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US 2014/0235860 A1Published application
Method of preparing buprenorphine
AssigneeJohnson Mattey Public Limited Company
InventorsNicolas Archer, David August, Michael Bease, Barbara Jamieson, Robert S. Marmor
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Abstract
An improved process for preparing buprenorphine and a method for increasing the yield of buprenorphine or a derivative thereof.
Claims31
A process for the preparation of buprenorphine comprising the following steps:
- wherein:
- a. the solvent of step 5A is an alcohol.
- b. the M1 moiety in step 5A is an alkali metal;
- and
- wherein steps 5A, 5B, and 5C occur at mild conditions.
2 more elements
The process of step 10, wherein the drying step occurs in a vacuum oven at about 60° to about 85° C.
A process for the preparation of a compound of formula (Ib),
- wherein:
- R10 is a straight-chain, branched or cyclic C1-C20 alkyl;
- R11 is —C(R13)(R14)(OH) or a protected —C(═O)(R15);
- R12 is H or CN;
- R13 is a straight-chain, branched or cyclic C1-C20-alkyl;
- R14 is a straight-chain, branched or cyclic C1-C20-alkyl;
- and
- R15 is a straight-chain, branched or cyclic C1-C20-alkyl
- is a double bond or a single bond;
- the process comprising:
- i. reacting a compound of formula (Ia) with a thiolate in a suitable polar aprotic solvent, wherein the thiolate is selected from the group consisting of an optionally substituted C1-C20-alkylthiolate, an optionally substituted C6-C20-arylthiolate or an optionally substituted C7-C30-arylalkylthiolate;
- and
- ii. treating the reaction mixture of step (i) with a protonating agent to give the compound of formula (Ib).
10 more elements
A process for the preparation of a compound of formula (IIb),
- wherein:
- R20 and R21 are independently selected from substituted or unsubstituted C1-C20 alkyl, or R20 and R21 are interconnected to form a ring;
- R22 is H or OH;
- R23 is selected from the group consisting of H, CN, substituted C1-C20 alkyl, unsubstituted C1-C20 alkyl, substituted C4-C20-alkyl-cycloalkyl, unsubstituted C4-C20-alkyl-cycloalkyl and allyl;
- is a double bond or a single bond;
- the process comprising:
- i. reacting a compound of formula (IIa) with a thiolate in a suitable polar aprotic solvent, wherein the thiolate is selected from the group consisting of an optionally substituted C1-C20-alkylthiolate, an optionally substituted C6-C20-arylthiolate or an optionally substituted C7-C30-arylalkylthiolate;
- and
- ii. treating the reaction mixture of step (i) with a protonating agent to give the compound of formula (IIb).
6 more elements
A process for the preparation of a compound of formula (IIIb),
- wherein:
- R30 is an alcohol protecting group;
- R31 is H or OH;
- and
- R32 is selected from the group consisting of H, CN, substituted C1-C20 alkyl, unsubstituted C1-C20 alkyl, substituted C4-C20-alkyl-cycloalkyl, unsubstituted C4-C20-alkyl-cycloalkyl and allyl;
- the process comprising:
- i. reacting a compound of formula (IIIa) with a thiolate in a suitable polar aprotic solvent, wherein the thiolate is selected from the group consisting of an optionally substituted C1-C20-alkylthiolate, an optionally substituted C6-C20-arylthiolate or an optionally substituted C7-C30-arylalkylthiolate;
- and
- ii. treating the reaction mixture of step (i) with a protonating agent to give the compound of formula (IIIb).
6 more elements
Dependencies are inferred from the claim text.