CA1212108A - Process for the preparation of oripavine derivative - Google Patents
Process for the preparation of oripavine derivativeInfo
- Publication number
- CA1212108A CA1212108A CA000442036A CA442036A CA1212108A CA 1212108 A CA1212108 A CA 1212108A CA 000442036 A CA000442036 A CA 000442036A CA 442036 A CA442036 A CA 442036A CA 1212108 A CA1212108 A CA 1212108A
- Authority
- CA
- Canada
- Prior art keywords
- endoethano
- methyl
- hydroxy
- give
- butyl
- 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
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- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
ABSTRACT OF THE DISCLOSURE
A process for the preparation of the compound N-cyclopropylmethyl-6,14-endoethano-7-(2-hydroxy-2-methyl-2-ter-butyl)-tetrahydronororipavine which comprises reacting thebaine with acrolein to undergo Diels-Alder reaction to give 6,14-endoethano-7-formyl-tetrahydrothe-baine. This is reacted with methyl magnesium iodide to give 6,14-endoethano-7-(2-hydroxy-2-methyl)-tetrahydrothebaine which is oxidized by reaction with potassium permanganate to give 6,14-endoethano-7-acetyl-tetrahydrothebaine which is hydrogenated using palladium catalyst to give 6,14-endoethano-7-acetyltetrahydrothebaine. Reaction with ter-butyl magnesium chloride gives 6,14-endoethano-7-(2-hydroxy-2-methyl-2-ter-butyl)-tetxahydrothebaine which is reacted with cyanogen bromide to give N-cyano-6,14-endoethano-7-(2-hydroxy-2-methyl-2-ter-butyl) tetrahydro-thebaine which is reacted with cyanoyen bromide to give N-cyano-6,14-endoethano-7-(2-hydroxy-2-methyl-2-terbutyl)-tetrahydrothebaine which is demethylated by treatment with potassium hydroxide in one pot at 210°C to give 6,14-endoethano-7-(2-hydroxy-2-methyl-2-ter-butyl)-tetra-hydronororipavine which on treatment with cyclo-propyl methyl bromide gives the compound N-cyclo-propylmethyl-6,14-endoethano-7-(2-hydroxy-2-methyl-2-ter-butyl)-tetra-hydronororipavine. The process proceeds smoothly with readily available reactants, and yields a pure product, advantages over the prior art.
A process for the preparation of the compound N-cyclopropylmethyl-6,14-endoethano-7-(2-hydroxy-2-methyl-2-ter-butyl)-tetrahydronororipavine which comprises reacting thebaine with acrolein to undergo Diels-Alder reaction to give 6,14-endoethano-7-formyl-tetrahydrothe-baine. This is reacted with methyl magnesium iodide to give 6,14-endoethano-7-(2-hydroxy-2-methyl)-tetrahydrothebaine which is oxidized by reaction with potassium permanganate to give 6,14-endoethano-7-acetyl-tetrahydrothebaine which is hydrogenated using palladium catalyst to give 6,14-endoethano-7-acetyltetrahydrothebaine. Reaction with ter-butyl magnesium chloride gives 6,14-endoethano-7-(2-hydroxy-2-methyl-2-ter-butyl)-tetxahydrothebaine which is reacted with cyanogen bromide to give N-cyano-6,14-endoethano-7-(2-hydroxy-2-methyl-2-ter-butyl) tetrahydro-thebaine which is reacted with cyanoyen bromide to give N-cyano-6,14-endoethano-7-(2-hydroxy-2-methyl-2-terbutyl)-tetrahydrothebaine which is demethylated by treatment with potassium hydroxide in one pot at 210°C to give 6,14-endoethano-7-(2-hydroxy-2-methyl-2-ter-butyl)-tetra-hydronororipavine which on treatment with cyclo-propyl methyl bromide gives the compound N-cyclo-propylmethyl-6,14-endoethano-7-(2-hydroxy-2-methyl-2-ter-butyl)-tetra-hydronororipavine. The process proceeds smoothly with readily available reactants, and yields a pure product, advantages over the prior art.
