Development and Kinetic Modeling of Continuous‐Flow Asymmetric Hydrogenation With Integrated Catalyst Recycling

ABSTRACT In the development of economic competitive and sustainable pharmaceutical manufacturing with homogeneous catalysts, catalyst recovery is a key step toward efficient and scalable processes, as it directly impacts process efficiency and economic feasibility. In this study, we demonstrate the integration of organic solvent nanofiltration (OSN) into a continuous asymmetric hydrogenation of benzylphenylephrone (BPE) to enable catalyst recycling and process intensification. This is coupled with kinetic modeling for in silico investigation of the established process. Membrane screening identified PuraMem Flux as the most suitable material, achieving >90% catalyst retention under operating conditions. Catalyst recycling experiments revealed a reproducible activity loss of ∼10% per cycle, which was incorporated into the mathematical model and validated in recirculation operation. Scale‐up to a 59.4 mL tubular reactor with an integrated unit for OSN confirmed the accuracy of the model and demonstrated stable operation with consistently high enantiomeric excess (87%–90% ee). Comparative evaluation of single‐pass and recirculation operation highlighted the benefits of catalyst recycling, with yields increased from 69.1% to 86.8%, while space–time yield (STY) improved by over 20%. Together, these findings establish continuous asymmetric hydrogenation with catalyst recycling via OSN as a promising route, providing a robust foundation for efficient and sustainable pharmaceutical manufacturing.