发明名称 |
Process for preparing high purity ursodeoxycholic acid |
摘要 |
The present invention describes a process for the synthesis of ursodeoxycholic acid wherein the purification of the crude ursodeoxycholic acid (containing approximately 13-15% of chenodeoxycholic acid impurity) takes place first passing through a salification with imidazole and a subsequent purification via “methyl ester”, which allows a finished product with an extremely low content of known “cheno and “litho” impurities to be obtained. The present invention also describes the recovery steps of cholic acid and 3α-hydroxy-7-ketocholanic acid from the mother liquors of process intermediates. |
申请公布号 |
US9206220(B2) |
申请公布日期 |
2015.12.08 |
申请号 |
US201314418296 |
申请日期 |
2013.07.30 |
申请人 |
Erregierre S.p.A. |
发明人 |
Ferrari Massimo;Zinetti Fabrizio |
分类号 |
C07J9/00;C07J75/00 |
主分类号 |
C07J9/00 |
代理机构 |
Ohlandt, Greeley, Ruggiero & Perle, L.L.P. |
代理人 |
Ohlandt, Greeley, Ruggiero & Perle, L.L.P. |
主权项 |
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. |
地址 |
San Paolo d'Argon IT |