Description
`` 12~
This invention relates to a novel process for the synthesis of the compound N~cyclopropylmethyl-6,14-endoethano-7-(2-hydroxy-2-methyl-2-terbutyl)-tetraAudrey-nororipavine from theba.ine.
It it known to synthesize the compound N-cyclo-propyl-methyl-6,14-endoethano-7-(2-hydroxy-2-methyyl-2-ter-butyl)-tetrahydronororipavine from thebaine. The conventional scheme, as shown below, consists in the following steps: treating thebaine formula I with methylvinylketone to give 6,14-endoethano-7-acetyltetra-hydrothebaine (formula I hydrogenation using palladium catalyst to give 6,14-endoethano-7-acetyltetrahydro-thebaine (formula 3); reaction with ter-butyl magnesium chloride to give 6,14-endoethano-7-(2-hydroxy-2-methyl-2-ter-butyl)-tetrahydrothebaine Formula I reaction with cyanogen bromide to give N-cyano-6,14-endoethano-7-(2-hydroxy-20methyl-2-ter-butyl)-tetrahydrothebaine (formula 5) ; reaction with potassium hydroxide at 170C to give 6,14endoethano-7-(2-hydroxy-2-methyl-2-terbutyl)-tetraa-TV hydronorthebaine formula 6); reaction with cyclopropyl carbonyl chloride followed by reduction with lithium alum-Nemo hydrides to give N-cyclopropylmethyl-6,14 endoethano-7-(2-hydroxy-2-methyl-2-ter-butyl)-tetrahydronorthebbrine (formula 7); reaction with potassium hydroxide at 210C to give N-cyclopropylmethyl-6,14-endoethano-7 (2-hydroxy-2-methyl-2-ter-butyl)-tetrahydronororipavine (formula 8).
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~2~Z~ 0~3 The drawbacks of the conventional process are first the methyl vinyl kitten required for preparing the-brine adduce it not always easily available. Secondly the thebaine adduce obtained through acrolein gives a purer product as compared to methyl vinyl kitten. Further the reduction of Pd/C proceeds quite smoothly for the thebaine adduce synthesized from acrolein.
This invention provides a novel simplified pro-cuss for the preparation of the compound N-cyclopropyl-methyl-6,14-endoethano-7-(2-hydroxy-2-methyl-2-terr-butyl)-tetrahydronororipavine, which overcomes the drawbacks ox the conventional process.
Accordingly the present invention is a process for the preparation of the compound N-cyclopropylmethyl-6, 14-endothano-7-(2-hydroxy-2-methyl-2-ter-butyl)-teetrahydro-nororipavine that comprises reacting thebaine with acrolein to undergo Diels-Alder reaction to give 6,14-endoethano-7-formyl-tetrahydrothebaine which is reacted with methyl magnesium iodide to give 6,14-endoethano-7-(2-hydroxy-2-methyl)-tetrahydrothebaine which is oxidized by reaction with potassium permanganate to give 6,14-endoethano-7-acetyl-tetrahydrothebaine which is hydrogenated using palladium catalyst to give 6,14-endoethano-7-acetyletra-hydrothebaine which is reacted with ter-butyl magnesium chloride to give 6,14-endoethano-7-(2-hydroxy-2-methyl-2-ter-butyl-tetrahydrothebaine which is reacted with cyanogen -"` lo Ox bromide to give N-cyano-6,14-endoethano-7-t2-hydroxy-2-methyl-1-2-ter-butyl)-tetrahydrothebaine which is dime thy-fated by treatment with potassium hydroxide in one pot 210C to give 6,14-endoethano-7-(2-hydroxy-2 methyl-2-terbutyl)-te~rahydronororipavine which on treatment with cyclopropyl methyl bromide gives the compound N-cyclopro-pylmethyl-6,14-endoethano-7-(2-hydroxy-2--methyl-2Tory-butyl)-tetrahydronororipavine.
