Patent ID: 9206220
Filing Date: 2015-12-08
Classification: C07J

Abstract:
1. A process for the synthesis of ursodeoxycholic acid, said process comprising the following steps: (I) preparing methyl 3α,7α-diacetoxy-12α-hydroxycholanate through the esterification of cholic acid to obtain the methyl cholate intermediate which is not isolated and is acetylated in position 3 and 7 to obtain the methyl 3α,7α-diacetoxy-12α-hydroxycholanate intermediate which is isolated by crystallisation; (II) preparing methyl 3α,7α-diacetoxy-12-ketocholanate through oxidisation of the methyl 3α,7α-diacetoxy-12α-hydroxycholanate intermediate on the hydroxyl group in position 12 to give the methyl 3α,7α-diacetoxy-12-ketocholanate intermediate which is isolated by crystallisation; (III) preparing the crude chenodeoxycholic acid through Wolff-Kishner reduction of the ketone group in position 12 of the methyl 3α,7α-diacetoxy-12-ketocholanate intermediate, and reacting by means of hydrolysis the ester groups in position 3,7 and 24 to obtain the crude chenodeoxycholic acid; (IV) preparing the 3α-hydroxy-7-ketocholanic acid through oxidisation of the hydroxyl group in position 7 present on the crude chenodeoxycholic acid intermediate, to give 3α-hydroxy-7-ketocholanic acid; (V) preparing the ursodeoxycholic acid imidazole salt through reduction of the ketone group present in position 7 of the 3α-hydroxy-7-ketocholanic acid intermediate to give the crude ursodeoxycholic acid in the form of a mixture of ursodeoxycholic acid and chenodeoxycholic acid then treating with imidazole to give the ursodeoxycholic acid imidazole salt which is isolated by crystallisation; (VI) preparing the ursodeoxycholic acid methyl ester through esterification of the ursodeoxycholic acid imidazole salt intermediate to give the ursodeoxycholic acid methyl ester which is isolated by crystallisation; (VII) preparing the ursodeoxycholic acid through hydrolysis of the ursodeoxycholic acid methyl ester intermediate, then acidifying to give the ursodeoxycholic acid.