NO129247B - - Google Patents
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- Publication number
- NO129247B NO129247B NO420569A NO420569A NO129247B NO 129247 B NO129247 B NO 129247B NO 420569 A NO420569 A NO 420569A NO 420569 A NO420569 A NO 420569A NO 129247 B NO129247 B NO 129247B
- Authority
- NO
- Norway
- Prior art keywords
- benzo
- quinolizine
- hexahydro
- ether
- hydroxy
- Prior art date
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- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 29
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 claims description 18
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical group OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 16
- -1 organometallic acetylene compound Chemical class 0.000 claims description 12
- 239000003054 catalyst Substances 0.000 claims description 9
- 125000000217 alkyl group Chemical group 0.000 claims description 8
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims description 7
- HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 claims description 7
- 239000001257 hydrogen Substances 0.000 claims description 7
- 229910052739 hydrogen Inorganic materials 0.000 claims description 7
- 238000000034 method Methods 0.000 claims description 7
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 6
- 238000006243 chemical reaction Methods 0.000 claims description 6
- 238000002360 preparation method Methods 0.000 claims description 6
- 150000003839 salts Chemical class 0.000 claims description 6
- 125000003342 alkenyl group Chemical group 0.000 claims description 5
- 150000001875 compounds Chemical class 0.000 claims description 5
- 125000003545 alkoxy group Chemical group 0.000 claims description 4
- RDOXTESZEPMUJZ-UHFFFAOYSA-N anisole Chemical compound COC1=CC=CC=C1 RDOXTESZEPMUJZ-UHFFFAOYSA-N 0.000 claims description 4
- 125000005530 alkylenedioxy group Chemical group 0.000 claims description 3
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 3
- 125000003118 aryl group Chemical group 0.000 claims description 3
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 3
- 239000001301 oxygen Substances 0.000 claims description 3
- 229910052760 oxygen Inorganic materials 0.000 claims description 3
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 3
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims description 2
- HPNOEHPRGBNPSI-UHFFFAOYSA-N 6H-benzo[a]quinolizin-2-ol Chemical class OC=1C=CN2CC=C3C(=C2C=1)C=CC=C3 HPNOEHPRGBNPSI-UHFFFAOYSA-N 0.000 claims description 2
- GANUIJNXRUUOPR-UHFFFAOYSA-N benzo[a]quinolizin-2-one Chemical compound C1=CC=C2C3=CC(=O)C=CN3C=CC2=C1 GANUIJNXRUUOPR-UHFFFAOYSA-N 0.000 claims description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 2
- 150000004677 hydrates Chemical class 0.000 claims description 2
- UZKWTJUDCOPSNM-UHFFFAOYSA-N methoxybenzene Substances CCCCOC=C UZKWTJUDCOPSNM-UHFFFAOYSA-N 0.000 claims description 2
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 claims description 2
- 229920002554 vinyl polymer Polymers 0.000 claims description 2
- 238000009833 condensation Methods 0.000 claims 2
- 230000005494 condensation Effects 0.000 claims 2
- 229910052783 alkali metal Inorganic materials 0.000 claims 1
- 150000001340 alkali metals Chemical class 0.000 claims 1
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 30
- 239000000243 solution Substances 0.000 description 21
- 239000000155 melt Substances 0.000 description 18
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 16
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 12
- 230000008018 melting Effects 0.000 description 11
- 238000002844 melting Methods 0.000 description 11
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 9
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 7
- 238000009903 catalytic hydrogenation reaction Methods 0.000 description 7
- 229910052744 lithium Inorganic materials 0.000 description 7
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
- 230000001476 alcoholic effect Effects 0.000 description 6
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 6
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 6
- 238000010521 absorption reaction Methods 0.000 description 5
- UEXCJVNBTNXOEH-UHFFFAOYSA-N Ethynylbenzene Chemical group C#CC1=CC=CC=C1 UEXCJVNBTNXOEH-UHFFFAOYSA-N 0.000 description 4
- 229910021529 ammonia Inorganic materials 0.000 description 4
- 238000004042 decolorization Methods 0.000 description 4
- 238000001704 evaporation Methods 0.000 description 4
- 230000008020 evaporation Effects 0.000 description 4
- 239000007789 gas Substances 0.000 description 4
- 150000002431 hydrogen Chemical class 0.000 description 4
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical class [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 238000004090 dissolution Methods 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- 125000001424 substituent group Chemical group 0.000 description 3
- GDRVFDDBLLKWRI-UHFFFAOYSA-N 4H-quinolizine Chemical compound C1=CC=CN2CC=CC=C21 GDRVFDDBLLKWRI-UHFFFAOYSA-N 0.000 description 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 125000000304 alkynyl group Chemical group 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 239000002585 base Substances 0.000 description 2
- 125000004432 carbon atom Chemical group C* 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- MDKXBBPLEGPIRI-UHFFFAOYSA-N ethoxyethane;methanol Chemical compound OC.CCOCC MDKXBBPLEGPIRI-UHFFFAOYSA-N 0.000 description 2
- 239000012458 free base Substances 0.000 description 2
- WQFXFJBXDHKAKY-UHFFFAOYSA-L magnesium ethynylbenzene dibromide Chemical compound [Mg+2].[Br-].[Br-].C#CC1=CC=CC=C1 WQFXFJBXDHKAKY-UHFFFAOYSA-L 0.000 description 2
- OYICOGPBEIHJEO-UHFFFAOYSA-L magnesium;acetylene;dibromide Chemical compound [Mg+2].[Br-].[Br-].C#C OYICOGPBEIHJEO-UHFFFAOYSA-L 0.000 description 2