The process of preparing the compound N-cyclo propylmethyl-6,14-endoethano-7-(2-hydroxy-2-methylliter butyl)-tetra-hydronororipavine according to the present invention may be shown as:
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The compound prepared according to this invention is therapeutically useful because of its power to effect the CONS, particularly through analgesic, sedative and anti-tussive effects and to antagonize the effect of narcotic drugs. The compound is marketed as a drug under the trade mark "Buprenorphine".
The following examples illustrate the preparation of the compound N-cyclopropylmethyl-6,14-endoethano-7-(2-hydroxy-2-met:hyl~2-texbutyl~-tetrahydxonororipaviire according to the present invention.
6,14-endoethano-7-formyl-tetrahydrothebaine (Formula 12) A mixture of thebaine (formula 11~ (6 g) and acrolein (20 ml) in Bunyan (25 ml) was reflexed over water bath for 12 hours. the solvent an unrequited acrolein were removed by distillation. The solid obtained was washed repeatedly with hexane. The adduce was separated from thebaine by recrystallization from the ethanol. Thebaine-acrolein adduce was obtained as a colorless crystalline solid mop.
109, 6 gm(85%)M:367; M+ 367.
-` LO Ox EXAMPLE _ 6/14-endoethano 7~(2-hydroxy-2-methyl)-tetrahydrothebaine (Formula 13) A solution of methyl magnesium iodide was prepared from magnesium (38.1 gym) in ether (300 ml) and methyliodie (1.94 gym) in ether (200 ml) and Bunsen (20 ml). The mix-lure was stirred for 2 hours, 6,14-endoethano-7-formyl-tetrahydrothebaine (100 gym) in Bunsen (500 ml) was added over 1 hour to the stirred mixture. After standing over-night the mixture was added to a saturated aqueous solution of ammonium chloride (5 lit.). The organic layer was separated and the aqueous layer was further extracted with ether. The solvent was removed to give 40 g of the desired product. Simple recrystallization from methanol gives a product having mop. 140Q, M:398.47; M+ 398.5.
6,14-endoethano-7-acetyl tetrahydrothebaine (Formula 14) 6,14-endoethano-7-acetyl tetrahydrothebaine (10 gym) was dissolved in 160 ml, acetone. Portions under stirring at room temperature potassium permanganate ~7.93 gym) was added. The next quantity was added only when the earlier quantity was utilized. Stirring was continued for 6 hours, after addition of potassium permanganate was over. The reaction mixture was filtered off Noah, washed well with hot acetone. The solvent was removed on water bath to 1;~3L2~0~
yield (9 gym) (95~) of the desired product mop 120, My 381.47; M+ 381.5.
6,14-endoethano-7-acetyltetrahydrothebaine Formula 15) 6,14-endoethano-7-acetyl tetrahydrothebaine (25 gym) is ethanol (500 ml) was stirred with 10% Pd/c l2.5 g) under hydrogen at 85 pi and 90C for 10-12 hours. The soul-lion was filtered from the catalyst and evaporated. The residue was recrystallized from methanol to give the required product (20 gym) mop. 134C~ M:383; My 383.
6/14-endoethano-7-(2-hydroxy~2-methyl-2-terbutyl)--twitter-hydrothebaine (Formula 16) 100 gym of 6,14-endoethano-7-acetyltetrahydrothebaine dissolved in 500 ml of Bunsen is added drops to a soul-lion of ter-butyl magnesium chloride from 85 g of magnet slum, 275 g of t-butylchloride in 1 lithe of dry ether.
The reaction mixture is stirred at room temperature for 8 hours and then decomposed under cooling with saturated ammonium chloride solution. The ether layer is separated dried over McCoy and evaporated to yield a residue 16 gym of 6,14-endoethano-7-(2-hydroxy-2-methyl-2-terbutyl) twitter-hydrothebaine, mop. 180-189~C.
N-cyano~6,14-endoethano-7-~2-hydroxy-2-methyl-2-teerbutyl)-tetrahydrothebaine (Formula 17) The Grignard product (formula lug) obtained from Example 5 (50 gym) is dissolved in 250 ml of chloroform. Cyanogen bromide (30 gym) is added and the mixture is reflexed for 8 hours. The chloroform was evaporated and the residue was recrystallized from -ethics ethanol, when the N-cyano-nor compound (38 gym) was obtained with mop. 205C.
