Substrate Modification Approach to Achieve Efficient Resolution:  Didesmethylcitalopram:  A Key Intermediate for Escitalopram

Abstract

Research work presented here describes an approach to achieve the enantiopure escitalopram ( 1 ) via didesmethyl escitalopram ( 4 ), which is easily resolvable compared to citalopram ( 1a ) through diastereomeric salt crystallization. The resolved intermediate (didesmethylcitalopram) was subsequently used for the preparation of the desired drug. This simple modification of the substrate makes a remarkable difference in the chemical resolution process. The first resolution of didesmethylcitalopram (±)- 4 to furnish (+)- 4, a novel key intermediate to assemble escitalopram ( 1 ) was achieved via diastereomeric salt resolution using (−)-di- p -toluoyltartaric acid (DPTTA). The resolution conditions were optimized; a key feature of this process is the addition of specific quantity of water at a specific temperature to the reaction mixture.