CA1092122A - Morphine/apomorphine rearrangement process - Google Patents
Morphine/apomorphine rearrangement processInfo
- Publication number
- CA1092122A CA1092122A CA291,508A CA291508A CA1092122A CA 1092122 A CA1092122 A CA 1092122A CA 291508 A CA291508 A CA 291508A CA 1092122 A CA1092122 A CA 1092122A
- Authority
- CA
- Canada
- Prior art keywords
- alkyl
- yield
- process according
- formula
- apomorphine
- Prior art date
- 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
Links
- 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 title claims abstract description 25
- 230000008707 rearrangement Effects 0.000 title claims abstract description 16
- VMWNQDUVQKEIOC-CYBMUJFWSA-N apomorphine Chemical compound C([C@H]1N(C)CC2)C3=CC=C(O)C(O)=C3C3=C1C2=CC=C3 VMWNQDUVQKEIOC-CYBMUJFWSA-N 0.000 title claims abstract description 11
- 229960004046 apomorphine Drugs 0.000 title claims description 15
- 238000000034 method Methods 0.000 title claims description 13
- 229960005181 morphine Drugs 0.000 title claims description 12
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 claims description 35
- 235000011007 phosphoric acid Nutrition 0.000 claims description 18
- 238000006243 chemical reaction Methods 0.000 claims description 15
- 238000010438 heat treatment Methods 0.000 claims description 7
- 229910052739 hydrogen Inorganic materials 0.000 claims description 7
- 239000001257 hydrogen Substances 0.000 claims description 7
- 150000001875 compounds Chemical class 0.000 claims 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 claims description 5
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 4
- OROGSEYTTFOCAN-UHFFFAOYSA-N hydrocodone Natural products C1C(N(CCC234)C)C2C=CC(O)C3OC2=C4C1=CC=C2OC OROGSEYTTFOCAN-UHFFFAOYSA-N 0.000 claims description 3
- BTGAJCKRXPNBFI-OAHLLOKOSA-N (8R)-7-propyl-5,6,6a,7-tetrahydro-4H-dibenzo[de,g]quinoline-13,14-diol Chemical compound C([C@H]1N(CCC)CC2)C3=CC=C(O)C(O)=C3C3=C1C2=CC=C3 BTGAJCKRXPNBFI-OAHLLOKOSA-N 0.000 claims description 2
- 229960004126 codeine Drugs 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims 1
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims 1
- 239000002253 acid Substances 0.000 abstract description 7
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 10
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 8
- 229960004838 phosphoric acid Drugs 0.000 description 8
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 7
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 7
- 239000000203 mixture Substances 0.000 description 6
- 229910052757 nitrogen Inorganic materials 0.000 description 5
- 239000007858 starting material Substances 0.000 description 5
- 125000004432 carbon atom Chemical group C* 0.000 description 4
- 230000000875 corresponding effect Effects 0.000 description 4
- 238000002844 melting Methods 0.000 description 4
- 230000008018 melting Effects 0.000 description 4
- DZUOQMBJJSBONO-CQSZACIVSA-N (6ar)-10-methoxy-6-methyl-5,6,6a,7-tetrahydro-4h-dibenzo[de,g]quinoline-11-ol Chemical compound CN1CCC2=CC=CC3=C2[C@H]1CC1=CC=C(OC)C(O)=C13 DZUOQMBJJSBONO-CQSZACIVSA-N 0.000 description 3
- MHPQCGZBAVXCGA-GFCCVEGCSA-N (6ar)-5,6,6a,7-tetrahydro-4h-dibenzo[de,g]quinoline-10,11-diol Chemical compound N1CCC2=CC=CC3=C2[C@H]1CC1=CC=C(O)C(O)=C13 MHPQCGZBAVXCGA-GFCCVEGCSA-N 0.000 description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 3
- 230000007062 hydrolysis Effects 0.000 description 3