6,14-endoethano-7-(2-hydroxy-2-methyl-2-ter-butyl~~ twitter-_ _ hydronororipavine (Formula 18 The Grignard product (formula 16) obtained from Example 5 (50 gym) is dissolved in 250 ml of chloroform. Cyanogen bromide (30 gym) is added and the mixture is reflexed for 8 hours. The chloroform was evaporated and the residue was recrystallized from -ethics ethanol, when the N-cyano-nor compound ~38 gym) was obtained with mop. 205C, was added to a vigorously stirred mixture of 30 gym of potassium hydroxide in 300 ml, of diethylene glycol at 170C. The reaction mixture is maintained at 170C. for 8 hours. The reaction mixture is decomposed with ten times, its volume by ice cold water. The precipitated solid is filtered, washed with water and dried. The northebaine 12 gym is obtained with mop. 162-169C.
~231 I
N-cycloProp~lmethyl-6,l4-endoethano-7-(2 hydroxY-2-methy~=
This invention relates to a novel process for the synthesis of the compound N~cyclopropylmethyl-6,14-endoethano-7-(2-hydroxy-2-methyl-2-terbutyl)-tetraAudrey-nororipavine from theba.ine.
It it known to synthesize the compound N-cyclo-propyl-methyl-6,14-endoethano-7-(2-hydroxy-2-methyyl-2-ter-butyl)-tetrahydronororipavine from thebaine. The conventional scheme, as shown below, consists in the following steps: treating thebaine formula I with methylvinylketone to give 6,14-endoethano-7-acetyltetra-hydrothebaine (formula I hydrogenation using palladium catalyst to give 6,14-endoethano-7-acetyltetrahydro-thebaine (formula 3); reaction with ter-butyl magnesium chloride to give 6,14-endoethano-7-(2-hydroxy-2-methyl-2-ter-butyl)-tetrahydrothebaine Formula I reaction with cyanogen bromide to give N-cyano-6,14-endoethano-7-(2-hydroxy-20methyl-2-ter-butyl)-tetrahydrothebaine (formula 5) ; reaction with potassium hydroxide at 170C to give 6,14endoethano-7-(2-hydroxy-2-methyl-2-terbutyl)-tetraa-TV hydronorthebaine formula 6); reaction with cyclopropyl carbonyl chloride followed by reduction with lithium alum-Nemo hydrides to give N-cyclopropylmethyl-6,14 endoethano-7-(2-hydroxy-2-methyl-2-ter-butyl)-tetrahydronorthebbrine (formula 7); reaction with potassium hydroxide at 210C to give N-cyclopropylmethyl-6,14-endoethano-7 (2-hydroxy-2-methyl-2-ter-butyl)-tetrahydronororipavine (formula 8).
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~2~Z~ 0~3 The drawbacks of the conventional process are first the methyl vinyl kitten required for preparing the-brine adduce it not always easily available. Secondly the thebaine adduce obtained through acrolein gives a purer product as compared to methyl vinyl kitten. Further the reduction of Pd/C proceeds quite smoothly for the thebaine adduce synthesized from acrolein.
This invention provides a novel simplified pro-cuss for the preparation of the compound N-cyclopropyl-methyl-6,14-endoethano-7-(2-hydroxy-2-methyl-2-terr-butyl)-tetrahydronororipavine, which overcomes the drawbacks ox the conventional process.
