of n-butyl-6-methoxy-nortropine and 11 g of benzylic acid ethyl ester is heated with approx. 0.2 g of sodium metal for 30 hours in vacuum (5—-10 mm Hg) at 125—130°. The reaction mixture is then taken up in 40 cm3 of 2-n hydrochloric acid and extracted with a total of 110 cm3 of ether. The aqueous hydrochloric acid solution is then treated with 50 ems of chloroform, ice-cooled, made alkaline with 25 percent ammonium hydroxide solution and shaken out with a total of 300 cm 3 of chloroform. The combined chloroform extracts are dried over sodium sulphate and the chloroform evaporated in a weak vacuum. The dark brown oily residue is taken up in 20 ems methanol, heated for a short time with bone charcoal and filtered through aluminum oxide and hyflo. The methanolic solution of the n-butyl-6-methoxy-nortropine benzylic acid ester is mixed with methanolic hydrochloric acid to a pH = 3 and concentrated to a small volume. On addition of a little ether, n-butyl-6-methoxy-nortropine benzyl ester hydrochloride, m.p. 221—222° from methanol/ether.
Eksempel 28: N-butyl-6-metoksy-nortropin-benso syreester: En blanding av 3,5 g n-butyl-6-metoksy-nortropin og 4,9 g bensosyre-etylester blir varmet med ca. 0,1 g natriummetall i 30 timer i vakuum (12 mm Hg) til 125—130°. Etter avkjøling blir reaksjonsblandingen opptatt i 40 cm3 2-n.saltsyre og ekstrahert med ialt 130 cm<3> eter. Den vandige saltsure oppløsning blir derpå underlagt med 50 ems kloroform, iskjølet og gjort alkalisk (fenolftalein) med 25 pst. ammoniumhydroksyd-oppløsning. Derpå ryster man ut med til sammen 270 cm3 kloroform, tørker de samlede kloroformekstrakter over natriumsulfat og damper kloroformen av i svakt vakuum. Den oljeaktige rest blir opptatt i 30 cm3 abs. metanol, og med metanolisk saltsyre blir n-butyl-6-meioksy-nortropin-bensosyreester-hydroklorid, smp. 221° frem-stillet fra metanol/eter. Example 28: N-butyl-6-methoxy-nortropine-benzo acid ester: A mixture of 3.5 g of n-butyl-6-methoxy-nortropine and 4.9 g of benzoic acid ethyl ester is heated with approx. 0.1 g of sodium metal for 30 hours in vacuum (12 mm Hg) at 125-130°. After cooling, the reaction mixture is taken up in 40 cm3 of 2-N hydrochloric acid and extracted with a total of 130 cm<3> of ether. The aqueous hydrochloric acid solution is then treated with 50 ems chloroform, ice-cooled and made alkaline (phenolphthalein) with 25% ammonium hydroxide solution. The mixture is then shaken out with a total of 270 cm3 of chloroform, the combined chloroform extracts are dried over sodium sulphate and the chloroform is evaporated off in a weak vacuum. The oily residue is taken up in 30 cm3 abs. methanol, and with methanolic hydrochloric acid becomes n-butyl-6-meoxy-nortropine-benzoic acid ester hydrochloride, m.p. 221° prepared from methanol/ether.
Eksempel 29: N-butyl-6-metoksy-nortropin- veratrumsyreester: En blanding av 4 g n-butyl-6-metoksy-nortropin og 7,8 g veratrumsyre-etylester blir varmet med ca. 0,1 g natriummetall i 30 timer i vakuum (ca. 1 mm Hg) til 125 —130°. Etter avkjøling blir reaksjonsblandingen opptatt i 50 cm» 2-n.saltsyre og ekstrahert med ialt 150 cm3 eter. Da hydro-kloridet er meget lett løselig i kloroform, blir det ekstrahert direkte fra den saltsure vandige oppløsning med ialt 300 cm3 kloroform. N-butyl-6-metoksy-nortropin-veratrumsyreester-hydroklorid, smp. 198° fra metanol/eter. Example 29: N-butyl-6-methoxy-nortropin- Veratrum acid ester: A mixture of 4 g of n-butyl-6-methoxy-nortropine and 7.8 g of veratrum acid ethyl ester is heated with approx. 0.1 g of sodium metal for 30 hours in vacuum (about 1 mm Hg) at 125 —130°. After cooling, the reaction mixture is taken up in 50 cm3 of 2-n hydrochloric acid and extracted with a total of 150 cm3 of ether. As the hydrochloride is very easily soluble in chloroform, it is extracted directly from the hydrochloric acid aqueous solution with a total of 300 cm3 of chloroform. N-butyl-6-methoxy-nortropine veratrum ester hydrochloride, m.p. 198° from methanol/ether.
