Efficient Stereoselective Reduction in the Synthesis of Eslicarbazepine Acetate by Employing Design of Experiments

Asymmetric hydrogenation is one of the key strategies for achieving the stereoselective synthesis of pharmaceuticals. In the synthesis of eslicarbazepine acetate, a stereoselective reduction approach was employed to convert oxcarbazepine into eslicarbazepine with 99% ee and 93% yield. This article provides a comprehensive, complementary density functional theory (DFT) calculation to gain mechanistic insight into the observed high enantioselectivity. Furthermore, crystallographic analysis of the final product offers distinctive evidence of a stereochemical outcome. By employing Quality by Design (QbD) principles and Design of Experiments (DoE), we identified the critical quality attributes (CQAs) and established relationships among material attributes (MAs), critical process parameters (CPPs), and CQAs. Environmental impact was assessed using green metrics to ensure process sustainability. This study also highlights an efficient, scalable, and robust process, developed through DoE techniques to afford eslicarbazepine acetate with 99.9% ee and 81% yield.