Accordingly the present invention is a process for the preparation of the compound N-cyclopropylmethyl-6, 14-endothano-7-(2-hydroxy-2-methyl-2-ter-butyl)-teetrahydro-nororipavine that comprises reacting thebaine with acrolein to undergo Diels-Alder reaction to give 6,14-endoethano-7-formyl-tetrahydrothebaine which is reacted with methyl magnesium iodide to give 6,14-endoethano-7-(2-hydroxy-2-methyl)-tetrahydrothebaine which is oxidized by reaction with potassium permanganate to give 6,14-endoethano-7-acetyl-tetrahydrothebaine which is hydrogenated using palladium catalyst to give 6,14-endoethano-7-acetyletra-hydrothebaine which is reacted with ter-butyl magnesium chloride to give 6,14-endoethano-7-(2-hydroxy-2-methyl-2-ter-butyl-tetrahydrothebaine which is reacted with cyanogen -"` lo Ox bromide to give N-cyano-6,14-endoethano-7-t2-hydroxy-2-methyl-1-2-ter-butyl)-tetrahydrothebaine which is dime thy-fated by treatment with potassium hydroxide in one pot 210C to give 6,14-endoethano-7-(2-hydroxy-2 methyl-2-terbutyl)-te~rahydronororipavine which on treatment with cyclopropyl methyl bromide gives the compound N-cyclopro-pylmethyl-6,14-endoethano-7-(2-hydroxy-2--methyl-2Tory-butyl)-tetrahydronororipavine.
The process of preparing the compound N-cyclo propylmethyl-6,14-endoethano-7-(2-hydroxy-2-methylliter butyl)-tetra-hydronororipavine according to the present invention may be shown as:
Ox In rZ I
I n h o o O O O
I I Lo O . C) Us o I m m TV
"o I Al ox $1 ;~:; m I
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I I It o o o O
I
X
~2~2~
The compound prepared according to this invention is therapeutically useful because of its power to effect the CONS, particularly through analgesic, sedative and anti-tussive effects and to antagonize the effect of narcotic drugs. The compound is marketed as a drug under the trade mark "Buprenorphine".
The following examples illustrate the preparation of the compound N-cyclopropylmethyl-6,14-endoethano-7-(2-hydroxy-2-met:hyl~2-texbutyl~-tetrahydxonororipaviire according to the present invention.
6,14-endoethano-7-formyl-tetrahydrothebaine (Formula 12) A mixture of thebaine (formula 11~ (6 g) and acrolein (20 ml) in Bunyan (25 ml) was reflexed over water bath for 12 hours. the solvent an unrequited acrolein were removed by distillation. The solid obtained was washed repeatedly with hexane. The adduce was separated from thebaine by recrystallization from the ethanol. Thebaine-acrolein adduce was obtained as a colorless crystalline solid mop.
109, 6 gm(85%)M:367; M+ 367.
-` LO Ox EXAMPLE _ 6/14-endoethano 7~(2-hydroxy-2-methyl)-tetrahydrothebaine (Formula 13) A solution of methyl magnesium iodide was prepared from magnesium (38.1 gym) in ether (300 ml) and methyliodie (1.94 gym) in ether (200 ml) and Bunsen (20 ml). The mix-lure was stirred for 2 hours, 6,14-endoethano-7-formyl-tetrahydrothebaine (100 gym) in Bunsen (500 ml) was added over 1 hour to the stirred mixture. After standing over-night the mixture was added to a saturated aqueous solution of ammonium chloride (5 lit.). The organic layer was separated and the aqueous layer was further extracted with ether. The solvent was removed to give 40 g of the desired product. Simple recrystallization from methanol gives a product having mop. 140Q, M:398.47; M+ 398.5.
6,14-endoethano-7-acetyl tetrahydrothebaine (Formula 14) 6,14-endoethano-7-acetyl tetrahydrothebaine (10 gym) was dissolved in 160 ml, acetone. Portions under stirring at room temperature potassium permanganate ~7.93 gym) was added. The next quantity was added only when the earlier quantity was utilized. Stirring was continued for 6 hours, after addition of potassium permanganate was over. The reaction mixture was filtered off Noah, washed well with hot acetone. The solvent was removed on water bath to 1;~3L2~0~
yield (9 gym) (95~) of the desired product mop 120, My 381.47; M+ 381.5.