Eksempel 30: Example 30:
N-butyl-6-etoksy-nortropin-bensil- N-butyl-6-ethoxy-nortropine-benzyl-
v syreester: v acid esters:
10 g n-butyl-6-etoksy-nortropinon blir hydrert i 100 cm3 abs metanol i autoklav med Raneynikkel i 5 timer ved 40—45° og 60 at. Etter avfiltrering fra katalysatoren 10 g of n-butyl-6-ethoxy-nortropinone is hydrated in 100 cm3 abs methanol in an autoclave with Raney nickel for 5 hours at 40-45° and 60 at. After filtration from the catalyst
og avdestillering av løsningsmidlet blir resten destillert i høyvakuum. Kp. 100— 108° ved 0,005 mm Hg. and distilling off the solvent, the residue is distilled in high vacuum. Kp. 100— 108° at 0.005 mm Hg.
En blanding av 8 g n-butyl-6-etoksy-nortropin og 18 g bensilsyreester blir varmet med ca. 0,1 g natriummetall i 30 timer i vakuum (ca. 1 mm Hg) til 125—130°" Etter avkjøling blir reaksjonsblandingen Opptatt i 50 cm- 2-n-saltsyré og ekstrahert med ialt 110 cm- eter. Den vandige oppløsning blir derpå underlagt med 50 cm'-- kloroform, kjølet med is, gjort alkalisk med 25 pst. ammonium-hydroksydoppløsning, og ekstrahert med ialt 280 ems kloroform. De samlede klorb-formekstrakter blir tørket over natriumsulfat, ekstraheringsmidlet avdampet i vakuum og den oljeaktige, brune rest renset over benkull og aluminiumoksyd. A mixture of 8 g of n-butyl-6-ethoxy-nortropine and 18 g of benzylic acid ester is heated with approx. 0.1 g of sodium metal for 30 hours in vacuum (approx. 1 mm Hg) to 125—130°" After cooling, the reaction mixture is taken up in 50 cm-2-n-hydrochloric acid and extracted with a total of 110 cm- ether. The aqueous solution is then covered with 50 cm'-- chloroform, cooled with ice, made alkaline with 25 percent ammonium hydroxide solution, and extracted with a total of 280 ems chloroform. The combined chloroform extracts are dried over sodium sulfate, the extractant evaporated in vacuo and the oily, brown residue purified over bone charcoal and aluminum oxide.
N-butyl-6-etoksy-nortropin-bensilsyreester-hydroklorid, smp. 212—215° fra etanol/eter eller fra aceton/eter. N-butyl-6-ethoxy-nortropine benzyl ester hydrochloride, m.p. 212—215° from ethanol/ether or from acetone/ether.
Eksempel 31: N-butyl-6-etoksy-nortropin- bensosyreester: En blanding av 5 g n-butyl-6-etoksy-nortropin og 6,6 g bensosyre-etylester blir varmet med ca. 0,2 g natriummetall i 30 timer i vakuum (ca. 1 mm Hg) til 125—• 130°. Etter avkjøling blir reaksjonsblandingen opptatt i 50 ems 2-n.saltsyre og ekstrahert med ialt 110 cm*! eter. Den saltsure vandige oppløsning blir derpå underlagt med ca. 50 ems kloroform, kjølet med is, og gjort alkalisk med 25 pst. ammonium-hydroksydoppløsning og ekstrahert med ialt 300 cm3 kloroform. De samlede kioro-formekstrakter blir tørket over natriumsulfat, ekstraheringsmidlet avdampet i vakuum og den oljeaktige, brune rest renset over benkull og aluminiumoksyd. Example 31: N-butyl-6-ethoxy-nortropin- Benzoic acid ester: A mixture of 5 g of n-butyl-6-ethoxy-nortropine and 6.6 g of benzoic acid ethyl ester is heated with approx. 0.2 g of sodium metal for 30 hours in vacuum (about 1 mm Hg) at 125—• 130°. After cooling, the reaction mixture is taken up in 50 ems of 2-n hydrochloric acid and extracted with a total of 110 cm*! ether. The hydrochloric acid aqueous solution is then treated with approx. 50 ems chloroform, cooled with ice, and made alkaline with 25 per cent ammonium hydroxide solution and extracted with a total of 300 cm3 chloroform. The combined chioroform extracts are dried over sodium sulphate, the extractant evaporated in vacuo and the oily, brown residue purified over bone charcoal and aluminum oxide.
N-bytyl-6-etoksy-nortropin-bensosyreester-hydroklorid, smp. 195—197° fra etanol/eter. N-butyl-6-ethoxy-nortropine benzoic acid ester hydrochloride, m.p. 195—197° from ethanol/ether.
Eksempel 32: 6-isopropoksy-tropin-bensilsyreester- hydroklorid: 5 g 6-isopropoksy-tropinon-hydroklorid blir hydrert i 50 cm°> abs etanol i autoklav med Raneynikkel i 5 timer ved 40° og et begynnelsestrykk på 60 at. Man filtrerer av fra katalysatoren og fordamper løs-ningsmidlet i vakuum, opptar resten i vann og ekstraherer den vandige oppløs-ning som er mettet med kalium-karbonat flere ganger med kloroform. Kloroform-oppløsningen som er tørket over natriumsulfat etterlater ved inndamping i vakuum 6-isopropoksy-tropin som destillerer som farveløs olje ved 0,75 mm Hg ved 122—126°. Example 32: 6-Isopropoxytropine Benzyl Ester hydrochloride: 5 g of 6-isopropoxy-tropinone hydrochloride is hydrated in 50 cm°> abs ethanol in an autoclave with Raney nickel for 5 hours at 40° and an initial pressure of 60 at. The catalyst is filtered off and the solvent is evaporated in vacuo, the residue is taken up in water and the aqueous solution, which is saturated with potassium carbonate, is extracted several times with chloroform. The chloroform solution dried over sodium sulfate leaves on evaporation in vacuo 6-isopropoxytropine which distils as a colorless oil at 0.75 mm Hg at 122-126°.
