A Novel Method for Resolution of Amlodipine

被引：43

作者：

Gotrane, Dinkar M. ^{[1
]}

Deshmukh, Rajendra D. ^{[1
]}

Ranade, Prasad V. ^{[1
]}

Sonawane, Swapnil P. ^{[1
]}

Bhawal, Baburao M. ^{[1
]}

Gharpure, Milind M. ^{[1
]}

Gurjar, Mukund K. ^{[1
]}

机构：

[1] Emcure Pharmaceut Ltd, API R&D Ctr, MIDC, Pune 411057, Maharashtra, India

来源：

ORGANIC PROCESS RESEARCH & DEVELOPMENT | 2010年 / 14卷 / 03期

关键词：

CALCIUM-ANTAGONISTS;

D O I：

10.1021/op900283z

中图分类号：

O69 [应用化学];

学科分类号：

081704 ;

摘要：

The present invention relates to an industrially feasible and cost-efficient process for the preparation of isomerically pure Samlodipine besylate hemipentahydrate (1), a useful calcium antagonist inhibitor. Previous workers reported that R-amlodipinetartrate was crystallized out preferentially from the reaction mixture when naturally occurring t-tartaric acid and racemic amlodipine base in DMSO are mixed. In order to crystallize S-amlodipine-tartrate, the use of unnatural D-tartaric acid as a resolving agent in DMSO was required. However, the cost of D-tartaric acid was not conducive to overall cost efficiency in the resolution protocol. Subsequent to the above observations, we have developed a novel resolving system in which amlodipine base with natural L"tartaric acid in DMF as a solvent gave preferentially the S-form of amlodipine tartrate directly from the reaction. The optimization of this approach by adjusting the water percentage in DMF ensured consistent purity of S-amlodipine (+99%) and satisfactory resolution efficiency.

引用

页码：640 / 643

页数：4

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