DD235639A5 - Verfahren zum n-demethylieren von morphinan-alkaloiden - Google Patents

Verfahren zum n-demethylieren von morphinan-alkaloiden Download PDF

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Publication number: DD235639A5
Authority: DD; German Democratic Republic
Prior art keywords: group; hydrogen atom; carbon atoms; general formula; benzoyloxy
Prior art date: 1984-07-17

Application number

DD85278546A

Other languages

German (de)

English (en)

Inventor

Sandor Hosztafi

Tibor Timar

Julianna Nagy

Ilona Fabian

Original Assignee

��@��@��k��

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.)

1984-07-17

Filing date

1985-07-12

Publication date

1986-05-14

1985-07-12 Application filed by ��@��@��k�� filed Critical ��@��@��k��

1986-05-14 Publication of DD235639A5 publication Critical patent/DD235639A5/de

Links

238000000034 method Methods 0.000 title claims abstract description 19
238000010520 demethylation reaction Methods 0.000 title claims description 12
229930013053 morphinan alkaloid Natural products 0.000 title claims 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 title claims description 7
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims abstract description 34
HCUYBXPSSCRKRF-UHFFFAOYSA-N diphosgene Chemical compound ClC(=O)OC(Cl)(Cl)Cl HCUYBXPSSCRKRF-UHFFFAOYSA-N 0.000 claims abstract description 26
125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 24
YGYAWVDWMABLBF-UHFFFAOYSA-N Phosgene Chemical compound ClC(Cl)=O YGYAWVDWMABLBF-UHFFFAOYSA-N 0.000 claims abstract description 18
125000004432 carbon atom Chemical group C* 0.000 claims abstract description 18
125000004423 acyloxy group Chemical group 0.000 claims abstract description 15
238000006243 chemical reaction Methods 0.000 claims abstract description 15
125000001231 benzoyloxy group Chemical group C(C1=CC=CC=C1)(=O)O* 0.000 claims abstract description 14
125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 13
WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 claims abstract description 11
125000000217 alkyl group Chemical group 0.000 claims abstract description 11
150000001875 compounds Chemical class 0.000 claims abstract description 10
239000002253 acid Substances 0.000 claims abstract description 9
125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 claims abstract description 6
230000007062 hydrolysis Effects 0.000 claims abstract description 6
238000006460 hydrolysis reaction Methods 0.000 claims abstract description 6
125000005843 halogen group Chemical group 0.000 claims abstract description 5
238000002360 preparation method Methods 0.000 claims abstract description 5
125000002252 acyl group Chemical group 0.000 claims abstract description 4
125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims abstract description 4
229910052500 inorganic mineral Inorganic materials 0.000 claims abstract description 4
239000011707 mineral Substances 0.000 claims abstract description 4
125000003710 aryl alkyl group Chemical group 0.000 claims abstract description 3
125000003118 aryl group Chemical group 0.000 claims abstract description 3
125000004430 oxygen atom Chemical group O* 0.000 claims abstract description 3
229910000288 alkali metal carbonate Inorganic materials 0.000 claims abstract 4
150000008041 alkali metal carbonates Chemical class 0.000 claims abstract 4
229910052783 alkali metal Inorganic materials 0.000 claims abstract 3
239000002904 solvent Substances 0.000 claims abstract 3
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 24