- MUMZUERVLWJKNR-UHFFFAOYSA-N oxoplatinum Chemical compound [Pt]=O MUMZUERVLWJKNR-UHFFFAOYSA-N 0.000 description 2
- 239000003208 petroleum Substances 0.000 description 2
- 229910003446 platinum oxide Inorganic materials 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- TVDSBUOJIPERQY-UHFFFAOYSA-N prop-2-yn-1-ol Chemical compound OCC#C TVDSBUOJIPERQY-UHFFFAOYSA-N 0.000 description 2
- QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 description 2
- 229910052938 sodium sulfate Inorganic materials 0.000 description 2
- 235000011152 sodium sulphate Nutrition 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- DURPTKYDGMDSBL-UHFFFAOYSA-N 1-butoxybutane Chemical compound CCCCOCCCC DURPTKYDGMDSBL-UHFFFAOYSA-N 0.000 description 1
- SDMLPLSHKDLKLC-UHFFFAOYSA-N 1-ethynoxybutane Chemical group CCCCOC#C SDMLPLSHKDLKLC-UHFFFAOYSA-N 0.000 description 1
- PTTPXKJBFFKCEK-UHFFFAOYSA-N 2-Methyl-4-heptanone Chemical compound CC(C)CC(=O)CC(C)C PTTPXKJBFFKCEK-UHFFFAOYSA-N 0.000 description 1
- 125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 description 1
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
- CXDIPZOEHIFPBF-UHFFFAOYSA-N 3-butyl-9,10-dimethoxy-1,3,4,6,7,11b-hexahydrobenzo[a]quinolizin-2-one Chemical compound C1CC2=CC(OC)=C(OC)C=C2C2N1CC(CCCC)C(=O)C2 CXDIPZOEHIFPBF-UHFFFAOYSA-N 0.000 description 1
- JMDPBIGEKKWQLF-UHFFFAOYSA-N 9,10-dimethoxy-2,3,4,6,7,11b-hexahydro-1h-benzo[a]quinolizine Chemical compound C1CN2CCCCC2C2=C1C=C(OC)C(OC)=C2 JMDPBIGEKKWQLF-UHFFFAOYSA-N 0.000 description 1
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- 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 1
- 239000007868 Raney catalyst Substances 0.000 description 1
- 229910000564 Raney nickel Inorganic materials 0.000 description 1
- NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 1
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 1
- 208000010513 Stupor Diseases 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- ABIBCFTYJDONHE-UHFFFAOYSA-N [Mg].C#C Chemical compound [Mg].C#C ABIBCFTYJDONHE-UHFFFAOYSA-N 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 150000001447 alkali salts Chemical class 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 235000019270 ammonium chloride Nutrition 0.000 description 1
- 150000005840 aryl radicals Chemical class 0.000 description 1
- 150000007514 bases Chemical class 0.000 description 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 239000001110 calcium chloride Substances 0.000 description 1
- 229910001628 calcium chloride Inorganic materials 0.000 description 1
- 239000007859 condensation product Substances 0.000 description 1
- VWWMOACCGFHMEV-UHFFFAOYSA-N dicarbide(2-) Chemical compound [C-]#[C-] VWWMOACCGFHMEV-UHFFFAOYSA-N 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- PSLIMVZEAPALCD-UHFFFAOYSA-N ethanol;ethoxyethane Chemical compound CCO.CCOCC PSLIMVZEAPALCD-UHFFFAOYSA-N 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 150000004820 halides Chemical class 0.000 description 1
- 230000036571 hydration Effects 0.000 description 1
- 238000006703 hydration reaction Methods 0.000 description 1
- 238000005984 hydrogenation reaction Methods 0.000 description 1
- 239000013067 intermediate product Substances 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 239000011981 lindlar catalyst Substances 0.000 description 1
- ARNWQMJQALNBBV-UHFFFAOYSA-N lithium carbide Chemical compound [Li+].[Li+].[C-]#[C-] ARNWQMJQALNBBV-UHFFFAOYSA-N 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- SFDZETWZUCDYMD-UHFFFAOYSA-N monosodium acetylide Chemical compound [Na+].[C-]#C SFDZETWZUCDYMD-UHFFFAOYSA-N 0.000 description 1
- 239000012452 mother liquor Substances 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- TWNQGVIAIRXVLR-UHFFFAOYSA-N oxo(oxoalumanyloxy)alumane Chemical compound O=[Al]O[Al]=O TWNQGVIAIRXVLR-UHFFFAOYSA-N 0.000 description 1
- 238000004816 paper chromatography Methods 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 1
- MWWATHDPGQKSAR-UHFFFAOYSA-N propyne Chemical group CC#C MWWATHDPGQKSAR-UHFFFAOYSA-N 0.000 description 1
- 229940080360 rauwolfia alkaloid Drugs 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 229940076279 serotonin Drugs 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 238000010626 work up procedure Methods 0.000 description 1
Classifications
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B65—CONVEYING; PACKING; STORING; HANDLING THIN OR FILAMENTARY MATERIAL
- B65D—CONTAINERS FOR STORAGE OR TRANSPORT OF ARTICLES OR MATERIALS, e.g. BAGS, BARRELS, BOTTLES, BOXES, CANS, CARTONS, CRATES, DRUMS, JARS, TANKS, HOPPERS, FORWARDING CONTAINERS; ACCESSORIES, CLOSURES, OR FITTINGS THEREFOR; PACKAGING ELEMENTS; PACKAGES
- B65D21/00—Nestable, stackable or joinable containers; Containers of variable capacity
- B65D21/02—Containers specially shaped, or provided with fittings or attachments, to facilitate nesting, stacking, or joining together
- B65D21/06—Containers specially shaped, or provided with fittings or attachments, to facilitate nesting, stacking, or joining together with movable parts adapted to be placed in alternative positions for nesting the containers when empty and for stacking them when full
- B65D21/062—Containers specially shaped, or provided with fittings or attachments, to facilitate nesting, stacking, or joining together with movable parts adapted to be placed in alternative positions for nesting the containers when empty and for stacking them when full the movable parts being attached or integral and displaceable into a position overlying the top of the container, e.g. bails, corner plates
Landscapes
- Engineering & Computer Science (AREA)
- Mechanical Engineering (AREA)
- Stackable Containers (AREA)
- Details Of Rigid Or Semi-Rigid Containers (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Description
Fremgangsmåte for fremstilling av tertiære benzochinolizinkarbinoler. Process for the preparation of tertiary benzoquinolizine carbinols.