En blanding av 2,6 g 6-isopropoksy-tropin og 6,7 g bensilsyre-etylester blir varmet med ca. 0,1 g natriummetall i 30 timer i vakuum (ca. 1 mm Hg) til 125—130°'. Etter avsluttet reaksjon blir den avkjølte reaksjonsblanding opptatt i 40 cm3 2-n. saltsyre og ekstrahert med ialt 80 cm?> eter. Det vandige saltsure lag blir underlagt med" 50 cm3 kloroform, blandet under iskjøling med 25 pst. ammoniumhydroksydoppløs-ning inntil alkalisk reaksjon og ekstrahert med ialt 250 cm3 kloroform. De samlede kloroformuttrekk som er tørket over natriumsulfat etterlater ved inndamping en oljeaktig, brun rest som opptas i litt etanol og filtreres gjennom benkull og aluminiumoksyd. Etter avdamping av metanolen i vakuum blir det tilbake som oljeaktig, brun rest 6-isopropoksy-tropin-bensilsyreester, hvis hydroklorid etter omkrystallisering fra metanol/eter har et smp. på 116—118°. A mixture of 2.6 g of 6-isopropoxytropine and 6.7 g of benzylic acid ethyl ester is heated with approx. 0.1 g of sodium metal for 30 hours in vacuum (about 1 mm Hg) at 125-130°'. After completion of the reaction, the cooled reaction mixture is taken up in 40 cm3 2-n. hydrochloric acid and extracted with a total of 80 cm?> of ether. The aqueous hydrochloric acid layer is treated with 50 cm3 of chloroform, mixed under ice-cooling with a 25% ammonium hydroxide solution until an alkaline reaction and extracted with a total of 250 cm3 of chloroform. The combined chloroform extracts, which are dried over sodium sulfate, leave an oily, brown residue on evaporation which taken up in a little ethanol and filtered through bone charcoal and aluminum oxide. After evaporation of the methanol in a vacuum, it remains as an oily, brown residue 6-isopropoxytropine benzylic acid ester, the hydrochloride of which after recrystallization from methanol/ether has a melting point of 116-118° .
Eksempel 33: 6-metoksy-pseudo-tropin-bensosyre ester-hy dr oklorid: En blanding av 5,9 g 6-metoksy-pseudo-<;>tropin og 10,3 g bensosyreetylester blir opp-.varmet med ca. 0,2 g natrium i 30 timer i vakuum (opptil 1 mm Hg) til 125—130°. Example 33: 6-Methoxy-pseudo-tropine-benzoic acid ester hydrochloride: A mixture of 5.9 g of 6-methoxy-pseudo-<;>tropine and 10.3 g of benzoic acid ethyl ester is heated with approx. 0.2 g of sodium for 30 hours in vacuum (up to 1 mm Hg) at 125-130°.
(Etter avsluttet reaksjon blir den avkjølte jreaksjonsblanding opptatt i 50 cm3 2-n. ^saltsyre og rystet ut med ialt 240 cm3 eter. ;Den vandige saltsure oppløsning ekstraheres med ialt 300 cm3 kloroform, de samlede kloroformuttrekk tørkes over natrium--sulfat, og løsningsmidlet fordampes i vakuum. Resten, 6-metoksy-pseudo-tropin-sbensosyreester-hydroklorid blir opptatt i 'metanol, filtrert gjennom benkull' og omkrystallisert fra metanol/eter. Smp. 256— |259°. (After completion of the reaction, the cooled reaction mixture is taken up in 50 cm3 of 2-n hydrochloric acid and shaken out with a total of 240 cm3 of ether. The aqueous hydrochloric acid solution is extracted with a total of 300 cm3 of chloroform, the combined chloroform extracts are dried over sodium sulfate, and the solvent is evaporated in vacuo. The residue, 6-methoxy-pseudo-tropine-benzoic acid ester hydrochloride, is taken up in 'methanol, filtered through bone charcoal' and recrystallized from methanol/ether, mp 256— |259°.
Eksempel 34: 6-metoksy-pseudo-tropin-veratrumsyreester-hydroklorid: En blanding av 5,4 g 6-metoksy-pseudo-! tropin og 13,3 g veratrumsyre-etylester blir I oppvarmet med ca. 0,2 g natrium i 30 timer ;i vakuum (opptil 1 mm Hg) til 130°. Etter i avsluttet reaksjon blir den avkjølte reaksjonsblanding opptatt i 50 cm3 2-n.saltsyre jog rystet ut med ialt 240 cm3 eter. Example 34: 6-Methoxy-pseudo-tropine-veratrum ester hydrochloride: A mixture of 5.4 g of 6-methoxy-pseudo-! tropine and 13.3 g of veratric acid ethyl ester are heated with approx. 0.2 g of sodium for 30 hours; in vacuum (up to 1 mm Hg) at 130°. After the reaction has ended, the cooled reaction mixture is taken up in 50 cm3 of 2-n hydrochloric acid and shaken out with a total of 240 cm3 of ether.
