发明名称 |
Process for the preparation of nateglinide |
摘要 |
The present invention relates to a process for the preparation of substantially pure nateglinide of formula (I), substantially free from the cis-isomer and L-enantiomer and preparation of enantiomerically pure nateglinide form B, directly from the hydrolysis of a (−)-N-(trans-4-isopropylcyclohexyl-1-carbonyl)-D-phenylalanine alkyl ester in a ketonic solvent or water or mixture thereof. |
申请公布号 |
US9150499(B2) |
申请公布日期 |
2015.10.06 |
申请号 |
US201113703758 |
申请日期 |
2011.06.14 |
申请人 |
Cipla Limited |
发明人 |
Kankan Rajendra Narayanrao;Rao Dharmaraj Ramachandra;Birari Dilip Ramdas |
分类号 |
C07C229/00;C07C231/12 |
主分类号 |
C07C229/00 |
代理机构 |
Conley Rose, P.C. |
代理人 |
Conley Rose, P.C. ;Carroll Rodney B. |
主权项 |
1. A process for preparing nateglinide of formula (I) or a pharmaceutically-acceptable salt thereof, wherein the nateglinide is polymorphic Form B, which process comprises: preparing (−)-N-(trans-4-isopropylcyclohexyl-1-carbonyl)-D-phenylalanine alkyl ester of formula (II) by condensation of a D-phenylalanine alkyl ester of formula (IV) or an acid addition salt thereof with trans-4-isopropyl-cyclohexylcarboxylic acid of formula (III) in the presence of a condensation solvent, an alkali metal hydroxide and a condensing agent to form a (−)-N-(trans-4-isopropylcyclohexyl-1-carbonyl)-D-phenylalanine alkyl ester of formula (II) without intermediate conversion to an acid chloride or an N-hydroxysuccinmide ester, of formula (III) wherein the Alk group is a C1-C4 alkyl group; and hydrolysis of compound (II) in the presence of a hydrolysis solvent, wherein the hydrolysis solvent is a mixture of a ketone and water, and the ketone:water ratio varies from 5:1 to 1:1 v/v; and optionally conversion of the nateglinide (I) to a salt thereof. |
地址 |
Mumbai IN |