Foreliggende oppfinnelse angår en The present invention relates to a
fremgangsmåte for fremstilling av substituerte 2-hydroksy-benzo (a) chinoliziner process for the preparation of substituted 2-hydroxy-benzo (a) quinolizines
med den generelle formel with the general formula
hvor Ri og R2 betyr vannstoff, en alkoksy-gruppe eller sammen en alkylendioksygruppe, Rs en alkenyl-, aralkyl- eller eventuelt en alkylrest som inneholder eterliknende bundet surstoff, og R+ en eventuelt med alkyl-, aryl- eller alkoksyradikaler substituert etinyl-, henh. vinyl- henh. etylrest, og salter av disse forbindelser. Alkyloksygruppene forannevnt skal, forsåvidt angår substituentene Ri, Ro og R4, fortrinsvis inneholde 1 til 4 carbonatomer. Forsåvidt substituentene Ri og R2 betyr en alkylendioksygruppe skal denne om-fatte metylendioksy- og etylendioksygrup-pen. Alkyl- og alkenylgruppene represen-tert ved substituentene Ra og Ri skal fortrinsvis inneholde 1 til 6 carbonatomer og når fortrinsvis R3 betyr en aralkylgruppe betegner Rs fortrinsvis benzyl- eller fene-tylresten. Når R4 betyr et arylradikal kan dette f. eks. være fenylresten. Fremgangsmåten ifølge oppfinnelsen består i at man omsetter et 2-okso-benzo-(a)chinolizin med den generelle formel where Ri and R2 mean hydrogen, an alkoxy group or together an alkylenedioxy group, Rs an alkenyl-, aralkyl- or optionally an alkyl residue containing an ether-like bound oxygen, and R+ an optionally substituted with alkyl-, aryl- or alkoxy radicals ethynyl-, henh . vinyl acc. ethyl residue, and salts of these compounds. The alkyloxy groups mentioned above must, insofar as the substituents Ri, Ro and R4 are concerned, preferably contain 1 to 4 carbon atoms. Provided that the substituents Ri and R2 mean an alkylenedioxy group, this shall include the methylenedioxy and ethylenedioxy group. The alkyl and alkenyl groups represented by the substituents Ra and Ri should preferably contain 1 to 6 carbon atoms and when R 3 preferably means an aralkyl group, R s preferably denotes the benzyl or phenethyl residue. When R4 denotes an aryl radical, this can e.g. be the phenyl residue. The method according to the invention consists in reacting a 2-oxo-benzo-(a)quinolizine with the general formula
hvor Ri, Ri> og Ra har den foran angitte betydning, med en metallorganisk acetylenforbindelse, hydrolyserer kondensasjons-produktet, hydrerer den oppståtte tertiære karbinol hvis ønsket katalytisk og over-fører eventuelt i et salt. where Ri, Ri> and Ra have the meaning indicated above, with an organometallic acetylene compound, hydrolyzes the condensation product, hydrates the resulting tertiary carbinol if desired catalytically and optionally converts it into a salt.
Fremstillingen av de som utgangsma-terialer nødvendig chinolizinketoner som i den aromatiske ring kan bære en eller to eventuelt seg imellom forbundne alkoksy-grupper og i 3-stillingen er substituert med en alkyl-, alkenyl- eller aralkylrest, som eventuelt kan inneholde eterliknende bundet surstoff, kan skje ifølge angivelsen i Heiv. Chim. Acta 49, (1958), 119 ff. The production of the quinolizine ketones required as starting materials, which in the aromatic ring may carry one or two optionally interconnected alkoxy groups and are substituted in the 3-position with an alkyl, alkenyl or aralkyl residue, which may optionally contain ether-like bound oxygen , can take place according to the information in Heiv. Chim. Acta 49, (1958), 119 ff.
Ifølge oppfinnelsen omsettes disse chinolizinketoner med en metallorganisk acetylenforbindelse, hvis etinylrest kan være substituert med alkyl-, aryl- eller alkoksyradikaler. Eksempler på slike metall-organiske acetylenforbindelser er litium-acetylid, natriumacetylid, acetylen-magne-siumbromid, alkalisalter av alkoksyacety-len og fenylacetylen, fenylacetylenmagne-siumbromid. Omsetningen gjennomføres fortrinsvis i et oppløsningsmiddel. For al-kaliacetylid egner seg særlig flytende ammoniakk, for acetylenmagnesiumhalogeni-der eter, tetrahydrofuran, dioksan og anisol. Alkinyl-karbinolene utvinnes ved for-dampning av oppløsningsmidlet og krystalliseres f. eks. fra diisopropyleter eller di-n-butyleter. According to the invention, these quinolizine ketones are reacted with an organometallic acetylene compound, the ethynyl residue of which can be substituted with alkyl, aryl or alkoxy radicals. Examples of such metal-organic acetylene compounds are lithium acetylide, sodium acetylide, acetylene magnesium bromide, alkali salts of alkoxyacetylene and phenylacetylene, phenylacetylene magnesium bromide. The reaction is preferably carried out in a solvent. For alkali acetylide liquid ammonia is particularly suitable, for acetylene magnesium halides ether, tetrahydrofuran, dioxane and anisole. The alkynyl carbinols are recovered by evaporation of the solvent and crystallized, e.g. from diisopropyl ether or di-n-butyl ether.
For overføring i alkenyl- eller alkyl-karbinoler behandles alkinyl-karbinolene med vannstoff i et egnet oppløsningsmid-del, som f. eks. alkohol eller eddikester, i nærvær av en hydreringskatalysator, som f. eks. platinoksyd, Raney-nikkel, palladiumkull eller Lindlar-katalysator. For conversion into alkenyl or alkyl carbinols, the alkynyl carbinols are treated with hydrogen in a suitable solvent, such as e.g. alcohol or acetic acid, in the presence of a hydrogenation catalyst, such as e.g. platinum oxide, Raney nickel, palladium charcoal or Lindlar catalyst.
De tertiære karbinoler er fargeløse, krystallinske basiske forbindelser. De er litt oppløselige i vann, danner imidlertid med de vanlige organiske eller uorganiske syrer, som f. eks. vinsyre, sitronsyre, fos-forsyre, svovelsyre, metansulfosyre, brom-vannstoffsyre eller saltsyre, i vann oppløse-lige krstallinske salter. Såvel basene som saltene utmerker seg ved sterk narkose-potensierende virkning og frigjør seroto-nin i hjernen. Det resulterer således et liknende virknings-spektrum som visse rauwolfia-alkaloider. De skal finne anven-delse som legemiddel eller som mellompro-dukt for syntese av legemidler. The tertiary carbinols are colorless, crystalline basic compounds. They are slightly soluble in water, but form with the usual organic or inorganic acids, such as e.g. tartaric acid, citric acid, phosphoric acid, sulfuric acid, methanesulfonic acid, hydrobromic acid or hydrochloric acid, water-soluble crystalline salts. Both the bases and the salts are distinguished by their strong narcosis-potentiating effect and release serotonin in the brain. This results in a similar spectrum of action to certain rauwolfia alkaloids. They must find use as a medicine or as an intermediate product for the synthesis of medicines.
