Catalytic asymmetric hydrogenation of enamides Problems and challenges on scale

This article illustrates the application of catalytic asymmetric hydrogenation of enamides in the large-scale synthesis of trans-norsertraline. Problems and challenges encountered during the development and scale-up of the process, as well as their resolution, are highlighted. Specifically, the efficient synthesis of enamide and the hydrolysis of resulting acetamide were recognized as major issues in the application of this powerful technology for the development of large-scale chemical processes to chiral amines.