Asymmetric catalytic hydrogenation for large scale preparation of optically active 2-(N-benzoylamino)cyclohexanecarboxylic acid derivatives

Abstract

Asymmetric catalytic hydrogenation methodology was applied to the synthesis of 2-[N-(4-difluoromethoxy)benzoylamino]cyclohexanecarboxylic acid derivatives. During the course of optimization, it was found that chiral Ru(II) dicarboxylate complexes worked efficiently with an acid additive, aqueous HBF₄. Regarding chiral ligand, DTBM-BINAP showed the best result with full-conversion and the highest stereoselectivity. Practical conditions for the asymmetric hydrogenation were also established suppressing the amount of the catalyst and multi-kilogram scale synthesis was successfully achieved.