mp9b00805_si_001.pdf (666.75 kB)
Enabling Direct Preferential Crystallization in a Stable Racemic Compound System
journal contribution
posted on 2019-10-08, 14:44 authored by Lina C. Harfouche, Clément Brandel, Yohann Cartigny, Joop H. ter Horst, Gérard Coquerel, Samuel PetitThe
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 (β = 2.3)
remains clear for almost 1 h at 20 mL scale, revealing a slow nucleation
rate. Seeding the supersaturated solution with the pure enantiomer triggered its crystallization
both isothermal and polythermic modes of PC were successfully implemented.
Alongside the reported case of diprophylline, this study opens opportunities
to broaden the application of PC toward slowly crystallizing racemic
compounds.