De tertiære karbinoler kan oppnåes i forskjellige isomere former. Foreliggende oppfinnelse omfatter fremstillingen av alle dannete isomerer. The tertiary carbinols can be obtained in different isomeric forms. The present invention encompasses the preparation of all isomers formed.
Eksempel 1: Example 1:
I en oppløsning- av 1,7 g litium i 1 000 cm<3> flytende ammoniakk innføres acetylengass inntil den til å begynne med blå oppløsning er avfarget. Derpå tilsettes en oppløsning på 35 g 2-okso-3-etyl-9, 10-dimetoksy-1, 2, 3, 4, 6, 7-heksahydro-llbH-benzo(a)chinolizin i 1200 cm:! absolutt eter, og reaksjonsblandingen rystes over natt i autoklav ved romtemperatur. Etter av-dampning av ammoniakken rystes den eterliknende oppløsning med mettet am-moniumkloridoppløsning, vaskes derpå med vann, tørres over natriumsulfat og derpå inndampes i vakuum. Resten oppløses i aceton, og alkoholisk saltsyreoppløsning tilsettes inntil lakmussur reaksjon. 38 g av et hydroklorid krystalliserer, som etter gjenoppløsningen fra metanoleter smelter ved 257—259° C. Det fra den vandige opp-løsning av hydroklorid ved tilsetning av sodaoppløsning utskilte 2-hydroksy-2-etinyl-3-etyl-9, 10-dimetoksy-l, 2, 3, 4, 6, 7-heksahydro-llbH-benzo(a)-chinolizin smelter etter tørring og gjenoppløsning fra eddikester ved 150° C. Acetylene gas is introduced into a solution of 1.7 g of lithium in 1,000 cm<3> of liquid ammonia until the initially blue solution is decoloured. A solution of 35 g of 2-oxo-3-ethyl-9, 10-dimethoxy-1, 2, 3, 4, 6, 7-hexahydro-IIbH-benzo(a)quinolizine is then added in 1200 cm:! absolute ether, and the reaction mixture is shaken overnight in an autoclave at room temperature. After evaporation of the ammonia, the ether-like solution is shaken with a saturated ammonium chloride solution, then washed with water, dried over sodium sulfate and then evaporated in a vacuum. The residue is dissolved in acetone, and alcoholic hydrochloric acid solution is added until a litmus acid reaction occurs. 38 g of a hydrochloride crystallises, which after redissolution from methanol ether melts at 257-259° C. The 2-hydroxy-2-ethynyl-3-ethyl-9, 10- Dimethoxy-1, 2, 3, 4, 6, 7-hexahydro-IIbH-benzo(a)-quinolizine melts after drying and redissolving from acetic acid at 150°C.
15,8 g av hydrokloridet av 2-hydroksy-2-etinyl-3-etyl-9, 10-dimetoksy-l, 2, 3, 4, 6, 7 - heksahydro-llbH-benzo(a)-chinolizin 15.8 g of the hydrochloride of 2-hydroxy-2-ethynyl-3-ethyl-9, 10-dimethoxy-1, 2, 3, 4, 6, 7-hexahydro-IIbH-benzo(a)-quinolizine
oppløses i 200 cm3 etanol og hydreres over 5 g palladiumkullkatalysator (5 %). Etter dissolve in 200 cm3 of ethanol and hydrate over 5 g of palladium charcoal catalyst (5%). After
opptagelse av 2 mol vannstoff skilles katalysatoren fra, konsentreres, kokes med aceton, nutsjes og gjenoppløses fra etanol-eter. Man får 13,5 g 2-hydroksy-2, 3-dietyl-9, 10-dimetoksy-, 2, 3, 4, 6, 7-heksahydro-1 lbH-benzo (a) chinolizin-hy droklorid med uptake of 2 moles of hydrogen, the catalyst is separated, concentrated, boiled with acetone, cooled and redissolved from ethanol-ether. 13.5 g of 2-hydroxy-2, 3-diethyl-9, 10-dimethoxy-, 2, 3, 4, 6, 7-hexahydro-1 lbH-benzo (a) quinolizine hydrochloride are obtained with
smeltepunkt 192—194° C. Den fra den vandige oppløsning av hydrokloridet med so-daoppløsning fraskilte krystallinske base smelter etter tørring og gjenoppløsning fra isopropyleter fra 124—125° C. melting point 192-194° C. The crystalline base separated from the aqueous solution of the hydrochloride with soda solution melts after drying and redissolving from isopropyl ether from 124-125° C.
Eksempel 2: Example 2:
Til en oppløsning av 470 mg litium i 300 cm<8> flytende ammoniakk innføres ace-tylen inntil avfargning. Derpå tilsetter man en oppløsning av 22 g 2-okso-3-isobutyl-9, 10-dlmetoksy-l, 2, 3, 4, 6, 7-heksahydro-llbH-benzo(a)chinolizin i 1500 cm<:i> absolutt eter. Man ryster over natt i autoklav og arbeider derpå etter angivelsene i eksempel 1. Etter oppløsningen av resten i isopropyleter krystalliserer spontant 16 g 2- -hydroksy-2-etinyl-3-isobutyl-9, 10-dimetoksy-l, 2, 3, 4, 6, 7-heksahydro-llbH-benzo(a)chinolizin med smeltepunkt 124— 125° C. Det i aceton med alkohol-saltsyre fremstilte hydroklorid smelter ved 251— 252° C under sværtning. To a solution of 470 mg of lithium in 300 cm<8> of liquid ammonia, acetylene is introduced until decolourisation. A solution of 22 g of 2-oxo-3-isobutyl-9, 10-dimethoxy-1, 2, 3, 4, 6, 7-hexahydro-IIbH-benzo(a)quinolizine in 1500 cm<:i> is then added. absolute ether. Shake overnight in an autoclave and then proceed according to the instructions in example 1. After dissolving the residue in isopropyl ether, 16 g of 2-hydroxy-2-ethynyl-3-isobutyl-9, 10-dimethoxy-1, 2, 3, 4, 6, 7-hexahydro-IIbH-benzo(a)quinolizine with melting point 124-125° C. The hydrochloride prepared in acetone with alcohol-hydrochloric acid melts at 251-252° C under blackening.