BQJCRHHNABKAKU-KBQPJGBKSA-N morphine Chemical class 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 claims description 15
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 15
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims description 14
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 6
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 6
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 6
229910000029 sodium carbonate Inorganic materials 0.000 claims description 6
VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 claims description 4
235000010755 mineral Nutrition 0.000 claims description 3
239000001257 hydrogen Substances 0.000 claims description 2
229910052739 hydrogen Inorganic materials 0.000 claims description 2
125000001424 substituent group Chemical group 0.000 claims description 2
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical group CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims 3
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 claims 2
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims 2
150000001340 alkali metals Chemical class 0.000 claims 2
125000004185 ester group Chemical group 0.000 claims 2
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims 2
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims 1
150000007513 acids Chemical class 0.000 claims 1
239000003513 alkali Substances 0.000 claims 1
150000004945 aromatic hydrocarbons Chemical class 0.000 claims 1
239000011230 binding agent Substances 0.000 claims 1
239000003054 catalyst Substances 0.000 claims 1
125000003963 dichloro group Chemical group Cl* 0.000 claims 1
150000008282 halocarbons Chemical class 0.000 claims 1
150000002576 ketones Chemical class 0.000 claims 1
VNWKTOKETHGBQD-UHFFFAOYSA-N methane Natural products C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 claims 1
229910000028 potassium bicarbonate Inorganic materials 0.000 claims 1
235000015497 potassium bicarbonate Nutrition 0.000 claims 1
239000011736 potassium bicarbonate Substances 0.000 claims 1
229910000027 potassium carbonate Inorganic materials 0.000 claims 1
235000011181 potassium carbonates Nutrition 0.000 claims 1
TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 claims 1
229940086066 potassium hydrogencarbonate Drugs 0.000 claims 1
229910000030 sodium bicarbonate Inorganic materials 0.000 claims 1
235000017557 sodium bicarbonate Nutrition 0.000 claims 1
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims 1
-1 alkali metal hydrogen carbonates Chemical class 0.000 abstract description 7
238000002955 isolation Methods 0.000 abstract 1
150000003810 morphinanes Chemical class 0.000 abstract 1
235000011167 hydrochloric acid Nutrition 0.000 description 14
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 12
239000000243 solution Substances 0.000 description 11
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 10
238000003756 stirring Methods 0.000 description 8
CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 7
238000001816 cooling Methods 0.000 description 7
239000000047 product Substances 0.000 description 7
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
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 6
238000000605 extraction Methods 0.000 description 6
238000002844 melting Methods 0.000 description 6
230000008018 melting Effects 0.000 description 6
229960005181 morphine Drugs 0.000 description 6
VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 5
239000000908 ammonium hydroxide Substances 0.000 description 5
229910052757 nitrogen Inorganic materials 0.000 description 5