Den vandige saltsure oppløsning blir [ekstrahert med ialt 300 cm3 kloroform, de samlede kloroformuttrekk blir tørket over I natriumsulfat og løsningsmidlet fordampet i i vakuum. Resten, 6-metoksy-pseudo-tropin- veratrumsyreester-hydroklorid, blir :opptatt i metanol, filtrert gjennom benkull og omkrystallisert fra metanol/eter. Smp. 228—229°. The aqueous hydrochloric acid solution is extracted with a total of 300 cm 3 of chloroform, the combined chloroform extracts are dried over sodium sulfate and the solvent is evaporated in vacuo. The residue, 6-methoxy-pseudo-tropine-veratrum acid ester hydrochloride, is taken up in methanol, filtered through bone charcoal and recrystallized from methanol/ether. Temp. 228—229°.
Eksempel 35: N-butyl-6-metoksy-pseudo-nortropin-bensosyreester-hydroklorid: Til en kokende oppløsning av 15 g n-butyi-6-metoksy-hortropinon i 150 cm» abs etanol blir det under omrøring i løpet av 2 timer porsjonsvis tilsatt 16 g natrium. Reaksjonsblandingen destilleres med vanndamp, resten ekstraheres med ialt 500 cm3 eter, eteren dampes av etter tørking over natriumsulfat, og resten fraksjoneres i høy-vakuum. N-butyl-6-metoksy-pseudo-nor-tropin koker ved 112—114° ved 0,25 mm Hg. Example 35: N-butyl-6-methoxy-pseudo-nortropine-benzoic acid ester hydrochloride: To a boiling solution of 15 g of n-butyl-6-methoxy-hortropinone in 150 cm» abs ethanol is added with stirring during 2 hours portionwise added 16 g of sodium. The reaction mixture is distilled with steam, the residue is extracted with a total of 500 cm3 of ether, the ether is evaporated off after drying over sodium sulphate, and the residue is fractionated in high vacuum. N-butyl-6-methoxy-pseudo-nor-tropine boils at 112—114° at 0.25 mm Hg.
En blanding av 1,7 g n-butyl-metoksy-pseudo-nortropin og 2,43 g bensosyre-etylester blir varmet med ca. 0,2 g natrium i 30 timer under tilbakeløp i vakuum (opptil 1 mm Hg) til 125—130°. Etter avsluttet reaksjon blir den avkjølte reaksjonsblanding opptatt i 60 cm3 2-n.saltsyre og rystet ut med ialt 260 cm3 eter. Den vandige saltsure oppløsning blir ekstrahert med ialt 400 cm3 kloroform, de samlede kloroformuttrekk blir tørket over natriumsulfat, og løsningsmidlet fordampet i vakuum. Resten, n-butyl-6-metoksy-pseudo-nortropin-bensosyreester-hydroklorid, blir opptatt i metanol, filtrert gjennom benkull og brakt til å krystallisere fra metanol/eter. Smp. 259—261°. A mixture of 1.7 g of n-butyl-methoxy-pseudo-nortropine and 2.43 g of benzoic acid ethyl ester is heated with approx. 0.2 g sodium for 30 hours under reflux in vacuum (up to 1 mm Hg) to 125-130°. After completion of the reaction, the cooled reaction mixture is taken up in 60 cm3 of 2-n hydrochloric acid and shaken out with a total of 260 cm3 of ether. The aqueous hydrochloric acid solution is extracted with a total of 400 cm 3 of chloroform, the combined chloroform extracts are dried over sodium sulfate, and the solvent is evaporated in vacuo. The residue, n-butyl-6-methoxy-pseudo-nortropine-benzoic acid ester hydrochloride, is taken up in methanol, filtered through charcoal and allowed to crystallize from methanol/ether. Temp. 259—261°.
Eksempel 36: N-butyl-6-metoksy-pseudo-nortropin- veratrumsyreester-hy droklorid : En blanding av 3,4 g n-butyl-6-metoksy-pseudo-nortropin og 6,8 g veratrumsyre-etylester blir varmet med ca. 0,2 g natrium i 30 timer i vakuum (opptil 1 mm Hg) til 125—130°. Etter avsluttet reaksjon blir den avkjølte reaksjonsblanding opptatt i 50 cm3 2-n.saltsyre og rystet ut med ialt 230 cm3 eter. Den vandige saltsure oppløsning blir ekstrahert med ialt 300 cm3 kloroform, de samlede kloroformuttrekk tørket over natriumsulfat, og løsningsmidlet fordampet i vakuum. Resten, n-butyl-6-metoksy-pseudo-nortropin-veratrumsyreester-hydroklorid blir opptatt i metanol, filtrert gjennom benkull og omkrystallisert fra metanol/eter. Nåler med smp. 198—200°. Example 36: N-butyl-6-methoxy-pseudo-nortropin- Veratric acid ester hydrochloride: A mixture of 3.4 g of n-butyl-6-methoxy-pseudo-nortropine and 6.8 g of veratric acid ethyl ester is heated with approx. 0.2 g of sodium for 30 hours in vacuum (up to 1 mm Hg) at 125-130°. After completion of the reaction, the cooled reaction mixture is taken up in 50 cm3 of 2-n hydrochloric acid and shaken out with a total of 230 cm3 of ether. The aqueous hydrochloric acid solution is extracted with a total of 300 cm3 of chloroform, the combined chloroform extracts dried over sodium sulfate, and the solvent evaporated in vacuo. The residue, n-butyl-6-methoxy-pseudo-nortropine-veratrum ester hydrochloride, is taken up in methanol, filtered through bone charcoal and recrystallized from methanol/ether. Needles with m.p. 198—200°.
