Concise Synthesis of Key Intermediate of Mirabegron via a Mixed Anhydride Method

Abstract

An efficiently scalable synthesis of key intermediate toward mirabegron has been developed via a mixed anhydride method, employing PivCl instead of EDCI and HOBt. The developed process produced ( R )-2-hydroxy- N -(4-nitrophenethyl)-2-phenylacetamide ( 10 ) in 91.5–92.3% yield and >99.0% HPLC purity under mild conditions. During this process, a side reaction induced by triethylamine hydrochloride was discovered and investigated, which was ultimately avoided by executing the reaction in a biphasic solvent system.