1198213-96-5Relevant articles and documents
Pasteur's Tweezers revisited: On the mechanism of attrition-enhanced deracemization and resolution of chiral conglomerate solids
Hein, Jason E.,Huynh Cao, Blessing,Viedma, Cristobal,Kellogg, Richard M.,Blackmond, Donna G.
, p. 12629 - 12636 (2012)
Insights into the mechanism of attrition-enhanced deracemization and resolution of solid enantiomorphic chiral compounds are obtained by crystal size and solubility measurements and by isotopic labeling experiments. Together these results help to deconvolute the various chemical and physical rate processes contributing to the phenomenon. Crystal size measurements highlight a distinct correlation between the stochastic, transient growth of crystals and the emergence of a single solid enantiomorph under attrition conditions. The rapid mass transfer of molecules between the solution and solid phases under attrition is demonstrated, and the concept of a crystal-size-induced solubility driving force is exploited to overcome the stochastic nature of the crystal growth and dissolution processes. Extension to non-racemizing conditions provides a novel methodology for chiral resolution. Implications both for practical chiral separations and for the origin of biological homochirality are discussed.
Attrition-enhanced deracemization in the synthesis of clopidogrel - A practical application of a new discovery
Van Der Meijden, Maarten W.,Leeman, Michel,Gelens, Edith,Noorduin, Wim L.,Meekes, Hugo,Van Enckevort, Willem J.P.,Kaptein, Bernard,Vlieg, Elias,Kellogg, Richard M.
experimental part, p. 1195 - 1198 (2010/04/22)
The recently discovered technique of deracemization by means of attrition-induced grinding of a solid conglomerate in contact with a solution wherein racemization occurs has been used with a derivative of 2-chlorophenyl glycine, the key chiral component in the synthesis of Clopidogrel (Plavix). Deracemization of the racemate proceeds to a single enantiomer and in essentially absolute enantiomeric excess. Further conversion of enantiomerically pure material to Clopidogrel was achieved in 88% yield.
