Heart-Cutting Two-Dimensional Ultrahigh-Pressure Liquid Chromatography for Process Development: Asymmetric Reaction Monitoring

This contribution presents the first application of two-dimensional, ultrahigh-pressure liquid chromatography (2D-UHPLC) for monitoring asymmetric reactions in process development. Several asymmetric transformations were studied to illustrate the operation of the instrument and evaluate the performance of 2D-UHPLC. Two-dimensional UHPLC is particularly advantageous because it allows a simultaneous analysis of the reaction conversion and its enantiomeric excess. By employing UHPLC the analysis time can be reduced significantly, and the achiral–chiral 2D coupling approach allows for direct injection of the reaction mixture. This study demonstrates the utility of 2D-UHPLC in asymmetric transformations for drug development