Use of achiral/chiral SFC/MS for the profiling of isomeric cinnamonitrile/hydrocinnamonitrile products in chiral drug synthesis.

A directly coupled achiral/chiral SFC/MS method has been developed for the profiling of a three-step stereoselective synthesis of cinnamonitrile and hydrocinnamonitrile intermediates. Semipurified reaction mixtures were screened in one step to determine the diastereomeric/enantiomeric composition of the final product as well as to identify any remaining E/Z isomers present from the starting material. The coupled achiral/chiral column combination was found to significantly enhance the separation of both enantiomers and diastereomers, without adding significantly to the overall analysis time. This analytical technique should prove to be generally useful for the profiling of isomeric reaction products in chiral drug synthesis.