CA1091675A - No translation available - Google Patents

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Info

Publication number: CA1091675A
Authority: CA; Canada
Prior art keywords: compound; formula; borane; boron; cyclobutyl
Prior art date: 1976-03-23
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.): Expired

Application number

CA339,989A

Other languages

English (en)

Inventor

Gary M.F. Lim

Henry Wong

Ivo Monkovic

Carol Bachand

Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)

Bristol Myers Squibb Co

Original Assignee

Bristol Myers Squibb Co

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

1976-03-23

Filing date

1979-11-16

Publication date

1980-12-16

1976-03-23 Priority claimed from US05/669,795 external-priority patent/US4058531A/en

1977-02-17 Priority claimed from US05/769,808 external-priority patent/US4139534A/en

1977-03-18 Priority claimed from CA274,241A external-priority patent/CA1086723A/fr

1979-11-16 Application filed by Bristol Myers Squibb Co filed Critical Bristol Myers Squibb Co

1979-11-16 Priority to CA339,989A priority Critical patent/CA1091675A/fr

1980-12-16 Application granted granted Critical

1980-12-16 Publication of CA1091675A publication Critical patent/CA1091675A/fr

Status Expired legal-status Critical Current

Links

NENLYAQPNATJSU-UHFFFAOYSA-N 1,2,3,4,4a,5,6,7,8,8a-decahydroisoquinoline Chemical class C1NCCC2CCCCC21 NENLYAQPNATJSU-UHFFFAOYSA-N 0.000 title abstract description 10
150000001875 compounds Chemical class 0.000 claims abstract description 53
UORVGPXVDQYIDP-UHFFFAOYSA-N borane Chemical compound B UORVGPXVDQYIDP-UHFFFAOYSA-N 0.000 claims abstract description 44
238000000034 method Methods 0.000 claims abstract description 35
229910000085 borane Inorganic materials 0.000 claims abstract description 22
230000008569 process Effects 0.000 claims abstract description 19
125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 16
125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 15
125000000217 alkyl group Chemical group 0.000 claims description 13
229910052796 boron Inorganic materials 0.000 claims description 11
ZOXJGFHDIHLPTG-UHFFFAOYSA-N Boron Chemical compound [B] ZOXJGFHDIHLPTG-UHFFFAOYSA-N 0.000 claims description 10
WTEOIRVLGSZEPR-UHFFFAOYSA-N boron trifluoride Chemical compound FB(F)F WTEOIRVLGSZEPR-UHFFFAOYSA-N 0.000 claims description 8
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 7
238000002360 preparation method Methods 0.000 claims description 7
238000006243 chemical reaction Methods 0.000 claims description 5
239000012279 sodium borohydride Substances 0.000 claims description 5
229910000033 sodium borohydride Inorganic materials 0.000 claims description 5
239000002904 solvent Substances 0.000 claims description 5
229910015900 BF3 Inorganic materials 0.000 claims description 4
MCQRPQCQMGVWIQ-UHFFFAOYSA-N boron;methylsulfanylmethane Chemical compound [B].CSC MCQRPQCQMGVWIQ-UHFFFAOYSA-N 0.000 claims description 3
238000011065 in-situ storage Methods 0.000 claims description 2
CHNLPLHJUPMEOI-UHFFFAOYSA-N oxolane;trifluoroborane Chemical compound FB(F)F.C1CCOC1 CHNLPLHJUPMEOI-UHFFFAOYSA-N 0.000 claims description 2
239000000126 substance Substances 0.000 claims 2
239000002253 acid Substances 0.000 abstract description 11
-1 N-substituted-14-hydroxy-3-substituted-morphinan Chemical class 0.000 abstract description 7
239000007858 starting material Substances 0.000 abstract description 4
238000006257 total synthesis reaction Methods 0.000 abstract description 3