6,14-endoethano-7-acetyltetrahydrothebaine Formula 15) 6,14-endoethano-7-acetyl tetrahydrothebaine (25 gym) is ethanol (500 ml) was stirred with 10% Pd/c l2.5 g) under hydrogen at 85 pi and 90C for 10-12 hours. The soul-lion was filtered from the catalyst and evaporated. The residue was recrystallized from methanol to give the required product (20 gym) mop. 134C~ M:383; My 383.
6/14-endoethano-7-(2-hydroxy~2-methyl-2-terbutyl)--twitter-hydrothebaine (Formula 16) 100 gym of 6,14-endoethano-7-acetyltetrahydrothebaine dissolved in 500 ml of Bunsen is added drops to a soul-lion of ter-butyl magnesium chloride from 85 g of magnet slum, 275 g of t-butylchloride in 1 lithe of dry ether.
The reaction mixture is stirred at room temperature for 8 hours and then decomposed under cooling with saturated ammonium chloride solution. The ether layer is separated dried over McCoy and evaporated to yield a residue 16 gym of 6,14-endoethano-7-(2-hydroxy-2-methyl-2-terbutyl) twitter-hydrothebaine, mop. 180-189~C.
N-cyano~6,14-endoethano-7-~2-hydroxy-2-methyl-2-teerbutyl)-tetrahydrothebaine (Formula 17) The Grignard product (formula lug) obtained from Example 5 (50 gym) is dissolved in 250 ml of chloroform. Cyanogen bromide (30 gym) is added and the mixture is reflexed for 8 hours. The chloroform was evaporated and the residue was recrystallized from -ethics ethanol, when the N-cyano-nor compound (38 gym) was obtained with mop. 205C.
6,14-endoethano-7-(2-hydroxy-2-methyl-2-ter-butyl~~ twitter-_ _ hydronororipavine (Formula 18 The Grignard product (formula 16) obtained from Example 5 (50 gym) is dissolved in 250 ml of chloroform. Cyanogen bromide (30 gym) is added and the mixture is reflexed for 8 hours. The chloroform was evaporated and the residue was recrystallized from -ethics ethanol, when the N-cyano-nor compound ~38 gym) was obtained with mop. 205C, was added to a vigorously stirred mixture of 30 gym of potassium hydroxide in 300 ml, of diethylene glycol at 170C. The reaction mixture is maintained at 170C. for 8 hours. The reaction mixture is decomposed with ten times, its volume by ice cold water. The precipitated solid is filtered, washed with water and dried. The northebaine 12 gym is obtained with mop. 162-169C.
~231 I
N-cycloProp~lmethyl-6,l4-endoethano-7-(2 hydroxY-2-methy~=
2~ter-butyl)-tetrahydronororipavine (Formula_ 9 6,14-endoethano-7-(2-hydroxy-2-methyl-2-ter-butyl)twitter-hydronororipavine (4 gym) was dissolved in dim ethyl for-Muhammad (150 ml) and an hydrous potassium carbonate (8 gym) was added Cyclopropylmethyl bromide (7.5 gym) was added drops and the reaction temperature slowly raised to 80C. Heating at 80C under stirring was maintained for 4 hours. The dim ethyl formamide was then evaporated under vacuum, water was added and product extracted with ether.
The solvent on evaporation gave (2.5 gym) of the desired product mop 209C.
The solvent on evaporation gave (2.5 gym) of the desired product mop 209C.
