Synthesis of Mirabegron via Late-Stage Cu-Catalyzed Aromatic Amidation

Abstract

A practical synthesis of mirabegron, a first-line drug for the treatment of overactive bladder, was developed. This synthetic route avoids the use of structural alerts such as aniline and nitrobenzene, which raise concerns regarding human exposure during large-scale synthesis. This strategy relies on the Cu-catalyzed coupling between an aryl halide and an amide derivative, which was successfully conducted on a gram scale by selecting a suitable diamine ligand and an appropriate protecting group for the amine.