Chiral resolution of racemic amines in μ-reactor-crystallizer

The production of pure chiral drugs in a continuous manner is one of the major issues for pharmaceutical industries. A micro continuous process is developed for chiral separation of racemic molecules exploiting a "classical" method of diastereomer formation and subsequent crystallization. A flexible mm-reactor and m-crystallizer are fabricated for the continuous production of diastereomer salt crystals from racemic a-phenylethylamine (I) where optically active L-(+)-tartaric acid (II) is used as a resolving agent. CD spectroscopy, UV-Vis spectroscopy, and other characterizations confirm that the diastereomeric salt obtained from the micro-continuous process is similar in quality if not better than that obtained from a conventional batch process. The process described here is capable to produce crystals at similar to 33 times faster than the batch process at identical feed concentrations. The better control over crystals and faster resolution in this low-cost micro-continuous process offer industries a potential route for production through verylarge-scale integration (VLSI). (C) 2022 Elsevier Ltd. All rights reserved.