125000004850 cyclobutylmethyl group Chemical group C1(CCC1)C* 0.000 abstract description 2
230000003533 narcotic effect Effects 0.000 abstract description 2
239000000556 agonist Substances 0.000 abstract 2
239000005557 antagonist Substances 0.000 abstract 2
230000000694 effects Effects 0.000 abstract 2
230000003389 potentiating effect Effects 0.000 abstract 2
PSGXTMNRCXHWJR-UHFFFAOYSA-N 2-[(4-methoxyphenyl)methyl]-3,4,5,6,7,8-hexahydro-1h-isoquinoline Chemical compound C1=CC(OC)=CC=C1CN1CC(CCCC2)=C2CC1 PSGXTMNRCXHWJR-UHFFFAOYSA-N 0.000 abstract 1
239000000730 antalgic agent Substances 0.000 abstract 1
229940051807 opiod analgesics morphinan derivative Drugs 0.000 abstract 1
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 33
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 24
239000000203 mixture Substances 0.000 description 19
NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 18
239000000243 solution Substances 0.000 description 17
RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 14
229940073584 methylene chloride Drugs 0.000 description 11
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
229910000147 aluminium phosphate Inorganic materials 0.000 description 9
150000002118 epoxides Chemical group 0.000 description 9
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 9
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 8
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 8
150000002009 diols Chemical class 0.000 description 8
AOJFQRQNPXYVLM-UHFFFAOYSA-N pyridin-1-ium;chloride Chemical compound [Cl-].C1=CC=[NH+]C=C1 AOJFQRQNPXYVLM-UHFFFAOYSA-N 0.000 description 8
INAXVFBXDYWQFN-XHSDSOJGSA-N morphinan Chemical class C1C2=CC=CC=C2[C@]23CCCC[C@H]3[C@@H]1NCC2 INAXVFBXDYWQFN-XHSDSOJGSA-N 0.000 description 7
KFSLWBXXFJQRDL-UHFFFAOYSA-N peroxyacetic acid Substances CC(=O)OO KFSLWBXXFJQRDL-UHFFFAOYSA-N 0.000 description 7
239000011541 reaction mixture Substances 0.000 description 7
DLYUQMMRRRQYAE-UHFFFAOYSA-N tetraphosphorus decaoxide Chemical compound O1P(O2)(=O)OP3(=O)OP1(=O)OP2(=O)O3 DLYUQMMRRRQYAE-UHFFFAOYSA-N 0.000 description 7
FCSKOFQQCWLGMV-UHFFFAOYSA-N 5-{5-[2-chloro-4-(4,5-dihydro-1,3-oxazol-2-yl)phenoxy]pentyl}-3-methylisoxazole Chemical compound O1N=C(C)C=C1CCCCCOC1=CC=C(C=2OCCN=2)C=C1Cl FCSKOFQQCWLGMV-UHFFFAOYSA-N 0.000 description 6
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 6
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 6
239000000047 product Substances 0.000 description 6
238000007363 ring formation reaction Methods 0.000 description 6
150000003839 salts Chemical class 0.000 description 6
230000003287 optical effect Effects 0.000 description 5
238000003756 stirring Methods 0.000 description 5
238000006467 substitution reaction Methods 0.000 description 5
VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 4
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
150000001412 amines Chemical group 0.000 description 4
239000000908 ammonium hydroxide Substances 0.000 description 4
IFKLAQQSCNILHL-QHAWAJNXSA-N butorphanol Chemical compound N1([C@@H]2CC3=CC=C(C=C3[C@@]3([C@]2(CCCC3)O)CC1)O)CC1CCC1 IFKLAQQSCNILHL-QHAWAJNXSA-N 0.000 description 4
239000000543 intermediate Substances 0.000 description 4
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
QMMFVYPAHWMCMS-UHFFFAOYSA-N Dimethyl sulfide Chemical compound CSC QMMFVYPAHWMCMS-UHFFFAOYSA-N 0.000 description 3
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
230000000202 analgesic effect Effects 0.000 description 3
