Recovery and reuse of homogeneous palladium catalysts via organic solvent nanofiltration: application in the synthesis of AZD4625

Abstract

Homogeneous catalysts are frequently used in the pharmaceutical industry but suffer from problematic separation from the reaction mixture and subsequent reuse. As an alternative to traditional separation methods like distillation and extraction, organic solvent nanofiltration (OSN) shows great potential to address the challenge of efficiently recovering and reusing homogeneous catalysts, without high energy usage and cumbersome biphasic separation. Here, we demonstrate the effective recovery of homogeneous palladium catalysts from the reaction mixture using commercial OSN membranes in a real pharmaceutical manufacturing case study to synthesize AZD4625, without altering the existing catalyst/ligand system. Despite the inherent challenges, the recovered catalyst and ligand were successfully reused up to five times, maintaining high conversion of over 90%. Furthermore, life cycle assessment shows that the sustainability of the process could be further enhanced by using greener bio-derived solvents and implementing solvent recovery to reduce solvent consumption.