LAUSR

The preparative resolution by preferential crystallization (PC) of proxyphylline has been achieved despite the existence of a stable racemic compound. This is enabled through the careful selection of a solvent in which both the racemic compound and the metastable conglomerate possess a low nucleation rate. Induction time measurements in isobutyl alcohol show that a highly supersaturated solution (beta= 2.3) remains clear for almost 1 hour at 20 mL scale, revealing a slow nucleation rate. After the determination of isothermal sections in the relevant phase diagram at 10 and 25 °C, both isothermal and polythermic modes of PC could be successfully implemented. Alongside the reported case of diprophylline, this study opens opportunities to broaden the application of PC towards slowly crystallizing ra-cemic compound.