Towards a new approach in chiral resolution: Pressurized-CO2 assisted preferential cocrystallization.

We here report the first occurrence of a preferential cocrystallization process assisted by compressed carbon dioxide. Our study focuses on the Nefiracetam-Mandelic acid conglomerate forming system. The cocrystal conglomerate was successfully crystallized using compressed CO 2 as antisolvent, and acetone, ethyl acetate, or isobutanol as solvents for starting solutions in the so-called GAS process. We then focus on acetone to successfully perform preferential cocrystallization supported by compressed CO 2. A critical step in the design of the process is the adaptation of the set-up to allow the introduction of enantiopure seeding inside the reactor. Based on the use of seeded rings, we test several seeding configurations to enhance enantioseparation through the simultaneous crystallization of both enantiomers in two different areas of the reactor. [Display omitted] • Successful formation of nefiracetam-mandelic acid cocrystal conglomerate using GAS. • Seeding of a pressurized vessel to target the growth of a specific enantiomer. • First proof of concept of preferential cocrystallization assisted by GAS. • Increase of the enantiopurity by seeding two different areas of the vessel. [ABSTRACT FROM AUTHOR]