239000012074 organic phase Substances 0.000 description 5
150000003335 secondary amines Chemical class 0.000 description 5
150000003512 tertiary amines Chemical class 0.000 description 5
CKDWPUIZGOQOOM-UHFFFAOYSA-N Carbamyl chloride Chemical compound NC(Cl)=O CKDWPUIZGOQOOM-UHFFFAOYSA-N 0.000 description 4
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 4
HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 4
LLPOLZWFYMWNKH-CMKMFDCUSA-N hydrocodone Chemical compound C([C@H]1[C@H](N(CC[C@@]112)C)C3)CC(=O)[C@@H]1OC1=C2C3=CC=C1OC LLPOLZWFYMWNKH-CMKMFDCUSA-N 0.000 description 4
229960000240 hydrocodone Drugs 0.000 description 4
229910017053 inorganic salt Inorganic materials 0.000 description 4
239000000203 mixture Substances 0.000 description 4
231100000331 toxic Toxicity 0.000 description 4
230000002588 toxic effect Effects 0.000 description 4
150000003673 urethanes Chemical class 0.000 description 4
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
OGDVEMNWJVYAJL-LEPYJNQMSA-N Ethyl morphine Chemical compound C([C@H]1[C@H](N(CC[C@@]112)C)C3)=C[C@H](O)[C@@H]1OC1=C2C3=CC=C1OCC OGDVEMNWJVYAJL-LEPYJNQMSA-N 0.000 description 3
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
230000015572 biosynthetic process Effects 0.000 description 3
229960004126 codeine Drugs 0.000 description 3
ATDGTVJJHBUTRL-UHFFFAOYSA-N cyanogen bromide Chemical compound BrC#N ATDGTVJJHBUTRL-UHFFFAOYSA-N 0.000 description 3
PQLFROTZSIMBKR-UHFFFAOYSA-N ethenyl carbonochloridate Chemical compound ClC(=O)OC=C PQLFROTZSIMBKR-UHFFFAOYSA-N 0.000 description 3
OROGSEYTTFOCAN-UHFFFAOYSA-N hydrocodone Natural products C1C(N(CCC234)C)C2C=CC(O)C3OC2=C4C1=CC=C2OC OROGSEYTTFOCAN-UHFFFAOYSA-N 0.000 description 3
229910000042 hydrogen bromide Inorganic materials 0.000 description 3
239000012071 phase Substances 0.000 description 3
150000003839 salts Chemical class 0.000 description 3
MFXFQKMUCYHPFQ-BKRJIHRRSA-N 6-monoacetylcodeine Chemical compound C([C@H]1[C@H](N(CC[C@@]112)C)C3)=C[C@H](OC(C)=O)[C@@H]1OC1=C2C3=CC=C1OC MFXFQKMUCYHPFQ-BKRJIHRRSA-N 0.000 description 2
CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
JOYRKODLDBILNP-UHFFFAOYSA-N Ethyl urethane Chemical compound CCOC(N)=O JOYRKODLDBILNP-UHFFFAOYSA-N 0.000 description 2
QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 2
OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 2
XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 2
HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical class [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 2
QVIUKMVKLLVCDU-ATNYCFDYSA-N acetylmorphone Chemical compound O([C@H]1C(CC[C@H]23)=O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4OC(C)=O QVIUKMVKLLVCDU-ATNYCFDYSA-N 0.000 description 2
230000001476 alcoholic effect Effects 0.000 description 2
239000005557 antagonist Substances 0.000 description 2
238000009835 boiling Methods 0.000 description 2
239000003153 chemical reaction reagent Substances 0.000 description 2
AOGYCOYQMAVAFD-UHFFFAOYSA-N chlorocarbonic acid Chemical class OC(Cl)=O AOGYCOYQMAVAFD-UHFFFAOYSA-N 0.000 description 2
NEHMKBQYUWJMIP-UHFFFAOYSA-N chloromethane Chemical compound ClC NEHMKBQYUWJMIP-UHFFFAOYSA-N 0.000 description 2
150000001912 cyanamides Chemical class 0.000 description 2
RBOXVHNMENFORY-DNJOTXNNSA-N dihydrocodeine Chemical compound C([C@H]1[C@H](N(CC[C@@]112)C)C3)C[C@H](O)[C@@H]1OC1=C2C3=CC=C1OC RBOXVHNMENFORY-DNJOTXNNSA-N 0.000 description 2
230000000694 effects Effects 0.000 description 2
125000000623 heterocyclic group Chemical group 0.000 description 2
