Combining incompatible processes for deracemization of Praziquantel derivative under flow conditions

Valenti, Giulio and Tinnemans, Paul and Baglai, Iaroslav and Noorduin, Willem L. and Kaptein, Bernard and Leeman, Michel and ter Horst, Joop H. and Kellogg, Richard M. (2021) Combining incompatible processes for deracemization of Praziquantel derivative under flow conditions. Angewandte Chemie - International Edition, 60 (10). pp. 5279-5282. ISSN 1521-3773 (https://doi.org/10.1002/anie.202013502)

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Abstract

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 °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 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.

ORCID iDs

Valenti, Giulio, Tinnemans, Paul, Baglai, Iaroslav, Noorduin, Willem L., Kaptein, Bernard, Leeman, Michel, ter Horst, Joop H. ORCID logoORCID: https://orcid.org/0000-0003-0118-2160 and Kellogg, Richard M.;
CORE (COnnecting REpositories)