An efficient deracemization method for conversion of the racemate to the desirable ( R )‐enantiomer has been developed by coupling incompatible racemization and crystallization processes. By a library approach a derivative that crystallizes as a conglomerate in the solid phase has been identified. Racemization occurs via reversible hydrogenation over a palladium on carbon (Pd/C) packed column at 130 °C, whereas deracemization is achieved by alternating crystal growth/dissolution steps with temperature cycling between 5‐15 °C. These incompatible processes are combined by means of a flow system. Complete deracemization of the solid phase to the desired ( R )‐enantiomer (98% ee) takes place. 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.

Wiley VCH
European Union Horizon 2020
Angew. Chem. Int. Ed.
Self-Organizing Matter

Valenti, G, Tinnemans, P, Baglai, I, Noorduin, W.L, Kaptein, B, Leeman, M, … Kellogg, R.M. (2021). Combining incompatible processes for deracemization of a Praziquantel derivative under flow conditions. Angew. Chem. Int. Ed., 60(10), 5279–5282. doi:10.1002/anie.202013502