229910052943 magnesium sulfate Inorganic materials 0.000 description 2
235000019341 magnesium sulphate Nutrition 0.000 description 2
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 2
238000007086 side reaction Methods 0.000 description 2
239000000126 substance Substances 0.000 description 2
238000004809 thin layer chromatography Methods 0.000 description 2
GQXLVXJXRIWPET-UIHHKEIPSA-N (4R,4aR,7aR,12bS)-9-hydroxy-2,3,4,4a,7a,10,11,13-octahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinolin-7-one Chemical compound C1CC(O)=C2C=3[C@@]45[C@@H](O2)C(=O)C=C[C@H]4[C@@H](CC1=3)NCC5 GQXLVXJXRIWPET-UIHHKEIPSA-N 0.000 description 1
HVQUMOKQAJNIKK-ZTYRTETDSA-N (4r,4ar,7s,7ar,12bs)-1,2,3,4,4a,5,6,7,7a,13-decahydro-4,12-methanobenzofuro[3,2-e]isoquinoline-7,9-diol Chemical compound C([C@@H](NCC1)[C@@H]2CC[C@@H]3O)C4=CC=C(O)C5=C4[C@@]21[C@H]3O5 HVQUMOKQAJNIKK-ZTYRTETDSA-N 0.000 description 1
IKGNKASQBMZRJL-KOFBORESSA-N (4r,4ar,7s,7ar,12bs)-9-methoxy-1,2,3,4,4a,5,6,7,7a,13-decahydro-4,12-methanobenzofuro[3,2-e]isoquinoline-7-ol Chemical compound O[C@H]([C@@H]1O2)CC[C@H]3[C@H]4CC5=CC=C(OC)C2=C5[C@@]13CCN4 IKGNKASQBMZRJL-KOFBORESSA-N 0.000 description 1
YYCRAERBSFHMPL-XFKAJCMBSA-N (4r,4as,7ar,12bs)-4a-hydroxy-9-methoxy-3-methyl-2,4,7a,13-tetrahydro-1h-4,12-methanobenzofuro[3,2-e]isoquinoline-7-one Chemical compound O=C([C@@H]1O2)C=C[C@@]3(O)[C@]4([H])N(C)CC[C@]13C1=C2C(OC)=CC=C1C4 YYCRAERBSFHMPL-XFKAJCMBSA-N 0.000 description 1
ODIGIKRIUKFKHP-UHFFFAOYSA-N (n-propan-2-yloxycarbonylanilino) acetate Chemical compound CC(C)OC(=O)N(OC(C)=O)C1=CC=CC=C1 ODIGIKRIUKFKHP-UHFFFAOYSA-N 0.000 description 1
SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 1
SWWQQSDRUYSMAR-UHFFFAOYSA-N 1-[(4-hydroxyphenyl)methyl]-1,2,3,4-tetrahydroisoquinoline-6,7-diol;hydrochloride Chemical group Cl.C1=CC(O)=CC=C1CC1C2=CC(O)=C(O)C=C2CCN1 SWWQQSDRUYSMAR-UHFFFAOYSA-N 0.000 description 1
YYCRAERBSFHMPL-UHFFFAOYSA-N 14beta-Hydroxycodeinone Natural products O1C2C(=O)C=CC3(O)C4CC5=CC=C(OC)C1=C5C23CCN4C YYCRAERBSFHMPL-UHFFFAOYSA-N 0.000 description 1
ZSEMRXVWLGLSLX-PVHGPHFFSA-N C(C)(=O)O[C@@H]1[C@H]2[C@]34C=5C(=C(CCC5C[C@H]([C@@H]3C=C1)N(C)CC4)OCC)O2 Chemical compound C(C)(=O)O[C@@H]1[C@H]2[C@]34C=5C(=C(CCC5C[C@H]([C@@H]3C=C1)N(C)CC4)OCC)O2 ZSEMRXVWLGLSLX-PVHGPHFFSA-N 0.000 description 1
241000557626 Corvus corax Species 0.000 description 1
IJVCSMSMFSCRME-KBQPJGBKSA-N Dihydromorphine Chemical compound O([C@H]1[C@H](CC[C@H]23)O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4O IJVCSMSMFSCRME-KBQPJGBKSA-N 0.000 description 1
241000196324 Embryophyta Species 0.000 description 1
OGDVEMNWJVYAJL-UHFFFAOYSA-N Ethylmorphine Natural products C1C(N(CCC234)C)C2C=CC(O)C3OC2=C4C1=CC=C2OCC OGDVEMNWJVYAJL-UHFFFAOYSA-N 0.000 description 1
GVGLGOZIDCSQPN-PVHGPHFFSA-N Heroin Chemical compound O([C@H]1[C@H](C=C[C@H]23)OC(C)=O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4OC(C)=O GVGLGOZIDCSQPN-PVHGPHFFSA-N 0.000 description 1
238000005684 Liebig rearrangement reaction Methods 0.000 description 1
238000007126 N-alkylation reaction Methods 0.000 description 1
229910017974 NH40H Inorganic materials 0.000 description 1
ONBWJWYUHXVEJS-ZTYRTETDSA-N Normorphine Chemical compound C([C@@H](NCC1)[C@@H]2C=C[C@@H]3O)C4=CC=C(O)C5=C4[C@@]21[C@H]3O5 ONBWJWYUHXVEJS-ZTYRTETDSA-N 0.000 description 1
BRUQQQPBMZOVGD-XFKAJCMBSA-N Oxycodone Chemical compound O=C([C@@H]1O2)CC[C@@]3(O)[C@H]4CC5=CC=C(OC)C2=C5[C@@]13CCN4C BRUQQQPBMZOVGD-XFKAJCMBSA-N 0.000 description 1
UQCNKQCJZOAFTQ-ISWURRPUSA-N Oxymorphone Chemical compound O([C@H]1C(CC[C@]23O)=O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4O UQCNKQCJZOAFTQ-ISWURRPUSA-N 0.000 description 1
