Patent ID: 9108974
Filing Date: 2015-08-18
Classification: A61K,A61P,C07D

Abstract:
1. A method of preparing buprenorphine or a salt thereof from oripavine comprising: reacting the oripavine with methyl vinyl ketone to produce 7α-acetyl-6,7,8,14-tetrahydro-6,14-endoethenooripavine; protecting a hydroxyl group of 7α-acetyl-6,7,8,14-tetrahydro-6,14-endoethenooripavine with a benzyl group to 7α-acetyl-3-benzyl-6,7,8,14-tetrahydro-6,14-endoethenooripavine; de-methylating the 7α-acetyl-3-benzyl-6,7,8,14-tetrahydro-6,14-endoethenooripavine with ACE-Cl to 7α-acetyl-3-benzyl-6,7,8,14-tetrahydro-6,14-endoethenonororipavine; alkylating the 7α-acetyl-3-benzyl-6,7,8,14-tetrahydro-6,14-endoethenonororipavine with (chloromethyl)cyclopropane to obtain 7α-acetyl-3-benzyl-17-cyclopropylmethyl-6,7,8,14-tetrahydro-6,14-endoethenonororipavine; reacting the 7α-acetyl-3-benzyl-17-cyclopropylmethyl-6,7,8,14-tetrahydro-6,14-endoethenonororipavine with tert-butyl magnesium chloride or tert-butyl lithium to produce 3-benzyl-17-cyclopropylmethyl-6,14-endo-etheno-7α-(2-hydroxy-3,3-dimethyl-2-butyl)-6,7,8,14-tetrahydronororipavine; and reducing the 3-benzyl-17-cyclopropylmethyl-6,14-endo-etheno-7α-(2-hydroxy-3,3-dimethyl-2-butyl)-6,7,8,14-tetrahydronororipavine by catalytic hydrogenation to produce buprenorphine.