Combining Incompatible Processes for Deracemization of a Praziquantel Derivative under Flow Conditions

An efficient deracemization method for conversion of the racemate to the desirable (R)-enantiomer of Praziquantel has been developed by coupling incompatible racemization and crystallization processes. By a library approach, a derivative that crystallizes as a conglomerate has been identified. Racemization occurs via reversible hydrogenation over a palladium on carbon (Pd/C) packed column at 130 degrees C, whereas deracemization is achieved by alternating crystal growth/dissolution steps with temperature cycling between 5-15 degrees C. These incompatible processes are combined by means of a flow system resulting in complete deracemization of the solid phase to the desired (R)-enantiomer (98 % ee). Such an unprecedented deracemization by a decoupled crystallization/racemization approach can readily be turned into a practical process and opens new opportunities for the development of essential enantiomerically pure building blocks that require harsh methods for racemization.

Automated summary

An efficient method for deracemization of a racemate to the desired (R)-enantiomer of Praziquantel has been developed by coupling incompatible racemization and crystallization processes. Through a library approach, a derivative that crystallizes as a conglomerate has been identified, and using a flow system, the incompatible processes have been combined to achieve complete deracemization to the desired (R)-enantiomer.