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
229920001807 Urea-formaldehyde Polymers 0.000 description 1
DLMBQCVWDSCRAH-PVHGPHFFSA-N [(4R,4aR,7S,7aR,12bS)-9-ethoxy-3-methyl-2,4,4a,7,7a,13-hexahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinolin-7-yl] acetate Chemical compound CC(=O)O[C@H]([C@@H]1O2)C=C[C@H]3[C@]4([H])N(C)CC[C@]13C1=C2C(OCC)=CC=C1C4 DLMBQCVWDSCRAH-PVHGPHFFSA-N 0.000 description 1
GMLSVPWCKDLNIC-SSTWWWIQSA-N [(4R,4aR,7S,7aR,12bS)-9-methoxy-1,2,3,4,4a,7,7a,13-octahydro-4,12-methanobenzofuro[3,2-e]isoquinolin-7-yl] acetate Chemical compound CC(=O)O[C@H]([C@@H]1O2)C=C[C@H]3[C@H]4CC5=CC=C(OC)C2=C5[C@@]13CCN4 GMLSVPWCKDLNIC-SSTWWWIQSA-N 0.000 description 1
238000005903 acid hydrolysis reaction Methods 0.000 description 1
230000002378 acidificating effect Effects 0.000 description 1
239000008186 active pharmaceutical agent Substances 0.000 description 1
239000013543 active substance Substances 0.000 description 1
230000010933 acylation Effects 0.000 description 1
238000005917 acylation reaction Methods 0.000 description 1
239000000556 agonist Substances 0.000 description 1
239000012670 alkaline solution Substances 0.000 description 1
230000003113 alkalizing effect Effects 0.000 description 1
229930013930 alkaloid Natural products 0.000 description 1
150000001412 amines Chemical class 0.000 description 1
KZOKOEQTKWBKOK-XHQKLZHNSA-N azidomorphine Chemical compound O([C@H]1[C@@H](CC[C@H]23)N=[N+]=[N-])C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4O KZOKOEQTKWBKOK-XHQKLZHNSA-N 0.000 description 1
GCBSCAKBRSMFCP-UHFFFAOYSA-N benzene;methanol Chemical compound OC.OC.C1=CC=CC=C1 GCBSCAKBRSMFCP-UHFFFAOYSA-N 0.000 description 1
239000012267 brine Substances 0.000 description 1
239000004202 carbamide Substances 0.000 description 1
239000001569 carbon dioxide Substances 0.000 description 1
229910002092 carbon dioxide Inorganic materials 0.000 description 1
239000003518 caustics Substances 0.000 description 1
238000005660 chlorination reaction Methods 0.000 description 1
WGXZDYPGLJYBJW-UHFFFAOYSA-N chloroform;propan-2-ol Chemical compound CC(C)O.ClC(Cl)Cl WGXZDYPGLJYBJW-UHFFFAOYSA-N 0.000 description 1
238000003776 cleavage reaction Methods 0.000 description 1
239000013078 crystal Substances 0.000 description 1
230000006196 deacetylation Effects 0.000 description 1
238000003381 deacetylation reaction Methods 0.000 description 1
238000000354 decomposition reaction Methods 0.000 description 1
239000012649 demethylating agent Substances 0.000 description 1
NCXVKLDKUADJPV-PVHGPHFFSA-N diacetyldihydromorphine Chemical compound O([C@H]1[C@H](CC[C@H]23)OC(C)=O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4OC(C)=O NCXVKLDKUADJPV-PVHGPHFFSA-N 0.000 description 1
238000004821 distillation Methods 0.000 description 1
229940079593 drug Drugs 0.000 description 1
239000003814 drug Substances 0.000 description 1
238000001035 drying Methods 0.000 description 1
239000003480 eluent Substances 0.000 description 1
150000002148 esters Chemical class 0.000 description 1
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
HNPDNOZNULJJDL-UHFFFAOYSA-N ethyl n-ethenylcarbamate Chemical class CCOC(=O)NC=C HNPDNOZNULJJDL-UHFFFAOYSA-N 0.000 description 1
229960004578 ethylmorphine Drugs 0.000 description 1
125000000524 functional group Chemical group 0.000 description 1
229910052736 halogen Inorganic materials 0.000 description 1
150000002367 halogens Chemical class 0.000 description 1
230000003301 hydrolyzing effect Effects 0.000 description 1