Den katalytiske hydrering av 2-hydroksy - 2-etinyl - 3-isobutyl-9, 10-dimetoksy-l, 2, 3, 4, 6, 7-heksahydro-llbH-benzo(a)chinolizin-hydroklorid gir tilsvarende angivelsene i eksempel 1 2-hydroksy-2-e-tyl-3-isobutyl-9, 10-dimetoksy- 1, 2, 3, 4, 6, 7-heksahydro-1 lbH-benzo (a) chinolizin-hydroklorid med smeltepunkt 216—218° C. Den fra den vandige oppløsning av hydrokloridet på vanlig måte utskilte frie base smelter etter gjenoppløsning fra isopropyleter ved 121—122° C. The catalytic hydrogenation of 2-hydroxy - 2-ethynyl - 3-isobutyl-9, 10-dimethoxy-1, 2, 3, 4, 6, 7-hexahydro-IIbH-benzo(a)quinolizine hydrochloride gives corresponding to the indications in example 1 2-Hydroxy-2-ethyl-3-isobutyl-9, 10-dimethoxy-1, 2, 3, 4, 6, 7-hexahydro-1 lbH-benzo (a) quinolizine hydrochloride with melting point 216—218 ° C. The free base separated from the aqueous solution of the hydrochloride in the usual way melts after redissolving from isopropyl ether at 121-122° C.
Eksempel 3: Example 3:
6,8 g av det etter angivelsene i eksempel 2 2-hydroksy-2-etinyl-3-isobutyl-9, 10-dimetoksy-l, 2, 3, 4, 6, 7-heksahydro-ll bH-benzo(a)chinolizin oppløses i 100 cm<3 >metanol og hydreres over 2 g palladiumkull-katalysator inntil opptagelse av 1 mol vannstoff. I løpet av 35 min. opptas 490 cm<3>. Etter avfiltrering av katalysatoren og inndampning krystalliseres fra diisopropyleter. Man får 5,1 g 2-hydroksy-2-vinyl-3- isobutyl-:9,10-dimetoksy-l, 2, 3, 4, 6, 7-heksahydro-1 lbH-benzo (a) chinolizin med smeltepunkt 86° C. Det i aceton med alkoholisk saltsyre fremstilte hydroklorid smelter ved 244—245° C. 6.8 g of it according to the indications in example 2 2-hydroxy-2-ethynyl-3-isobutyl-9, 10-dimethoxy-1, 2, 3, 4, 6, 7-hexahydro-11 bH-benzo(a) quinolizine is dissolved in 100 cm<3 >methanol and hydrated over 2 g of palladium charcoal catalyst until 1 mol of water is absorbed. Within 35 min. 490 cm<3> is recorded. After filtering off the catalyst and evaporation, crystallize from diisopropyl ether. 5.1 g of 2-hydroxy-2-vinyl-3-isobutyl-:9,10-dimethoxy-1, 2, 3, 4, 6, 7-hexahydro-1 lbH-benzo (a) quinolizine with a melting point of 86 ° C. The hydrochloride prepared in acetone with alcoholic hydrochloric acid melts at 244-245° C.
Viderehydreringen fører under opptagelse av 1 mol vannstoff til den i eksempel 2 beskrevne etylkarbinol. The further hydration leads to the ethylcarbinol described in example 2, with the absorption of 1 mol of hydrogen.
Eksempel 4: Example 4:
I en oppløsning av 1,6 g natrium i 250 cm:! flytende ammoniakk innføres tørret acetylengass inntil oppløsningen er avfarget. Derpå tilsettes en oppløsning av 11 g 2-okso-3-isobutyl-9,10-dimetoksy-l, 2, 3, 4, 6, 7-heksahydro-llbH-benzo(a)chinolizin i 750 cm<3> absolutt eter og røres om i to timer. Over natt dampes ammoniakk under stadig omrøring av. Resten tilsettes mettet vandig ammoniumklorid-oppløs-ning, den eteriske oppløsning skilles fra, vaskes med vann, tørres over natriumsulfat og konsentreres. Resten gir etter opptagelse i diisopropyleter 6,5 g etinylkarbi-nol med smeltepunkt 125° C, som er iden-tisk med det etter eksempel 2 fremstilte preparat. I moderluten kan papirkromato-grafisk en isomer forbindelse påvises. In a solution of 1.6 g of sodium in 250 cm:! liquid ammonia, dry acetylene gas is introduced until the solution is decoloured. A solution of 11 g of 2-oxo-3-isobutyl-9,10-dimethoxy-1, 2, 3, 4, 6, 7-hexahydro-IIbH-benzo(a)quinolizine in 750 cm<3> of absolute ether is then added. and stirred for two hours. Ammonia is evaporated overnight with constant stirring. Saturated aqueous ammonium chloride solution is added to the residue, the ethereal solution is separated, washed with water, dried over sodium sulphate and concentrated. After absorption in diisopropyl ether, the residue gives 6.5 g of ethynylcarbinol with a melting point of 125° C., which is identical to the preparation prepared according to example 2. In the mother liquor, an isomeric compound can be detected using paper chromatography.
Til samme produkt fører også omsetningen av ketonet med acetylenmonomag-nesiumbromid (J. Chem. Soc. (London) 1956, 4765), hvorved likeledes en blanding av de to isomere etinylkarbinoler oppnåes. The reaction of the ketone with acetylene monomagnesium bromide (J. Chem. Soc. (London) 1956, 4765) also leads to the same product, whereby a mixture of the two isomeric ethynyl carbinols is likewise obtained.