Eksempel 37: 6-metoksy-tropin-ftalsyre-etylester- hydroklorid: En blanding av 4 g 6-metoksy-tropin og 5,59 g ftalsyre-etylester blir varmet med ca. 0,2 g natrium i 30 timer i vakuum (opptil 1 mm Hg) til 125—130°. Etter avsluttet reaksjon blir den avkjølte reaksjonsblanding opptatt i 40 cm3 2-n.saltsyre og rystet ut med ialt 100 cm3 eter. Den vandige saltsure oppløsning ekstraheres med ialt 300 ems kloroform, de samlede kloroformut trekk tørkes over natriumsulfat, og løs-ningsmidlet fordampes i vakuum. Den oljeaktige rest blir opptatt i metanol, filtrert gjennom benkull og brakt til å krystallisere fra metanol/eter. 6-metoksy-tropin-ftalsyre-etylester-hydroklorid smelter ved 168—169°. Example 37: 6-methoxy-tropine-phthalic acid-ethyl ester- hydrochloride: A mixture of 4 g of 6-methoxytropine and 5.59 g of phthalic acid ethyl ester is heated with approx. 0.2 g of sodium for 30 hours in vacuum (up to 1 mm Hg) at 125-130°. After completion of the reaction, the cooled reaction mixture is taken up in 40 cm3 of 2-n hydrochloric acid and shaken out with a total of 100 cm3 of ether. The aqueous hydrochloric acid solution is extracted with a total of 300 ems chloroform, the combined chloroform out extract is dried over sodium sulfate, and the solvent is evaporated in vacuo. The oily residue is taken up in methanol, filtered through bone charcoal and brought to crystallize from methanol/ether. 6-Methoxy-tropine-phthalic acid-ethyl ester-hydrochloride melts at 168-169°.
Eksempel 38: 6-etoksy-pseudo-tropin-bensilsyreester- hydroklorid: En blanding av 5,1 g 6-etoksy-pseudo-tropin og 14,1 g bensilsyre-etylester blir varmet med ca. 0,2 g natrium i 30 timer i vakuum (opptil 1 mm Hg) til 110—115°. Etter avsluttet reaksjon blir den avkjølte reaksjonsblanding opptatt i 50 cm3 2-n. saltsyre og rystet ut med ialt 260 cm» eter. Den vandige saltsure oppløsning blir-ekstrahert med ialt 260 cm3 kloroform, de samlede kloroformuttrekk tørket over natriumsulfat, og løsningsmidlet fordampet i vakuum. Resten, 6-etoksy-pseudo-trbpin-bensilsyreester-hydroklorid, blir opptatt i etanol, filtrert gjennom benkull, fortettet og brakt til å krystallisere ved å blandes med eter. Smp. 219—221° (sp.). Eksempel 39: N-bensyl-6-etoksy-nortropin-bensil syreester: 28,4 g n-bensyl-6-etoksy-nortropinon blir hydrert i 250 cm3 abs etanol i autoklav med Raney-nikkel i 5 timer ved 40—45° og et begynnelsestrykk på 60 at. Man filtrerer av fra katalysatoren, damper alkoholen av i svakt vakuum og destillerer resten i høyvakuum. Kp. 128° ved 0,06 mm Hg. Example 38: 6-ethoxy-pseudo-tropine-benzylic acid ester- hydrochloride: A mixture of 5.1 g of 6-ethoxy-pseudo-tropine and 14.1 g of benzylic acid ethyl ester is heated with approx. 0.2 g of sodium for 30 hours in vacuum (up to 1 mm Hg) at 110—115°. After completion of the reaction, the cooled reaction mixture is taken up in 50 cm3 2-n. hydrochloric acid and shaken out with a total of 260 cm» of ether. The aqueous hydrochloric acid solution is extracted with a total of 260 cm 3 of chloroform, the combined chloroform extracts are dried over sodium sulfate, and the solvent is evaporated in vacuo. The residue, 6-ethoxy-pseudo-trbpine-benzyl ester hydrochloride, is taken up in ethanol, filtered through charcoal, concentrated and brought to crystallize by mixing with ether. Temp. 219—221° (sp.). Example 39: N-benzyl-6-ethoxy-nortropin-benzyl acid ester: 28.4 g of n-benzyl-6-ethoxy-nortropinone is hydrated in 250 cm3 abs ethanol in an autoclave with Raney nickel for 5 hours at 40-45° and an initial pressure of 60 at. One filters off the catalyst, evaporates the alcohol in a weak vacuum and distills the remainder in a high vacuum. Kp. 128° at 0.06 mm Hg.
