Simultaneous Chiral Resolution of Two Racemic Compounds by Preferential Cocrystallization*

Fuli Zhou; Oleksii Shemchuk; Maxime D Charpentier; Chloé Matheys; Laurent Collard; Joop H Ter Horst; Tom Leyssens

doi:10.1002/anie.202107804

Simultaneous Chiral Resolution of Two Racemic Compounds by Preferential Cocrystallization*

Angew Chem Int Ed Engl. 2021 Sep 6;60(37):20264-20268. doi: 10.1002/anie.202107804. Epub 2021 Aug 6.

Authors

Fuli Zhou¹, Oleksii Shemchuk¹, Maxime D Charpentier², Chloé Matheys¹, Laurent Collard¹, Joop H Ter Horst^{2

3}, Tom Leyssens¹

Affiliations

¹ Institute of Condensed Matter and Nanosciences, Place Louis Pasteur, 1 bte L4.01.06, 1348, Louvain-La-Neuve, Belgium.
² EPSRC Centre for Innovative Manufacturing in Continuous Manufacturing and Crystallisation (CMAC), Strathclyde Institute of Pharmacy and Biomedical Sciences, Technology and Innovation Centre, University of Strathclyde, 99 George Street, Glasgow, G1 1RD, UK.
³ Laboratoire Sciences et Méthodes Séparatives, Université de Rouen Normandie, Place Emile Blondel, 76821, Mont Saint Aignan Cedex, France.

PMID: 34233036
DOI: 10.1002/anie.202107804

Abstract

We tap into an unexplored area of preferential crystallization, being the first to develop simultaneous chiral resolution of two racemic compounds by preferential cocrystallization. We highlight how the two racemic compounds RS-mandelic acid (MAN) and RS-etiracetam (ETI) can be combined together as enantiospecific R-MAN⋅R-ETI and S-MAN⋅S-ETI cocrystals forming a stable conglomerate system and subsequently develop a cyclic preferential crystallization allowing to simultaneous resolve both compounds. The developed process leads to excellent enantiopurity both for etiracetam (ee>98 %) and mandelic acid (ee≈95 %) enantiomers.

Keywords: chiral resolution; cocrystals; conglomerate; preferential crystallization; simultaneous resolution.

Publication types

Research Support, Non-U.S. Gov't