Optimization of the cooling profile to improve the filterability of crystals isolated during an optical resolution by diastereomeric salt formation

The crystallization of a diastereomeric salt during the optical resolution of a synthesized intermediate led to crystals showing poor filterability. With a view to decrease the duration of the filtration step, linear cooling profiles, including a preliminary stabilization step, and non-linear cooling profiles (quoted as controlled type) are tested. This latter type of profile enables a significant increase of mother liquors flowrate during filtration (from 50% to 300% according to crystallization duration). Scanning Electron Microscopy observations of crystals confirmed the trends deducted from the comparison of mean mother liquors flowrates: the promotion of crystal growth over nucleation leads to wider (and fewer small) crystals exhibiting an improved filterability.