En blanding av 6 g n-bensyl-6-etoksy-nortropin og 11,8 g bensilsyre-etylester blir varmet med ca. 0,2 g natriummetall i 30 timer i vakuum (ca. 1 mm Hg) med tilbake-løp til 125—130°. Reaksjonsblandingen. blir etter avkjøling opptatt i 50 ems 2-n.saltsyre og ekstrahert med ialt 130 cm3 eter. Den vandige saltsure lag blir rystet ut "med ialt 300 ems kloroform, kloroformekstrakten tørket over natriumsulfat og dampet inn i vakuum. Resten løses i litt etanol, filtreres gjennom benkull, og hydrokloridet bringes til å krystallisere fra etanol/eter. N-bensyl-6-etoksy-nortropin-bensilsyreester-hydroklorid krystalliserer fra etanol i kvaster av samlede nåler med smp. 211— 212°. A mixture of 6 g of n-benzyl-6-ethoxy-nortropine and 11.8 g of benzylic acid ethyl ester is heated with approx. 0.2 g of sodium metal for 30 hours in vacuum (approx. 1 mm Hg) with reflux to 125-130°. The reaction mixture. is, after cooling, taken up in 50 ems of 2-n hydrochloric acid and extracted with a total of 130 cm3 of ether. The aqueous hydrochloric acid layer is shaken out with a total of 300 ems of chloroform, the chloroform extract is dried over sodium sulfate and evaporated in vacuo. The residue is dissolved in a little ethanol, filtered through charcoal, and the hydrochloride is crystallized from ethanol/ether. N-benzyl-6 -Ethoxy-nortropine-benzyl ester hydrochloride crystallizes from ethanol in tufts of aggregated needles, mp 211— 212°.
Eksempel 40: N-bensyl-6-metoksy-nortropin-bensil syreester-hydroklorid: 5 g n-bensyl-6-metoksy-nortropinon blir hydrert i 50 cm3 abs metanol i autoklav med Raney-nikkel i 5 timer ved 40—.45° og et begynnelsestrykk på 60 at. Man filtrerer av fra katalysatoren og fordamper løsnings-midlet i vakuum. Resten blir fraksjonert i høyvakuum. N-bensyl-6-metoksy-nortro-pin-pikrat smelter etter omkrystallisering fra etanol eller aceton ved 190—192° (sp.). En blanding av 12 g n-bensyl-6-metoksy-nortropin og 24,8 g bensilsyre-etylester blir varmet med ca. 0,3 g natriummetall i 30 timer i vakuum (ca. 1 mm Hg) med tilbakeløp til 120—130°. Reaksjonsblandingen blir etter avkjøling opptatt i 60 cm3 2-n.saltsyre og ekstrahert med ialt 330 cm3 eter. Det vandige saltsure lag blir rystet ut med ialt 390 cm» kloroform, kloroformekstrakten tørket og inndampet i vakuum. Resten løses i litt metanol, kokes opp kortvarig med benkull og filtreres gjennom hyflo. Fra den fortettede oppløs-ning blir det etter blanding med eter kry-stallisert ut n-bensyl-6-metoksy-nortropin-berisylsyreester-hydroklorid med smp. 238 —240°. Example 40: N-benzyl-6-methoxy-nortropin-benzyl acid ester hydrochloride: 5 g n-benzyl-6-methoxy-nortropinone is hydrated in 50 cm3 abs methanol in an autoclave with Raney nickel for 5 hours at 40-.45° and an initial pressure of 60 at. The catalyst is filtered off and the solvent is evaporated in a vacuum. The rest is fractionated in high vacuum. N-benzyl-6-methoxy-nortropine picrate melts after recrystallization from ethanol or acetone at 190-192° (m.p.). A mixture of 12 g of n-benzyl-6-methoxy-nortropine and 24.8 g of benzylic acid ethyl ester is heated with approx. 0.3 g of sodium metal for 30 hours in vacuum (approx. 1 mm Hg) with reflux to 120-130°. After cooling, the reaction mixture is taken up in 60 cm3 of 2-n hydrochloric acid and extracted with a total of 330 cm3 of ether. The aqueous hydrochloric acid layer is shaken out with a total of 390 cm" of chloroform, the chloroform extract dried and evaporated in vacuo. The residue is dissolved in a little methanol, boiled briefly with bone charcoal and filtered through hyflo. After mixing with ether, n-benzyl-6-methoxy-nortropine berisylic acid ester hydrochloride with m.p. is crystallized from the concentrated solution. 238 -240°.
