Simultaneous chiral resolution of two racemic compounds by preferential cocrystallization

Zhou, Fuli and Shemchuk, Oleksii and Charpentier, Maxime D. and Matheys, Chloé and Collard, Laurent and ter Horst, Joop H. and Leyssens, Tom (2021) Simultaneous chiral resolution of two racemic compounds by preferential cocrystallization. Angewandte Chemie - International Edition, 60 (37). pp. 20264-20268. ISSN 1433-7851 (https://doi.org/10.26434/chemrxiv.14730537.v1)

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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.

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