- 238000006460 hydrolysis reaction Methods 0.000 description 3
- 239000011541 reaction mixture Substances 0.000 description 3
- -1 4-ethylcyclohexyl Chemical group 0.000 description 2
- 125000000217 alkyl group Chemical group 0.000 description 2
- OSGAYBCDTDRGGQ-UHFFFAOYSA-L calcium sulfate Chemical compound [Ca+2].[O-]S([O-])(=O)=O OSGAYBCDTDRGGQ-UHFFFAOYSA-L 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 150000002431 hydrogen Chemical class 0.000 description 2
- JMMWKPVZQRWMSS-UHFFFAOYSA-N isopropanol acetate Natural products CC(C)OC(C)=O JMMWKPVZQRWMSS-UHFFFAOYSA-N 0.000 description 2
- 229940011051 isopropyl acetate Drugs 0.000 description 2
- GWYFCOCPABKNJV-UHFFFAOYSA-N isovaleric acid Chemical compound CC(C)CC(O)=O GWYFCOCPABKNJV-UHFFFAOYSA-N 0.000 description 2
- 150000003014 phosphoric acid esters Chemical class 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 238000010561 standard procedure Methods 0.000 description 2
- JIAARYAFYJHUJI-UHFFFAOYSA-L zinc dichloride Chemical compound [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 0.000 description 2
- BXKJGGVENHTVBF-JFDOVZFRSA-N (4r,4ar,7s,7ar,12bs)-3-(2-phenylethyl)-2,4,4a,7,7a,13-hexahydro-1h-4,12-methanobenzofuro[3,2-e]isoquinoline-7,9-diol Chemical compound C([C@]12[C@H]3OC=4C(O)=CC=C(C2=4)C[C@@H]2[C@@H]1C=C[C@@H]3O)CN2CCC1=CC=CC=C1 BXKJGGVENHTVBF-JFDOVZFRSA-N 0.000 description 1
- 125000004974 2-butenyl group Chemical group C(C=CC)* 0.000 description 1
- 125000000069 2-butynyl group Chemical group [H]C([H])([H])C#CC([H])([H])* 0.000 description 1
- 125000001494 2-propynyl group Chemical group [H]C#CC([H])([H])* 0.000 description 1
- 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 1
- 241000859095 Bero Species 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
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-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
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 239000002269 analeptic agent Substances 0.000 description 1
- METKIMKYRPQLGS-UHFFFAOYSA-N atenolol Chemical compound CC(C)NCC(O)COC1=CC=C(CC(N)=O)C=C1 METKIMKYRPQLGS-UHFFFAOYSA-N 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 125000002837 carbocyclic group Chemical group 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 125000000753 cycloalkyl group Chemical group 0.000 description 1
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- LMKPHJYTFHAGHK-UHFFFAOYSA-N cyclodrine Chemical compound C1CCCC1(O)C(C(=O)OCCN(CC)CC)C1=CC=CC=C1 LMKPHJYTFHAGHK-UHFFFAOYSA-N 0.000 description 1
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
- 229960002069 diamorphine Drugs 0.000 description 1
- 239000003814 drug 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
- 125000001183 hydrocarbyl group Chemical group 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 230000036647 reaction Effects 0.000 description 1
- 229930195734 saturated hydrocarbon Natural products 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 230000002311 subsequent effect Effects 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000004809 thin layer chromatography Methods 0.000 description 1
- 238000010626 work up procedure Methods 0.000 description 1
- 235000005074 zinc chloride Nutrition 0.000 description 1
- 239000011592 zinc chloride Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D221/00—Heterocyclic compounds containing six-membered rings having one nitrogen atom as the only ring hetero atom, not provided for by groups C07D211/00 - C07D219/00