Eksempel 41: N-bensyl-6-metoksy-nortropin-benso syreester-hydroklorid: En blanding av 8 g n-bensyl-6-metoksy-nortropin og 10,3 g bensosyre-etylester blir Example 41: N-benzyl-6-methoxy-nortropine-benzo acid ester hydrochloride: A mixture of 8 g of n-benzyl-6-methoxy-nortropine and 10.3 g of benzoic acid ethyl ester becomes
varmet med ca. 0,2 g natriummetall i 30 heated with approx. 0.2 g of sodium metal in 30
timer i vakuum (ca. 1 mm Hg) med tilbake-løp til 120—130°. Reaksjonsblandingen opptas etter avkjøling i 50 ems 2-n.saltsyre hours in vacuum (approx. 1 mm Hg) with reflux to 120-130°. The reaction mixture is taken up after cooling in 50 ems 2-n hydrochloric acid
og ekstraheres med ialt 170 ems eter. Det and extracted with a total of 170 ems of ether. The
vandige saltsure lag blir rystet ut med ialt aqueous hydrochloric acid layers are shaken out with ialt
340 ems kloroform, kloroformekstrakten 340 ems chloroform, the chloroform extract
tørket og inndampet i vakuum. Resten lø-ses i litt metanol, kokes kortvarig opp med dried and evaporated in vacuo. The remainder is dissolved in a little methanol, briefly boiled with
benkull og filtreres gjennom hyflo. Fra den bone charcoal and filtered through hyflo. From it
fortettede oppløsning krystalliseres det ut condensed solution it crystallizes out
etter blanding med eter n-bensyl-6- after mixing with ether n-benzyl-6-
metoksy-nortropin-bensosyreester-hydroklorid med smp. 200—202°. Methoxy-nortropine-benzoic acid ester hydrochloride with m.p. 200-202°.
Eksempel 42: N-bensyl-6-metoksy-norpseudotropin- bensosyreester-hydroklorid: Til en kokende oppløsning av 15 g n-bensyl-6-metoksy-nortropinon i 170 ems abs etanol blir det under røring porsjonsvis i løpet av 2 timer satt 15 g natrium. Reaksjonsblandingen destilleres med vanndamp, resten ekstraheres med ialt 300 ems eter, eteren dampes av etter tørking over natriumsulfat, og resten fraksjoneres i høy-vakuum. N-bensyl-6-metoksy-norpseudo-tropin koker ved 149—151° ved 0,06 mm Hg. Example 42: N-benzyl-6-methoxy-norpseudotropin- Benzoic acid ester hydrochloride: To a boiling solution of 15 g of n-benzyl-6-methoxy-nortropinone in 170 ems abs ethanol, 15 g of sodium are added portionwise over the course of 2 hours while stirring. The reaction mixture is distilled with steam, the residue is extracted with a total of 300 ems of ether, the ether is evaporated off after drying over sodium sulphate, and the residue is fractionated in high vacuum. N-benzyl-6-methoxy-norpseudo-tropine boils at 149-151° at 0.06 mm Hg.
En blanding av 5 g n-bensyl-6-metoksy-norpseudotropin og 6,4 g bensosyre-etylester blir varmet med ca. 0,2 g natriummetall i 30 timer i vakuum (ca. 1 mm Hg) med tilbakeløp til 120—130°. Reaksjonsblandingen blir etter avkjøling opptatt i 60 ems 2-n.saltsyre og ekstrahert med ialt A mixture of 5 g of n-benzyl-6-methoxy-norpseudotropin and 6.4 g of benzoic acid ethyl ester is heated with approx. 0.2 g of sodium metal for 30 hours in vacuum (approx. 1 mm Hg) with reflux to 120-130°. After cooling, the reaction mixture is taken up in 60 ems of 2-n hydrochloric acid and extracted with total
230 cm:t eter. Det vandige saltsure lag blir rystet ut med ialt 300 ems kloroform, kloroformekstrakten tørket og inndampet i vakuum. Resten løses i litt metanol, kokes kortvarig opp med benkull og filtreres gjennom hyflo. Fra den fortettede oppløs-ning krystalliseres det ut etter blanding med eter n-bensyl-6-metoksy-norpseudo-tropin-bensosyreester-hydroklorid med 230 cm:t ether. The aqueous hydrochloric acid layer is shaken out with a total of 300 ems chloroform, the chloroform extract dried and evaporated in vacuo. The residue is dissolved in a little methanol, briefly boiled with bone charcoal and filtered through hyflo. From the concentrated solution, it crystallizes out after mixing with ether n-benzyl-6-methoxy-norpseudo-tropine-benzoic acid ester hydrochloride with
smp. 250—252°. m.p. 250-252°.
