Controlled design of resolutions. Prediction of the efficiency of resolutions based on samples of arbitrary composition

The rational design of resolution processes is a topic of common interest for the industrial synthesis of enantiopure compounds. However, no efficient method for selecting suitable resolving agents for classical resolution using diastereomeric salts is available yet(1) and the selection of an appropriate resolving agent usually is a matter of trial and error. This article describes an approach using single differential scanning calorimetry (DSC) measurements on mixtures of diastereomers with arbitrary (non-racemic) compositions, with the aim of allowing a more systematic identification of efficient resolving agents and to minimize the possible errors due to uncontrolled experimental factors in the search for resolving agents. It is shown that in many cases a single DSC thermogram can provide valuable information about the maximal possible efficiency of an enantiomer resolution via diastereomeric salts. (C) 1998 Elsevier Science Ltd. All rights reserved.