I IN
Eksempel 5: Example 5:
500 mg litium oppløses i 250 cm<8> flytende ammoniakk og etterpå ledes metyl-acetylen som på forhånd er blitt tørret med kalsiumklorid inntil avfargning inn. Derpå tilføres 11 g 2-okso-3-isobutyl-9,10-dimetoksy-l, 2, 3, 4, 6, 7-heksahydro-llbH-benzo(a)chinolizin, som er oppløst i 700 cm<:i> absolutt eter. Etter 2 timers omrøring får det henstå over natt, hvorved ammoniakken fordamper. Det opparbeides etter angivelsene i eksempel 4. Man får 9,5 g 2-hydroksy-2-metyletinyl-3-isobutyl-9,10-dimetoksy-l, 2, 3, 4, 6, 7-heksahydro-llbH-benzo(a)chinolizin med smeltepunkt 154° C. Det i aceton med alkoholisk saltsyre fremstilte hydroklorid smelter ved 221 —222° C. Ved den katalytiske hydrering av 3,9 g av den foranstående forbindelse i 100 cm3 metanol over 200 mg platinaoksyd-katalysator opptas den for opptagelse av 2 mol beregnet mengde vannstoff. Det etter inndampning fra diisoopropyleter krystal-liserende 2-hydroksy-2-propyl-3-isobutyl-9, 10-dimetoksy-l, 2, 3, 4, 6, 7-heksahydro-1 lbH-benzo (a) chinolizin smelter etter gjenoppløsning fra eddikester ved 117° C. Hydroklorid smeltepunkt 198—200° C. 500 mg of lithium is dissolved in 250 cm<8> of liquid ammonia and afterwards methyl-acetylene which has been dried with calcium chloride until decolourisation is introduced. 11 g of 2-oxo-3-isobutyl-9,10-dimethoxy-1, 2, 3, 4, 6, 7-hexahydro-IIbH-benzo(a)quinolizine, which is dissolved in 700 cm<:i> absolute ether. After 2 hours of stirring, it is allowed to stand overnight, whereby the ammonia evaporates. It is processed according to the instructions in example 4. 9.5 g of 2-hydroxy-2-methylethynyl-3-isobutyl-9,10-dimethoxy-1, 2, 3, 4, 6, 7-hexahydro-IIbH-benzo( a) quinolizine with a melting point of 154° C. The hydrochloride prepared in acetone with alcoholic hydrochloric acid melts at 221-222° C. In the catalytic hydrogenation of 3.9 g of the above compound in 100 cm3 of methanol over 200 mg of platinum oxide catalyst, the for absorption of 2 moles of calculated amount of water. After evaporation from diisopropyl ether crystallising 2-hydroxy-2-propyl-3-isobutyl-9, 10-dimethoxy-1, 2, 3, 4, 6, 7-hexahydro-1 lbH-benzo (a) quinolizine melts after redissolve from acetic acid at 117° C. Hydrochloride melting point 198-200° C.
Eksempel 6: Example 6:
I en oppløsning på 420 mg litium i 250 cm<8> flytende ammoniakk innføres 5,88 g n-butoksyacetylen og etter to timers om-røring tilsettes en oppløsning på 9,5 g 2-okso-3-isobutyl-9,10-dimetoksy-l, 2, 3, 4, 6, 7-heksahydro-llbH-benzo(a)chinolizin i 700 cm<3> absolutt eter. Den etter angivelsene i eksempel 4 erholdte ekstrakt krystalliserer fra petroleter. Man får 2,8 g 2-hydroksy-2-n-butoksy-etinyl-3-isobutyl - 9, 10-dimetoksy-l,.2, 3, 4, 6, 7-heksahydro-ll bH-benzo(a) chinolizin med smeltepunkt 84 ° C. Den katalytiske hydrering etter de i eksempel 1 angitte betingelser fører til 2-hydroksy-2-n-butoksy-etyl-3-isobutyl-9, 10-dimetoksy-l, 2, 3, 4, 6, 7-heksahydro-.1 lbH-benzo (a) chinolizin, hvis hydroklorid smelter ved 204—205° C. 5.88 g of n-butoxyacetylene are introduced into a solution of 420 mg of lithium in 250 cm<8> of liquid ammonia and, after two hours of stirring, a solution of 9.5 g of 2-oxo-3-isobutyl-9,10- dimethoxy-l, 2, 3, 4, 6, 7-hexahydro-llbH-benzo(a)quinolizine in 700 cm<3> absolute ether. The extract obtained according to the instructions in example 4 crystallizes from petroleum ether. 2.8 g of 2-hydroxy-2-n-butoxy-ethynyl-3-isobutyl - 9, 10-dimethoxy-1,.2, 3, 4, 6, 7-hexahydro-ll bH-benzo(a) is obtained quinolizine with melting point 84 °C. The catalytic hydrogenation according to the conditions stated in example 1 leads to 2-hydroxy-2-n-butoxy-ethyl-3-isobutyl-9, 10-dimethoxy-1, 2, 3, 4, 6 , 7-hexahydro-.1 lbH-benzo (a) quinolizine, the hydrochloride of which melts at 204—205° C.
Eksempel 7: Example 7:
700 mg litium oppløses i 400 cm<:i> flytende ammoniakk og derpå tilsettes drå-pevis 10,2 g fenylacetylen. Det røres om i to timer. Derpå tilsetter man en oppløs-ning av 16 g 2-okso-3-isobutyl-9, 10-dimetoksy-l, 2, 3, 4, 6, 7-heksahydro-llbH-benzo (a) chinolizin i 600 cm<3> absolutt eter. Man lar ammoniakken fordampe over natt, og opparbeider derpå etter angivelsene i eksempel 4. Den erholdte rest oppløses i aceton og tilsettes alkoholisk saltsyre (kongosur). Man får 10 g 2-hydroksy-2-fe-nyletinyl-3-isobutyl-9, 10-dimetoksy-l, 2, 3, 4, 6, 7-heksahydro-llbH-benzo(a)chinoli-zinhydroklorid med smeltepunkt 240° C. 700 mg of lithium is dissolved in 400 cm<:i> of liquid ammonia and then 10.2 g of phenylacetylene is added dropwise. It is stirred for two hours. A solution of 16 g of 2-oxo-3-isobutyl-9, 10-dimethoxy-1, 2, 3, 4, 6, 7-hexahydro-IIbH-benzo (a) quinolizine is then added in 600 cm<3 > absolute ether. The ammonia is allowed to evaporate overnight, and then processed according to the instructions in example 4. The residue obtained is dissolved in acetone and alcoholic hydrochloric acid (congo acid) is added. 10 g of 2-hydroxy-2-phenylethynyl-3-isobutyl-9, 10-dimethoxy-1, 2, 3, 4, 6, 7-hexahydro-IIbH-benzo(a)quinolizine hydrochloride with a melting point of 240 °C.
Til samme produkt kommer man, når man omsettes isobutylketonet i tetrahydrofuran med fenylacetylenmagnesiumbro-mid (J. Chem. Soc, 1956, 4765). Ved siden av fåes en stereoisomer forbindelse, hvis hydroklorid smelter ved 273° C. The same product is obtained when the isobutyl ketone is reacted in tetrahydrofuran with phenylacetylene magnesium bromide (J. Chem. Soc, 1956, 4765). Next to it, a stereoisomeric compound is obtained, the hydrochloride of which melts at 273° C.
