Enantioselective synthesis of (-)-(R) Silodosin by ultrasound-assisted diastereomeric crystallization

Abstract

Enantioselective synthesis of clinically approved drug Silodosin for the treatment of benign prostatic hyperplasia from the commercially available compounds 1-acetyl-5-(2-aminopropyl) indoline-7-carbonitrile A and 2-(2-(2,2,2-trifluoroethoxy)phenoxy)ethyl methanesulfonate C is explored. Key step in the synthesis is chiral resolution of intermediate I, which was achieved by a simple diastereomeric crystallization using (S)-(+)-mandelic acid assisted by ultrasonication. The present synthetic strategy has lesser number of steps and is vastly improved the overall yield in this short route towards target compound Silodosin. (C) 2013 Elsevier Ltd. All rights reserved.