- C07D221/02—Heterocyclic compounds containing six-membered rings having one nitrogen atom as the only ring hetero atom, not provided for by groups C07D211/00 - C07D219/00 condensed with carbocyclic rings or ring systems
- C07D221/04—Ortho- or peri-condensed ring systems
- C07D221/18—Ring systems of four or more rings
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
- Other In-Based Heterocyclic Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US75788877A | 1977-01-10 | 1977-01-10 | |
| US757,888 | 1977-01-10 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA1092122A true CA1092122A (en) | 1980-12-23 |
Family
ID=25049636
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA291,508A Expired CA1092122A (en) | 1977-01-10 | 1977-11-22 | Morphine/apomorphine rearrangement process |
Country Status (14)
| Country | Link |
|---|---|
| JP (1) | JPS5387359A (en, 2012) |
| AU (1) | AU510976B2 (en, 2012) |
| BE (1) | BE862389A (en, 2012) |
| CA (1) | CA1092122A (en, 2012) |
| CH (1) | CH624674A5 (en, 2012) |
| DE (1) | DE2758954A1 (en, 2012) |
| DK (1) | DK584077A (en, 2012) |
| FR (1) | FR2376847A1 (en, 2012) |
| GB (1) | GB1566049A (en, 2012) |
| IE (1) | IE45922B1 (en, 2012) |
| LU (1) | LU78790A1 (en, 2012) |
| NL (1) | NL7714227A (en, 2012) |
| NZ (1) | NZ185799A (en, 2012) |
| SE (1) | SE7713456L (en, 2012) |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE3171561D1 (en) * | 1980-05-08 | 1985-09-05 | Univ Northeastern | N-substituted aporphines, a method of inducing emesis and a method of controlling psychosis utilising the same |
| WO1990012574A1 (en) * | 1989-04-25 | 1990-11-01 | Northeastern University | Dopamine agonist compounds |
| GB201915911D0 (en) * | 2019-11-01 | 2019-12-18 | Johnson Matthey Plc | Process |
-
1977
- 1977-11-22 GB GB4862177A patent/GB1566049A/en not_active Expired
- 1977-11-22 CA CA291,508A patent/CA1092122A/en not_active Expired
- 1977-11-23 IE IE237377A patent/IE45922B1/en unknown
- 1977-11-28 SE SE7713456A patent/SE7713456L/xx not_active Application Discontinuation
- 1977-11-28 NZ NZ18579977A patent/NZ185799A/xx unknown
- 1977-11-28 AU AU31013/77A patent/AU510976B2/en not_active Expired
- 1977-12-21 NL NL7714227A patent/NL7714227A/xx not_active Application Discontinuation
- 1977-12-28 FR FR7739473A patent/FR2376847A1/fr active Granted
- 1977-12-28 BE BE1008611A patent/BE862389A/xx unknown
- 1977-12-29 CH CH1622177A patent/CH624674A5/fr not_active IP Right Cessation
- 1977-12-29 JP JP15869177A patent/JPS5387359A/ja active Pending
- 1977-12-29 LU LU78790A patent/LU78790A1/xx unknown
- 1977-12-29 DK DK584077A patent/DK584077A/da unknown
- 1977-12-30 DE DE19772758954 patent/DE2758954A1/de not_active Withdrawn
Also Published As
| Publication number | Publication date |
|---|---|
| DK584077A (da) | 1978-07-11 |
| BE862389A (fr) | 1978-06-28 |
| AU510976B2 (en) | 1980-07-24 |
| FR2376847A1 (fr) | 1978-08-04 |
| LU78790A1 (en, 2012) | 1978-07-11 |
| NZ185799A (en) | 1979-12-11 |
| AU3101377A (en) | 1979-06-07 |
| SE7713456L (sv) | 1978-07-11 |
| FR2376847B1 (en, 2012) | 1980-08-22 |
| IE45922B1 (en) | 1982-12-29 |
| NL7714227A (nl) | 1978-07-12 |
| IE45922L (en) | 1978-07-10 |
| GB1566049A (en) | 1980-04-30 |
| CH624674A5 (en) | 1981-08-14 |
| JPS5387359A (en) | 1978-08-01 |
| DE2758954A1 (de) | 1978-07-13 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MKEX | Expiry |