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Classical Resolution for Atropisomerically Pure Intermediate

有机合成与工艺文献分享 2025-10-10 06:56
文章摘要
本文研究了通过经典手性拆分方法分离构象异构体1的可行性。背景是已获得rac-1的快速合成路线，研究目的是评估不同拆分剂对构象异构体的分离效果。实验发现(+)-DBTA能选择性拆分M-1异构体，形成三组分共晶溶剂化物，且(+)-DBTA浓度需超过200 mg/mL才能热力学优先结晶。研究结论表明提高(+)-DBTA浓度可提升M/P比例并抑制rac-1结晶，该工艺已成功应用于500公斤级生产，为合成KRAS G12C抑制剂sotorasib提供关键中间体。
Classical Resolution for Atropisomerically Pure Intermediate
查看文献： Axial Chirality in the Sotorasib Drug Substance, Part 1: Development of a Classical Resolution to Prepare an Atropisomerically Pure Sotorasib Intermediate
查看期刊：Organic Process Research & Development
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