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 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. 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.

中文翻译：

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迈向手性拆分新方法：加压 CO2 辅助优先共结晶


我们在此报道了压缩二氧化碳辅助下的优先共结晶过程的首次发生。我们的研究重点是奈非拉西坦-扁桃酸聚集体形成系统。在所谓的 GAS 工艺中，使用压缩 CO 作为反溶剂，丙酮、乙酸乙酯或异丁醇作为起始溶液的溶剂，成功结晶了共晶聚集体。然后，我们专注于丙酮，成功地在压缩 CO 的支持下进行优先共结晶。该工艺设计的关键步骤是调整设置，以允许在反应器内引入对映体纯晶种。基于晶种环的使用，我们测试了几种晶种配置，以通过两种对映体在反应器的两个不同区域同时结晶来增强对映体分离。