Large-scale candoxatril asymmetric hydrogenation

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 RuCOD-Bismethylallyl. THF was the best cosolvent for the reaction leading to a selective hydrogenation and a process which was readily amenable on large scale.