WVLOADHCBXTIJK-YNHQPCIGSA-N hydromorphone Chemical compound O([C@H]1C(CC[C@H]23)=O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4O WVLOADHCBXTIJK-YNHQPCIGSA-N 0.000 description 1
229960001410 hydromorphone Drugs 0.000 description 1
239000005457 ice water Substances 0.000 description 1
231100001231 less toxic Toxicity 0.000 description 1
238000004519 manufacturing process Methods 0.000 description 1
238000001819 mass spectrum Methods 0.000 description 1
229940050176 methyl chloride Drugs 0.000 description 1
XMJHPCRAQCTCFT-UHFFFAOYSA-N methyl chloroformate Chemical compound COC(Cl)=O XMJHPCRAQCTCFT-UHFFFAOYSA-N 0.000 description 1
230000005012 migration Effects 0.000 description 1
238000013508 migration Methods 0.000 description 1
239000003887 narcotic antagonist Substances 0.000 description 1
HKOIXWVRNLGFOR-KOFBORESSA-N norcodeine Chemical compound O[C@H]([C@@H]1O2)C=C[C@H]3[C@H]4CC5=CC=C(OC)C2=C5[C@@]13CCN4 HKOIXWVRNLGFOR-KOFBORESSA-N 0.000 description 1
229940051807 opiod analgesics morphinan derivative Drugs 0.000 description 1
229960005118 oxymorphone Drugs 0.000 description 1
230000000144 pharmacologic effect Effects 0.000 description 1
ISWSIDIOOBJBQZ-UHFFFAOYSA-N phenol group Chemical group C1(=CC=CC=C1)O ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 1
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
239000002244 precipitate Substances 0.000 description 1
238000010926 purge Methods 0.000 description 1
238000000746 purification Methods 0.000 description 1
238000000197 pyrolysis Methods 0.000 description 1
230000009257 reactivity Effects 0.000 description 1
230000007017 scission Effects 0.000 description 1
238000000926 separation method Methods 0.000 description 1
239000010865 sewage Substances 0.000 description 1
239000000741 silica gel Substances 0.000 description 1
229910002027 silica gel Inorganic materials 0.000 description 1
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
239000007858 starting material Substances 0.000 description 1
239000000725 suspension Substances 0.000 description 1
230000001225 therapeutic effect Effects 0.000 description 1
XLRPYZSEQKXZAA-OCAPTIKFSA-N tropane Chemical group C1CC[C@H]2CC[C@@H]1N2C XLRPYZSEQKXZAA-OCAPTIKFSA-N 0.000 description 1
229930004668 tropane alkaloid Natural products 0.000 description 1
150000003813 tropane derivatives Chemical class 0.000 description 1
238000007738 vacuum evaporation Methods 0.000 description 1
231100000925 very toxic Toxicity 0.000 description 1
125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
239000011701 zinc Substances 0.000 description 1
229910052725 zinc Inorganic materials 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D489/00—Heterocyclic compounds containing 4aH-8, 9 c- Iminoethano-phenanthro [4, 5-b, c, d] furan ring systems, e.g. derivatives of [4, 5-epoxy]-morphinan of the formula:
- C07D489/02—Heterocyclic compounds containing 4aH-8, 9 c- Iminoethano-phenanthro [4, 5-b, c, d] furan ring systems, e.g. derivatives of [4, 5-epoxy]-morphinan of the formula: with oxygen atoms attached in positions 3 and 6, e.g. morphine, morphinone
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D489/00—Heterocyclic compounds containing 4aH-8, 9 c- Iminoethano-phenanthro [4, 5-b, c, d] furan ring systems, e.g. derivatives of [4, 5-epoxy]-morphinan of the formula:
- C07D489/06—Heterocyclic compounds containing 4aH-8, 9 c- Iminoethano-phenanthro [4, 5-b, c, d] furan ring systems, e.g. derivatives of [4, 5-epoxy]-morphinan of the formula: with a hetero atom directly attached in position 14
- C07D489/08—Oxygen atom