Claims
1. The process for the preparation of the com-pound N-cyclopropylmethyl-6,14-endoethano-7-(2-hydroxy-2-methyl-2-ter-butyl)-tetrahydronororipavine which comprises reacting thebaine with acrolein to undergo Diels-Alder reaction to give 6,14-endoethano-7-formyl-tetrahydrothe-baine which is reacted with methyl magnesium iodide to give 6,14-endoethano-7-(2-hydroxy-2-methyl)-tetrahydrothebaine which is oxidized by reaction with potassium permangnante to give 6,14-endoethano-7-acetyl-tetrahydrothebaine which is hydrogenated using palladium catalyst to give 6,14-endoethano-7-acetyltetrahydrothebaine which is reacted with ter-butyl magnesium chloride to give 6,14-endoethano-7-(2-hydroxy-2-methyl-2-ter-butyl)-tetrahydrothebaine which is reacted with cyanogen bromide to give N-cyano-6,14-endoethano-7-(2-hydroxy-2-methyl-2-ter-butyl)-tetrahydro-thebaine which is reacted with cyanogen bromide to give N-cyano-6,14-endoethano-7-(2-hydroxy-2-methyl-2-terbutyl)-tetrahydrothebaine which is demethylated by treatment with potassium hydroxide in one pot at 210°C to give 6,14-endoethano-7-(2-hydroxy-2-methyl-2-ter-butyl)-tetra-hydronororipavine which on treatment with cyclo-propyl methyl bromide gives the compound N-cyclo-propylmethyl-6,14-endoethano-7-(2-hydroxy-2-methyl-2-ter-butyl)-tetra-hydronororipavine.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| IN259/BOM/83A IN156632B (en) | 1983-08-22 | 1983-08-22 | |
| IN259/BOM/83 | 1983-08-22 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA1212108A true CA1212108A (en) | 1986-09-30 |
Family
ID=11078963
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA000442036A Expired CA1212108A (en) | 1983-08-22 | 1983-11-28 | Process for the preparation of oripavine derivative |
Country Status (4)
| Country | Link |
|---|---|
| CA (1) | CA1212108A (en) |
| HU (1) | HU193563B (en) |
| IN (1) | IN156632B (en) |
| SU (1) | SU1362734A1 (en) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US8357802B2 (en) | 2006-10-17 | 2013-01-22 | Penick Corporation | Process for preparing oxymorphone |
| US9108974B2 (en) | 2006-10-17 | 2015-08-18 | Penick Corporation | Process for preparing oxymorphone, naltrexone, and buprenorphine |
| EP2344507B1 (en) | 2008-09-30 | 2015-11-11 | Mallinckrodt LLC | Processes for increasing the yield of the hydrolysis of the 3-o-methyl and 17-n-nitrile group in the preparation of opiate alkaloid derivatives |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| RU2503677C1 (en) * | 2012-08-21 | 2014-01-10 | Федеральное государственное бюджетное учреждение науки Институт элементоорганических соединений им. А.Н. Несмеянова Российской академии наук (ИНЭОС РАН) | 3,6-dimethoxy-17-methyl-7alpha-(trifluoroacetyl)-4,5alpha-epoxy-6alpha, 14alpha-ethenoisomorphinane and method for production thereof |
-
1983
- 1983-08-22 IN IN259/BOM/83A patent/IN156632B/en unknown
- 1983-11-28 CA CA000442036A patent/CA1212108A/en not_active Expired
-
1984
- 1984-03-29 HU HU841261A patent/HU193563B/en not_active IP Right Cessation
- 1984-05-21 SU SU843741238A patent/SU1362734A1/en active
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US8357802B2 (en) | 2006-10-17 | 2013-01-22 | Penick Corporation | Process for preparing oxymorphone |
| US9108974B2 (en) | 2006-10-17 | 2015-08-18 | Penick Corporation | Process for preparing oxymorphone, naltrexone, and buprenorphine |
| US9487532B2 (en) | 2006-10-17 | 2016-11-08 | Penick Corporation | Process for preparing oxymorphone, naltrexone, and buprenorphine |
| EP2344507B1 (en) | 2008-09-30 | 2015-11-11 | Mallinckrodt LLC | Processes for increasing the yield of the hydrolysis of the 3-o-methyl and 17-n-nitrile group in the preparation of opiate alkaloid derivatives |
| EP2344507B2 (en) † | 2008-09-30 | 2021-05-26 | Mallinckrodt LLC | Processes for increasing the yield of the hydrolysis of the 3-o-methyl and 17-n-nitrile group in the preparation of opiate alkaloid derivatives |
Also Published As
| Publication number | Publication date |
|---|---|
| HU193563B (en) | 1987-10-28 |
| HUT39452A (en) | 1986-09-29 |
| SU1362734A1 (en) | 1987-12-30 |
| IN156632B (en) | 1985-09-21 |
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