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Combining Incompatible Processes for Deracemization of a Praziquantel Derivative under Flow Conditions
Author(s) -
Valenti Giulio,
Tinnemans Paul,
Baglai Iaroslav,
Noorduin Willem L.,
Kaptein Bernard,
Leeman Michel,
ter Horst Joop H.,
Kellogg Richard M.
Publication year - 2021
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.202013502
Subject(s) - racemization , crystallization , enantiomer , derivative (finance) , enantioselective synthesis , dissolution , combinatorial chemistry , chemistry , materials science , chemical engineering , organic chemistry , catalysis , financial economics , economics , engineering
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.