Resolution by Preferential Crystallization of Proxyphylline by Using Its Salicylic Acid Monohydrate Co‐Crystal

The monohydrated co‐crystal composed of the chiral active pharmaceutical ingredient proxyphylline, salicylic acid, and water was successfully resolved by preferential crystallization from a water/ethanol mixture. To the best of our knowledge, this is the first report of preferential crystallization applied to such a system and the results reveal that unusually high enantiomeric excess values can be attained in the mother liquor. These robust and reproducible results underline the potential of preferential crystallization to resolve co‐crystal systems. Production of pure enantiomers is of high interest in the pharmaceutical industries. Preferential crystallization is a very efficient technique designed to separate enantiomers forming a conglomerate system. The first example of applying this method to a conglomerate co‐crystal of a racemic compound is highlighted, showing the high productivity and high yield of the process.