A novel method for resolution of amlodipine

Abstract

The present invention relates to an industrially feasible and cost-efficient process for the preparation of isomerically pure S-amlodipine besylate hemipentahydrate (1), a useful calcium antagonist inhibitor. Previous workers reported that R-amlodipine-tartrate was crystallized out preferentially from the reaction mixture when naturally occurring L-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.