230000015572 biosynthetic process Effects 0.000 description 3
239000003795 chemical substances by application Substances 0.000 description 3
239000000284 extract Substances 0.000 description 3
239000000463 material Substances 0.000 description 3
239000012299 nitrogen atmosphere Substances 0.000 description 3
239000003960 organic solvent Substances 0.000 description 3
230000003647 oxidation Effects 0.000 description 3
238000007254 oxidation reaction Methods 0.000 description 3
239000007787 solid Substances 0.000 description 3
238000003786 synthesis reaction Methods 0.000 description 3
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 3
PAMIQIKDUOTOBW-UHFFFAOYSA-N 1-methylpiperidine Chemical compound CN1CCCCC1 PAMIQIKDUOTOBW-UHFFFAOYSA-N 0.000 description 2
BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 2
QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 2
XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 2
FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 2
MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 2
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 2
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 2
DWAQJAXMDSEUJJ-UHFFFAOYSA-M Sodium bisulfite Chemical compound [Na+].OS([O-])=O DWAQJAXMDSEUJJ-UHFFFAOYSA-M 0.000 description 2
150000007513 acids Chemical class 0.000 description 2
ILAHWRKJUDSMFH-UHFFFAOYSA-N boron tribromide Chemical compound BrB(Br)Br ILAHWRKJUDSMFH-UHFFFAOYSA-N 0.000 description 2
OROGSEYTTFOCAN-DNJOTXNNSA-N codeine Chemical compound C([C@H]1[C@H](N(CC[C@@]112)C)C3)=C[C@H](O)[C@@H]1OC1=C2C3=CC=C1OC OROGSEYTTFOCAN-DNJOTXNNSA-N 0.000 description 2
238000001816 cooling Methods 0.000 description 2
JFWMYCVMQSLLOO-UHFFFAOYSA-N cyclobutanecarbonyl chloride Chemical compound ClC(=O)C1CCC1 JFWMYCVMQSLLOO-UHFFFAOYSA-N 0.000 description 2
239000000706 filtrate Substances 0.000 description 2
ZZUFCTLCJUWOSV-UHFFFAOYSA-N furosemide Chemical compound C1=C(Cl)C(S(=O)(=O)N)=CC(C(O)=O)=C1NCC1=CC=CO1 ZZUFCTLCJUWOSV-UHFFFAOYSA-N 0.000 description 2
239000007789 gas Substances 0.000 description 2
BHEPBYXIRTUNPN-UHFFFAOYSA-N hydridophosphorus(.) (triplet) Chemical compound [PH] BHEPBYXIRTUNPN-UHFFFAOYSA-N 0.000 description 2
IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 2
229910000041 hydrogen chloride Inorganic materials 0.000 description 2
230000007062 hydrolysis Effects 0.000 description 2
238000006460 hydrolysis reaction Methods 0.000 description 2
150000002500 ions Chemical class 0.000 description 2
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 2
BQJCRHHNABKAKU-KBQPJGBKSA-N morphine Chemical compound O([C@H]1[C@H](C=C[C@H]23)O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4O BQJCRHHNABKAKU-KBQPJGBKSA-N 0.000 description 2
231100000252 nontoxic Toxicity 0.000 description 2
230000003000 nontoxic effect Effects 0.000 description 2
238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 2
150000004965 peroxy acids Chemical class 0.000 description 2
239000012071 phase Substances 0.000 description 2
238000003822 preparative gas chromatography Methods 0.000 description 2
238000006722 reduction reaction Methods 0.000 description 2
238000010992 reflux Methods 0.000 description 2
239000011734 sodium Substances 0.000 description 2
229910052708 sodium Inorganic materials 0.000 description 2
235000010267 sodium hydrogen sulphite Nutrition 0.000 description 2
QAEDZJGFFMLHHQ-UHFFFAOYSA-N trifluoroacetic anhydride Chemical compound FC(F)(F)C(=O)OC(=O)C(F)(F)F QAEDZJGFFMLHHQ-UHFFFAOYSA-N 0.000 description 2
GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 2
DTVODKGBEXBXFW-BHIFYINESA-N (-)-3-methoxy butorphanol Chemical compound C([C@@]12C3=CC(OC)=CC=C3C[C@@]3([C@@]1(CCCC2)O)[H])CN3CC1CCC1 DTVODKGBEXBXFW-BHIFYINESA-N 0.000 description 1
NJQADTYRAYFBJN-FWWHASMVSA-N (1s,2s,4r)-2-bromo-4,7,7-trimethylbicyclo[2.2.1]heptan-3-one Chemical compound C1C[C@@]2(C)C(=O)[C@@H](Br)[C@@H]1C2(C)C NJQADTYRAYFBJN-FWWHASMVSA-N 0.000 description 1
SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 1
YBYCJQQRZPXLHU-UHFFFAOYSA-N 1,2,3,4,5,6,7,8-octahydroisoquinoline Chemical compound C1CNCC2=C1CCCC2 YBYCJQQRZPXLHU-UHFFFAOYSA-N 0.000 description 1
JYUXDXWXTPSAEL-UHFFFAOYSA-N 1,4-dioxane;oxolane Chemical compound C1CCOC1.C1COCCO1 JYUXDXWXTPSAEL-UHFFFAOYSA-N 0.000 description 1
ZQXCQTAELHSNAT-UHFFFAOYSA-N 1-chloro-3-nitro-5-(trifluoromethyl)benzene Chemical compound [O-][N+](=O)C1=CC(Cl)=CC(C(F)(F)F)=C1 ZQXCQTAELHSNAT-UHFFFAOYSA-N 0.000 description 1
XYPISWUKQGWYGX-UHFFFAOYSA-N 2,2,2-trifluoroethaneperoxoic acid Chemical compound OOC(=O)C(F)(F)F XYPISWUKQGWYGX-UHFFFAOYSA-N 0.000 description 1
ILNSWVUXAPSPEH-USXIJHARSA-N 3-methoxy-morphinan Chemical compound C1CCC[C@H]2[C@H]3CC4=CC=C(OC)C=C4[C@]21CCN3 ILNSWVUXAPSPEH-USXIJHARSA-N 0.000 description 1
LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 description 1
OKTJSMMVPCPJKN-NJFSPNSNSA-N Carbon-14 Chemical compound [14C] OKTJSMMVPCPJKN-NJFSPNSNSA-N 0.000 description 1
VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
206010013654 Drug abuse Diseases 0.000 description 1
CTZHXEOAVHVLCX-UHFFFAOYSA-N F.F.F.C1CCOC1 Chemical compound F.F.F.C1CCOC1 CTZHXEOAVHVLCX-UHFFFAOYSA-N 0.000 description 1
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
XADCESSVHJOZHK-UHFFFAOYSA-N Meperidine Chemical compound C=1C=CC=CC=1C1(C(=O)OCC)CCN(C)CC1 XADCESSVHJOZHK-UHFFFAOYSA-N 0.000 description 1
FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 1
JLTDJTHDQAWBAV-UHFFFAOYSA-N N,N-dimethylaniline Chemical compound CN(C)C1=CC=CC=C1 JLTDJTHDQAWBAV-UHFFFAOYSA-N 0.000 description 1
238000005481 NMR spectroscopy Methods 0.000 description 1
CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 1
239000008896 Opium Substances 0.000 description 1
LEHOTFFKMJEONL-UHFFFAOYSA-N Uric Acid Chemical compound N1C(=O)NC(=O)C2=C1NC(=O)N2 LEHOTFFKMJEONL-UHFFFAOYSA-N 0.000 description 1
239000000370 acceptor Substances 0.000 description 1
239000003377 acid catalyst Substances 0.000 description 1
238000005917 acylation reaction Methods 0.000 description 1
238000013019 agitation Methods 0.000 description 1
229930013930 alkaloid Natural products 0.000 description 1
150000003973 alkyl amines Chemical class 0.000 description 1
DTOSIQBPPRVQHS-PDBXOOCHSA-N alpha-linolenic acid Chemical compound CC\C=C/C\C=C/C\C=C/CCCCCCCC(O)=O DTOSIQBPPRVQHS-PDBXOOCHSA-N 0.000 description 1
235000020661 alpha-linolenic acid Nutrition 0.000 description 1
PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 1
125000003368 amide group Chemical group 0.000 description 1
238000004458 analytical method Methods 0.000 description 1
239000011260 aqueous acid Substances 0.000 description 1
UWTDFICHZKXYAC-UHFFFAOYSA-N boron;oxolane Chemical compound [B].C1CCOC1 UWTDFICHZKXYAC-UHFFFAOYSA-N 0.000 description 1
239000006227 byproduct Substances 0.000 description 1
229950005499 carbon tetrachloride Drugs 0.000 description 1
239000003610 charcoal Substances 0.000 description 1
239000002026 chloroform extract Substances 0.000 description 1