Den katalytiske hydrering av 4,56 g 2-hydroksy-2-fenyletinyl-3-isobutyl-9, 10-di-tmetoksy-1, 2, 3, 4, 6, 7-heksahydro-llbH-benzo(a)ichlnolizin-hydroklorid i 70 cm<3 >•metanol over 4 g palladiumkull-katalysator (5 %) gir under opptagelse av 2 mol vannstoff 3,5 g 2-hydroksy-2-fenyletyl-3-isobutyl-9, 10-dimetoksy-l, 2, 3, 4, 6, 7-heksahydro-l lbH-benzo (a) chinolizin-hydroklorid, som etter gjenoppløsning fra metanol-eter smelter ved 235° C. The catalytic hydrogenation of 4.56 g of 2-hydroxy-2-phenylethynyl-3-isobutyl-9, 10-di-tmethoxy-1, 2, 3, 4, 6, 7-hexahydro-llbH-benzo(a)ichlnolizine- hydrochloride in 70 cm<3 >•methanol over 4 g of palladium charcoal catalyst (5%) gives, with the absorption of 2 mol of hydrogen, 3.5 g of 2-hydroxy-2-phenylethyl-3-isobutyl-9, 10-dimethoxy-1, 2, 3, 4, 6, 7-hexahydro-1 lbH-benzo (a) quinolizine hydrochloride, which after redissolving from methanol-ether melts at 235° C.
Eksempel 8: Example 8:
Fra 2-okso-3-n-butyl-9, 10-dimetoksy-1, 2, 3, 4, 6, 7-heksahydro-llbH-benzo(a)-chinolizin fremstilles etter angivelsene i From 2-oxo-3-n-butyl-9, 10-dimethoxy-1, 2, 3, 4, 6, 7-hexahydro-llbH-benzo(a)-quinolizine is prepared according to the instructions in
eksempel 1 2-hydroksy-2-etinyl-3-n-butyl- example 1 2-hydroxy-2-ethynyl-3-n-butyl-
9, 10-dimetoksy-l, 2, 3, 4, 6, 7-heksahydro-llbH-benzo(a)chinolizin. Smeltepunkt 115° 9,10-dimethoxy-1,2,3,4,6,7-hexahydro-11bH-benzo(a)quinolizine. Melting point 115°
C. Det i aceton med alkoholisk saltsyre C. That in acetone with alcoholic hydrochloric acid
fremstilte hydroklorid smelter ved 233— produced hydrochloride melts at 233—
234° C. under svertning. 234° C. during blackening.
Den katalytiske hydrering tilsvarende angivelsene i eksempel 1 fører til 2-hydrok- The catalytic hydrogenation corresponding to the information in example 1 leads to 2-hydroxy
sy-1, 2, 3, 4, 6, 7-heksahydro-llbH-benzo-(a)chinolizin-hydroklorid med smeltepunkt 214° C. Den frie base smelter ved 85° C. sy-1, 2, 3, 4, 6, 7-hexahydro-llbH-benzo-(a)quinolizine hydrochloride with a melting point of 214° C. The free base melts at 85° C.
Eksempel 9: Example 9:
I en oppløsning av 160 mg litium i 100 In a solution of 160 mg lithium in 100
cm3 flytende ammoniakk innføres tørr ace- cm3 of liquid ammonia is introduced into dry ace-
tylengass inntil avfargning. Dertil setter man en oppløsning av 3,2 g 2-okso-3-n-butyl-9-metoksy-l, 2, 3, 4, 6, 7-heksahydro-1 lbH-benzo (a) chinolizin i 200 cm<3> absolutt eter. Etter rystning i autoklav ved romtemperatur over natt opparbeides oven-stemmende med angivelsene i eksempel 4. tylene gas until decolourisation. To this is added a solution of 3.2 g of 2-oxo-3-n-butyl-9-methoxy-1, 2, 3, 4, 6, 7-hexahydro-1 lbH-benzo (a) quinolizine in 200 cm< 3> absolute ether. After shaking in an autoclave at room temperature overnight, work up according to the instructions in example 4 above.
Den erholdte rest (3,0 g) oppløses i benzol The residue obtained (3.0 g) is dissolved in benzene
og kromatograferes på en søyle av 30 g aluminiumoksyd (Akt. II, nøytral). Med benzol kan krystallinsk utgangsmateriale elueres. Med eter elueres totalt 600 mg 2-hydroksy-2-etinyl-3-n-butyl-9-metoksy - 1, and chromatographed on a column of 30 g aluminum oxide (Akt. II, neutral). With benzene, crystalline starting material can be eluted. A total of 600 mg of 2-hydroxy-2-ethynyl-3-n-butyl-9-methoxy - 1 is eluted with ether,
2, 3, 4, 6, 7-heksahydro-llbH-benzo(a)\-chinolizin, som smelter etter gjenoppløs- 2, 3, 4, 6, 7-hexahydro-IIbH-benzo(a)\-quinolizine, which melts after redissolving
ning fra eddikester-petroleter ved 144° C. ning from acetic ester-petroleum ether at 144° C.
200 mg 2-hydroksy-2-etinyl-3-n-butyl-9-metoksy-l, 2, 3, 4, 6, 7-heksahydro-llbH-benzo(a)chinolizin gir ved den katalytiske hydrering over 200 mg palladiumkullkata- 200 mg of 2-hydroxy-2-ethynyl-3-n-butyl-9-methoxy-1, 2, 3, 4, 6, 7-hexahydro-IIbH-benzo(a)quinolizine gives in the catalytic hydrogenation over 200 mg of palladium charcoal -
lysator (5 %) under opptagelse av 2 mol vannstoff 160 mg 2-hydroksy-2-etyl-3-n-butyl-9-metoksy-l, 2, 3, 4, 6, 7-heksahydro-llbH-benzo(a)chinolizin, som etter gjen-oppløsning fra isopropyleter smelter ved 131° C. lysator (5%) while absorbing 2 mol of water 160 mg 2-hydroxy-2-ethyl-3-n-butyl-9-methoxy-1, 2, 3, 4, 6, 7-hexahydro-llbH-benzo(a )quinolizine, which after re-dissolution from isopropyl ether melts at 131° C.
