Large-Scale Candoxatril Asymmetric Hydrogenation

Abstract

Ruthenium-catalyzed asymmetric hydrogenation was used to prepare tons of a key chiral succinate intermediate for clinical trials quantities of candoxatril. MeOBiphep was used as the ligand, and the catalyst was generated in situ from RuCODBismethylallyl. THF was the best cosolvent for the reaction leading to a selective hydrogenation and a process which was readily amenable on large scale.