229960004126 codeine Drugs 0.000 description 1
238000004440 column chromatography Methods 0.000 description 1
LQNHRNOPWKZUSN-UHFFFAOYSA-N cyclobutylmethanamine Chemical compound NCC1CCC1 LQNHRNOPWKZUSN-UHFFFAOYSA-N 0.000 description 1
ZOOSILUVXHVRJE-UHFFFAOYSA-N cyclopropanecarbonyl chloride Chemical compound ClC(=O)C1CC1 ZOOSILUVXHVRJE-UHFFFAOYSA-N 0.000 description 1
125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 description 1
239000012067 demethylated product Substances 0.000 description 1
230000001419 dependent effect Effects 0.000 description 1
229960004132 diethyl ether Drugs 0.000 description 1
125000003438 dodecyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
229940079593 drug Drugs 0.000 description 1
239000003814 drug Substances 0.000 description 1
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
238000011156 evaluation Methods 0.000 description 1
238000001704 evaporation Methods 0.000 description 1
230000003203 everyday effect Effects 0.000 description 1
OROGSEYTTFOCAN-UHFFFAOYSA-N hydrocodone Natural products C1C(N(CCC234)C)C2C=CC(O)C3OC2=C4C1=CC=C2OC OROGSEYTTFOCAN-UHFFFAOYSA-N 0.000 description 1
229910052739 hydrogen Inorganic materials 0.000 description 1
239000001257 hydrogen Substances 0.000 description 1
230000003301 hydrolyzing effect Effects 0.000 description 1
238000002329 infrared spectrum Methods 0.000 description 1
125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
229960004488 linolenic acid Drugs 0.000 description 1
KQQKGWQCNNTQJW-UHFFFAOYSA-N linolenic acid Natural products CC=CCCC=CCC=CCCCCCCCC(O)=O KQQKGWQCNNTQJW-UHFFFAOYSA-N 0.000 description 1
238000004949 mass spectrometry Methods 0.000 description 1
NIQQIJXGUZVEBB-UHFFFAOYSA-N methanol;propan-2-one Chemical compound OC.CC(C)=O NIQQIJXGUZVEBB-UHFFFAOYSA-N 0.000 description 1
150000007522 mineralic acids Chemical class 0.000 description 1
238000002156 mixing Methods 0.000 description 1
229960005181 morphine Drugs 0.000 description 1
239000003887 narcotic antagonist Substances 0.000 description 1
239000002674 ointment Substances 0.000 description 1
ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid group Chemical group C(CCCCCCC\C=C/CCCCCCCC)(=O)O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 1
229960001027 opium Drugs 0.000 description 1
150000007524 organic acids Chemical class 0.000 description 1
235000005985 organic acids Nutrition 0.000 description 1
125000000466 oxiranyl group Chemical group 0.000 description 1
229910052760 oxygen Inorganic materials 0.000 description 1
229960000482 pethidine Drugs 0.000 description 1
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
238000000746 purification Methods 0.000 description 1
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
238000001953 recrystallisation Methods 0.000 description 1
239000012047 saturated solution Substances 0.000 description 1
125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
238000001228 spectrum Methods 0.000 description 1
208000011117 substance-related disease Diseases 0.000 description 1
150000003467 sulfuric acid derivatives Chemical class 0.000 description 1
239000000725 suspension Substances 0.000 description 1
150000003512 tertiary amines Chemical class 0.000 description 1
VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 1
239000012485 toluene extract Substances 0.000 description 1
239000012808 vapor phase Substances 0.000 description 1
239000008096 xylene Substances 0.000 description 1

