Combining incompatible processes for deracemization of Praziquantel derivative under flow conditions

Giulio Valenti, Paul Tinnemans, Iaroslav Baglai, Willem L. Noorduin, Bernard Kaptein, Michel Leeman, Joop H. ter Horst, Richard M. Kellogg

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)5279-5282
Number of pages4
JournalAngewandte Chemie - International Edition
Volume60
Issue number10
Early online date26 Nov 2020
DOIs
Publication statusPublished - 1 Mar 2021

Keywords

  • chirality
  • flow chemistry
  • heterogeneous catalysis
  • racemization
  • schistosomiasis

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