Claims (1)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CH1000965A CH441190A (en) | 1965-07-16 | 1965-07-16 | Process for improving the lighting conditions in rooms with incidence of daylight and equipment for carrying out this process |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| NO116055B true NO116055B (en) | 1969-01-20 |
Family
ID=4358381
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO16395066A NO116055B (en) | 1965-07-16 | 1966-07-15 |
Country Status (6)
| Country | Link |
|---|---|
| BE (1) | BE684164A (en) |
| CH (1) | CH441190A (en) |
| DE (1) | DE1497348A1 (en) |
| GB (1) | GB1148677A (en) |
| NL (1) | NL6609988A (en) |
| NO (1) | NO116055B (en) |
Families Citing this family (27)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE2807421A1 (en) * | 1978-02-22 | 1979-08-23 | Eltreva Ag | DEVICE FOR AIR CONDITIONING A CLOSED ROOM |
| EP0020296B1 (en) * | 1979-06-05 | 1983-06-01 | Relium AG | Method and means for controlling the radiation energy of the total spectrum in rooms |
| JPS56119365A (en) * | 1980-02-26 | 1981-09-18 | Honda Motor Co Ltd | Composite working device of boring and honing |
| GB2141474B (en) * | 1983-06-17 | 1987-03-04 | British Res Agricult Eng | Louvred reflector |
| JPS6012506A (en) * | 1983-07-01 | 1985-01-22 | Takashi Mori | Optical radiator |
| EP0200876B1 (en) * | 1985-04-30 | 1988-11-02 | Siemens Aktiengesellschaft | Arrangement for lighting a room with daylight |
| DE3517610A1 (en) * | 1985-05-15 | 1986-11-20 | GGN Glashandels-Gesellschaft Nördlingen mbH & Co KG, 8860 Nördlingen | MULTIPLE DISC INSULATING GLASS UNIT WITH INTEGRATED LIGHT-GUIDING SYSTEM |
| US4820020A (en) * | 1987-11-19 | 1989-04-11 | Terrill Frank E | Passive daylighting system |
| AU643429B2 (en) * | 1989-02-28 | 1993-11-18 | Helmut Koster | Light deflecting system for lighting an indoor area |
| GB2231080A (en) * | 1989-03-03 | 1990-11-07 | John Barrie Timmons | Thermally efficient roof |
| DE4211085A1 (en) * | 1992-04-03 | 1993-10-07 | Koester Helmut | Double glazed window with internal reflectors - has slats arranged to deflect sun's rays to provide more effective illumination in room |
| DE4302883A1 (en) * | 1992-10-06 | 1994-04-07 | Colt Int Holdings | Shading device for facade or roof elements provided with glazing |
| DE4310717A1 (en) * | 1993-04-01 | 1994-10-06 | Koester Helmut | Light-guiding elements for daylight |
| DE29506194U1 (en) * | 1995-04-10 | 1995-06-08 | Wolters, Paolo, 12555 Berlin | Window element for shielding and illuminating interiors |
| DE19632684A1 (en) * | 1996-08-14 | 1998-02-19 | Idl Ind Und Licht Design Gmbh | Lamella louvre blind |
| DE19708778B4 (en) * | 1997-03-04 | 2007-08-30 | Dozsa-Farkas Jun., Andras | lighting system |
| GB9710034D0 (en) * | 1997-05-16 | 1997-07-09 | Secretary Trade Ind Brit | Roller blind or curtain |
| DE29813771U1 (en) * | 1998-08-01 | 1999-12-16 | Hüppe Form Sonnenschutzsysteme GmbH, 26133 Oldenburg | Slat arrangement for sun protection devices |
| DE20112740U1 (en) * | 2001-08-08 | 2002-07-11 | Funken, Stefan, 47506 Neukirchen-Vluyn | Louver curtain for windows |
| DE10161159A1 (en) * | 2001-08-10 | 2003-07-03 | Ulrich Clauss | sheet |
| DE10161938A1 (en) | 2001-12-17 | 2003-06-18 | Fraunhofer Ges Forschung | Sun-light protection device for buildings, uses structured elements each provided with triangular cross-sectional surface |
| FR2847615B1 (en) * | 2002-11-27 | 2005-08-05 | Philippe Bessard | STORE WITH ORIENTABLE BLADES |
| DE102005032657A1 (en) * | 2005-07-13 | 2007-02-01 | Hydro Building Systems Gmbh | Sunshade for buildings has sheet to modify sunlight passing into building and lights to provide artificial light directly or indirectly to the building |
| NL1033785C1 (en) * | 2007-05-01 | 2008-11-04 | Roeland Jan Spanjaard | Blinds with lighting. |
| DE102009056362B4 (en) * | 2009-11-30 | 2012-10-04 | Helmut Köster | Light-deflecting blind with prismatically shaped louvre surfaces for the deflection and deflection of sunlight |
| DE202012005524U1 (en) * | 2012-04-12 | 2013-07-15 | Bartenbach Holding Gmbh | Device for illuminating rooms with daylight and / or artificial light |
| WO2019204255A1 (en) * | 2018-04-19 | 2019-10-24 | AGrow-Ray Technologies, Inc. | Shade and shadow minimizing extrusion luminaire |
-
1965
- 1965-07-16 CH CH1000965A patent/CH441190A/en unknown
-
1966
- 1966-07-11 DE DE19661497348 patent/DE1497348A1/en active Pending
- 1966-07-14 BE BE684164D patent/BE684164A/xx unknown
- 1966-07-15 GB GB3186366A patent/GB1148677A/en not_active Expired
- 1966-07-15 NL NL6609988A patent/NL6609988A/xx unknown
- 1966-07-15 NO NO16395066A patent/NO116055B/no unknown
Also Published As
| Publication number | Publication date |
|---|---|
| BE684164A (en) | 1966-12-16 |
| GB1148677A (en) | 1969-04-16 |
| CH441190A (en) | 1967-08-15 |
| NL6609988A (en) | 1967-01-17 |
| DE1497348A1 (en) | 1969-09-25 |
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