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Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

CA339,989A 1976-03-23 1979-11-16 No translation available Expired CA1091675A (fr)

Priority Applications (1)

Application Number	Priority Date	Filing Date	Title
CA339,989A CA1091675A (fr)	1976-03-23	1979-11-16	No translation available

Applications Claiming Priority (6)

Application Number	Priority Date	Filing Date	Title
US669,795		1976-03-23
US05/669,795 US4058531A (en)	1976-03-23	1976-03-23	Process for the preparation of 14-hydroxymorphinan derivatives
US05/769,808 US4139534A (en)	1977-02-17	1977-02-17	Process for the preparation of 14-hydroxymorphinan derivatives
US769,808		1977-02-17
CA274,241A CA1086723A (fr)	1976-03-23	1977-03-18	Preparation de derives de la 14-hydroxymorphinane
CA339,989A CA1091675A (fr)	1976-03-23	1979-11-16	No translation available

Publications (1)

Publication Number	Publication Date
CA1091675A true CA1091675A (fr)	1980-12-16

Family

ID=27425979

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
CA339,989A Expired CA1091675A (fr)	1976-03-23	1979-11-16	No translation available

Country Status (1)

Country	Link
CA (1)	CA1091675A (fr)

1979
- 1979-11-16 CA CA339,989A patent/CA1091675A/fr not_active Expired

Legal Events

Date	Code	Title	Description
1997-12-16	MKEX	Expiry

Publication	Publication Date	Title
US4277605A (en)	1981-07-07	Chemical compounds
US4272540A (en)	1981-06-09	14-Methoxymorphinan-6-one compounds and therapeutic methods of treating pain and drug dependence with them
US4003903A (en)	1977-01-18	N-acyl-N-norsalutaridines and process for making them
US4001247A (en)	1977-01-04	1-ethyl 3a-(substituted-phenyl) decahydroisoquinoline
US4139534A (en)	1979-02-13	Process for the preparation of 14-hydroxymorphinan derivatives
Craig et al.	1948	Curariform Activity and Chemical Structure. II. Synthesis in the Benzyltetrahydroisoquinoline Series1
US4058531A (en)	1977-11-15	Process for the preparation of 14-hydroxymorphinan derivatives
US4115389A (en)	1978-09-19	Process of N-demethylating (-)-1-(p-methoxybenzyl)-2-methyl-1,2,3,4,5,6,7,8-octahydroisoquinoline
US3810899A (en)	1974-05-14	2-hydroxy-n-substituted-morphinan derivatives
US4194044A (en)	1980-03-18	Process for preparing 3-phenoxy morphinans
US4247697A (en)	1981-01-27	3-Phenoxy morphinans and their derivatives
US3914232A (en)	1975-10-21	2-And 4-acryloxy-N-substituted-morphinan derivatives
JPS5919096B2 (ja)	1984-05-02	ベンゾモルフィナン誘導体の製造法
CA1086723A (fr)	1980-09-30	Preparation de derives de la 14-hydroxymorphinane
US4029796A (en)	1977-06-14	Novel N-cycloalkylmethyl decahydroisoquinolines for producing opiate-like analgesia
JPS6047273B2 (ja)	1985-10-21	６，８−ジオキサモルフィナン化合物
US4163853A (en)	1979-08-07	1-(P-phenoxy)benzyl-1,2,3,4,5,6,7,8-octahydroisoquinolines
Sugasawa et al.	1958	Extension of Bischler-Napieralski reaction—I: Synthesis of isoquinoline derivatives: A synthesis of rac.-apomorphine dimethyl ether
CA1100496A (fr)	1981-05-05	Traduction non-disponible
US4302458A (en)	1981-11-24	Phthalidyl-isoquinoline derivatives
US4052389A (en)	1977-10-04	Derivatives of 9,10-dihydroxy-1-(p-alkoxybenzyl)-perhydroisoquinoline oxazine-3-one
US3796715A (en)	1974-03-12	8-alkoxy-3,4-dihydroisoquinolines
US4849420A (en)	1989-07-18	2,3,11,12-substituted-5,6,8,9,14,14a-hexahydroisoquino-[1,2-b][3]benzazepines
CA1040628A (fr)	1978-10-17	Derives de 4-benzazonine et mode de preparation
EP0039444A1 (fr)	1981-11-11	7,7-Ditosyloxyméthyl-4,5-alpha-époxy-morphinan-6-ols et leur application comme produits intermédiaires dans la production de dérivés époxymorphinanes