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Preparation Of Compounds By Using Micro-Organisms (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)
Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Ultra Sonic Daignosis Equipment (AREA)
Measurement And Recording Of Electrical Phenomena And Electrical Characteristics Of The Living Body (AREA)
Other In-Based Heterocyclic Compounds (AREA)
Cephalosporin Compounds (AREA)
Finger-Pressure Massage (AREA)
Other Investigation Or Analysis Of Materials By Electrical Means (AREA)
Polysaccharides And Polysaccharide Derivatives (AREA)
Polyesters Or Polycarbonates (AREA)
Materials For Photolithography (AREA)
Electrophonic Musical Instruments (AREA)
Stringed Musical Instruments (AREA)

DD85278546A 1984-07-17 1985-07-12 Verfahren zum n-demethylieren von morphinan-alkaloiden DD235639A5 (de)

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
HU842774A HU197750B (en)	1984-07-17	1984-07-17	Process for n-demethylation of morphine alkaloids

Publications (1)

Publication Number	Publication Date
DD235639A5 true DD235639A5 (de)	1986-05-14

Family

ID=10961043

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
DD85278546A DD235639A5 (de)	1984-07-17	1985-07-12	Verfahren zum n-demethylieren von morphinan-alkaloiden

Country Status (18)

Country	Link
EP (1)	EP0168686B1 (cs)
JP (1)	JPS6193184A (cs)
AT (1)	ATE41933T1 (cs)
BG (1)	BG44029A3 (cs)
CS (1)	CS251792B2 (cs)
DD (1)	DD235639A5 (cs)
DE (1)	DE3569244D1 (cs)
DK (1)	DK322385A (cs)
ES (1)	ES8603716A1 (cs)
FI (1)	FI81583C (cs)
HU (1)	HU197750B (cs)
IL (2)	IL75509A0 (cs)
IN (1)	IN166255B (cs)
NO (1)	NO161915C (cs)
PL (1)	PL254552A1 (cs)
RO (1)	RO91516B (cs)
SU (1)	SU1398776A3 (cs)
YU (1)	YU45264B (cs)

Families Citing this family (5)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
CA2709862C (en) *	2007-12-17	2016-03-15	Peter X. Wang	Sinomenine derivatives and processes for their synthesis
JP5688974B2 (ja) *	2007-12-17	2015-03-25	マリンクロッドエルエルシー	（＋）−オピエートの生成のためのプロセスおよび化合物
DE112010001980T8 (de) *	2009-05-12	2012-11-08	Board Of Regents, The University Of Texas System	Synthese von Morphin und verwandten Derivaten
WO2012008984A1 (en) *	2010-07-16	2012-01-19	Mallinckrodt Llc	(+)-morphinans as antagonists of toll-like receptor 9 and therapeutic uses thereof
KR20140063763A (ko)	2011-09-08	2014-05-27	말린크로트 엘엘씨	중간체를 단리하지 않는 알칼로이드의 제조 방법

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
SE367407B (cs) *	1967-08-04	1974-05-27	Boehringer Sohn Ingelheim
DE2254298A1 (de) *	1972-11-06	1974-05-16	Boehringer Sohn Ingelheim	Neue (heteroarylmethyl)-normorphine, deren saeureadditionssalze, verfahren zu deren herstellung sowie deren verwendung als arzneimittel
DE2727805A1 (de) *	1977-06-21	1979-01-04	Goedecke Ag	Verfahren zur herstellung von oxynormorphon

1984
- 1984-07-17 HU HU842774A patent/HU197750B/hu not_active IP Right Cessation
1985
- 1985-06-13 IL IL75509A patent/IL75509A0/xx not_active IP Right Cessation
- 1985-06-14 IN IN476/DEL/85A patent/IN166255B/en unknown
- 1985-06-20 ES ES544385A patent/ES8603716A1/es not_active Expired
- 1985-06-26 EP EP85107895A patent/EP0168686B1/de not_active Expired
- 1985-06-26 DE DE8585107895T patent/DE3569244D1/de not_active Expired
- 1985-06-26 AT AT85107895T patent/ATE41933T1/de not_active IP Right Cessation
- 1985-07-12 DD DD85278546A patent/DD235639A5/de not_active IP Right Cessation
- 1985-07-15 FI FI852779A patent/FI81583C/fi not_active IP Right Cessation
- 1985-07-15 RO RO119568A patent/RO91516B/ro unknown
- 1985-07-15 PL PL25455285A patent/PL254552A1/xx unknown
- 1985-07-15 DK DK322385A patent/DK322385A/da not_active Application Discontinuation
- 1985-07-15 BG BG071084A patent/BG44029A3/xx unknown
- 1985-07-16 SU SU853923700A patent/SU1398776A3/ru active
- 1985-07-16 CS CS855280A patent/CS251792B2/cs unknown
- 1985-07-16 JP JP60156846A patent/JPS6193184A/ja active Pending
- 1985-07-16 NO NO852838A patent/NO161915C/no unknown
- 1985-07-17 YU YU1174/85A patent/YU45264B/xx unknown
1986
- 1986-04-15 IL IL78503A patent/IL78503A/xx not_active IP Right Cessation