Eksempel 10: Example 10:
I en oppløsning av 130 mg litium i In a solution of 130 mg lithium i
100 cm<3> flytende ammoniakk innføres tørr acetylengass inntil avfargning. Derpå til- 100 cm<3> of liquid ammonia is introduced into dry acetylene gas until decolourisation. Then to-
settes en oppløsning på 3 g 2-okso-3-co-methoksybutyl-9, 10-dimetoksy-l, 2, 3, 4, 6, 7-heksahydro-llbH-benzo(a) chinolizin i 250 cm<3> absolutt eter. Ved viderebehand- a solution of 3 g of 2-oxo-3-co-methoxybutyl-9, 10-dimethoxy-1, 2, 3, 4, 6, 7-hexahydro-llbH-benzo(a) quinolizine is placed in 250 cm<3> absolute ether. In case of further processing
ling etter angivelsene i eksempel 4 får man 3 g av en ekstrakt som etter oppløsning i eter, gir 1,1 g krystallinsk 2-hydroksy-2-etinyl-3-rø-metoksybutyl-9, 10-dimetoksy- following the instructions in example 4, 3 g of an extract are obtained which, after dissolution in ether, gives 1.1 g of crystalline 2-hydroxy-2-ethynyl-3-rho-methoxybutyl-9, 10-dimethoxy-
1, 2, 3, 4, 6, 7-heksahydro-llbH-benzo(a)- 1, 2, 3, 4, 6, 7-hexahydro-llbH-benzo(a)-
chinolizin. Preparatet smelter etter gjen-oppløsning fra eddikester ved 109° C. Det i aceton med alkoholisk saltsyre tilberedte hydroklorid smelter ved 223° C. quinolizine. The preparation melts after re-dissolution from acetic acid at 109° C. The hydrochloride prepared in acetone with alcoholic hydrochloric acid melts at 223° C.
Den katalytiske hydrering av 500 mg 2-hydroksy-2-etinyl-3-co-metoksybutyl-9, 10-dimetoksy-l, 2, 3, 4, 6, 7-heksahydro-ll bH-benzo(a) chinolizin i metanol over 250 The catalytic hydrogenation of 500 mg of 2-hydroxy-2-ethynyl-3-co-methoxybutyl-9, 10-dimethoxy-1, 2, 3, 4, 6, 7-hexahydro-llbH-benzo(a)quinolizine in methanol over 250
mg palladiumkull-katalysator (5 %) gir under opptagelse av 2 mol vannstoff 350 g 2-hydroksy-2-etyl-3-o)-metoksybutyl-9, 10-dimetoksy-l, 2, 3, 4, 6, 7-heksahydro-llbH-benzo(a)chinolizin, som etter gjenoppløs- mg of palladium charcoal catalyst (5%) gives, with the absorption of 2 mol of hydrogen, 350 g of 2-hydroxy-2-ethyl-3-o)-methoxybutyl-9, 10-dimethoxy-1, 2, 3, 4, 6, 7- hexahydro-llbH-benzo(a)quinolizine, which after redissolving
ning fra diisopropyleter smelter ved 98° C. ning from diisopropyl ether melts at 98° C.
Claims (4)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| SE1563368A SE384993B (en) | 1968-11-18 | 1968-11-18 | STACKABLE VARUBACK |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| NO129247B true NO129247B (en) | 1974-03-18 |
Family
ID=20300963
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO420569A NO129247B (en) | 1968-11-18 | 1969-10-22 |
Country Status (10)
| Country | Link |
|---|---|
| AT (1) | AT301437B (en) |
| BE (1) | BE740187A (en) |
| CH (1) | CH506415A (en) |
| DE (1) | DE1951053C3 (en) |
| DK (1) | DK127688B (en) |
| FI (1) | FI48698C (en) |
| GB (1) | GB1287936A (en) |
| NL (1) | NL6917249A (en) |
| NO (1) | NO129247B (en) |
| SE (1) | SE384993B (en) |
Families Citing this family (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB2061227B (en) * | 1979-10-30 | 1983-08-10 | Gpg Int Ltd | Open-fronted container |
| GB8311027D0 (en) * | 1983-04-22 | 1983-05-25 | Drg Uk Ltd | Nestable trays |
| GB2167045B (en) * | 1984-11-21 | 1989-01-05 | Frederick William Paton | Container for cut flowers |
| DE3741350A1 (en) * | 1987-12-07 | 1989-06-15 | Stabernack Gmbh Gustav | Stackable tray |
| GB2216101B (en) * | 1988-03-28 | 1992-10-14 | David Choon Sen Lam | Crates for transporting rubber blocks or sheets |
| NL194076C (en) * | 1992-06-11 | 2001-06-05 | Beekenkamp Tuinbouwtech Bv | Nestable and stackable holder. |
-
1968
- 1968-11-18 SE SE1563368A patent/SE384993B/en unknown
-
1969
- 1969-10-06 DE DE19691951053 patent/DE1951053C3/en not_active Expired
- 1969-10-06 GB GB4891269A patent/GB1287936A/en not_active Expired
- 1969-10-07 AT AT945969A patent/AT301437B/en not_active IP Right Cessation
- 1969-10-09 CH CH1517769A patent/CH506415A/en not_active IP Right Cessation
- 1969-10-13 BE BE740187D patent/BE740187A/xx unknown
- 1969-10-22 NO NO420569A patent/NO129247B/no unknown
- 1969-10-29 FI FI310669A patent/FI48698C/en active
- 1969-11-17 DK DK607069A patent/DK127688B/en unknown
- 1969-11-17 NL NL6917249A patent/NL6917249A/xx unknown
Also Published As
| Publication number | Publication date |
|---|---|
| DE1951053C3 (en) | 1974-11-21 |
| NL6917249A (en) | 1970-05-20 |
| CH506415A (en) | 1971-04-30 |
| GB1287936A (en) | 1972-09-06 |
| BE740187A (en) | 1970-03-16 |
| AT301437B (en) | 1972-09-11 |
| FI48698C (en) | 1974-12-10 |
| DK127688B (en) | 1973-12-17 |
| DE1951053B2 (en) | 1974-01-10 |
| DE1951053A1 (en) | 1970-06-11 |
| SE384993B (en) | 1976-05-31 |
| FI48698B (en) | 1974-09-02 |
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