Also Published As

Publication number	Publication date
NO161915B (no)	1989-07-03
EP0168686B1 (de)	1989-04-05
DK322385D0 (da)	1985-07-15
FI852779L (fi)	1986-01-18
FI852779A0 (fi)	1985-07-15
YU45264B (en)	1992-05-28
FI81583B (fi)	1990-07-31
JPS6193184A (ja)	1986-05-12
PL254552A1 (en)	1986-07-15
NO161915C (no)	1989-10-11
BG44029A3 (en)	1988-09-15
CS251792B2 (en)	1987-08-13
HU197750B (en)	1989-05-29
SU1398776A3 (ru)	1988-06-15
HUT38645A (en)	1986-06-30
IL75509A0 (en)	1985-10-31
EP0168686A1 (de)	1986-01-22
DE3569244D1 (en)	1989-05-11
DK322385A (da)	1986-01-18
NO852838L (no)	1986-01-20
YU117485A (en)	1988-04-30
FI81583C (fi)	1990-11-12
RO91516A (ro)	1987-06-30
IN166255B (cs)	1990-03-31
ES544385A0 (es)	1986-01-16
ATE41933T1 (de)	1989-04-15
CS528085A2 (en)	1986-12-18
RO91516B (ro)	1987-07-01
IL78503A (en)	1990-01-18
ES8603716A1 (es)	1986-01-16

Legal Events

Date	Code	Title	Description
1999-02-04	ENJ	Ceased due to non-payment of renewal fee

Publication	Publication Date	Title
EP1554282B1 (de)	2008-05-28	Morphinanderivate substituiert in position 14 und deren quartäre ammoniumsalze, herstellungsverfahren und verwendung
DE2633600A1 (de)	1977-02-17	Verfahren zur desoxydation von sekundaeren alkoholen
DE2330912C3 (de)	1979-01-11	Verfahren zur Herstellung von Bromergolinverbindungen
EP1808435B1 (de)	2011-10-05	Technische Herstellung von Tiotropiumbromid
EP0168686B1 (de)	1989-04-05	Verfahren zum N-demethylieren von Morphinan-alkaloiden
DE2727805A1 (de)	1979-01-04	Verfahren zur herstellung von oxynormorphon
DD264696A5 (de)	1989-02-08	Verfahren zur herstellung von neuen imidazolderivaten
DE3546218C2 (cs)	1993-07-22
DE69912264T2 (de)	2004-07-22	Verfahren zur herstellung chiraler (s)-2,3-disubstituierter 1-propylamin-derivate
SU856381A3 (ru)	1981-08-15	Способ получени производных морфина
DE69937988T2 (de)	2008-12-24	Verfahren zur herstellung von 3-cephemderivaten
DE4117507A1 (de)	1992-11-26	Verfahren zur herstellung von n(pfeil hoch)6(pfeil hoch)-substituierten lysin-derivaten
DE69603419T3 (de)	2006-06-29	Verfahren zur Herstellung von optisch aktiven Amiden
DE2559976C2 (cs)	1991-12-19
AT401058B (de)	1996-06-25	Verfahren zum herstellen von derivaten des 4a,5, 9,10,11,12,-hexahydro-6h-benzofuro(3a,-3,2-ef) (2)benzazepins
DE69918681T2 (de)	2005-07-21	Verfahren zur herstellung von beta-hydroxyestern
CH634573A5 (de)	1983-02-15	Verfahren zur herstellung von neuen 14-substituierten vincanderivaten.
DE112010005112T5 (de)	2012-12-06	Verfahren zur Herstellung von Nortropylbenzilat und dessen Salzen sowie dabei verwendeten Zwischenprodukten
He et al.	1991	N‐demethylation of (±)‐6β‐acetoxy‐3‐tropinone. Synthesis of (±)‐6β‐acetoxynortropane
Kim	1977	N-Demethylation of Apomorphine using Methyl Chloroformate
DE68917994T2 (de)	1995-05-04	Verfahren zur Herstellung von Pyrrolizinderivaten.
DE2558158A1 (de)	1976-07-01	Neues verfahren zur herstellung von threo-threonin
DE68903133T2 (de)	1993-04-29	Pyrrolizinderivat und seine herstellung.
GB2036022A (en)	1980-06-25	Hexahydro-2,6-mthano-3-benzazocines and preparation thereof
DE1288589B (de)	1969-02-06	N-(2-Chlor-5-trifluormethylphenyl)-N'-methylharnstoff und Verfahren zu dessen Herstellung