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Demonstration of Lossen Rearrangement on Kilogram Scale

有机合成与工艺文献分享 2025-02-26 07:23
文章摘要
本文探讨了在药物候选物1的合成过程中，如何通过Lossen重排替代Curtius重排以提高工艺安全性。药物1作为葡萄糖神经酰胺合成酶的抑制剂，最初通过酰基叠氮的形成和Curtius重排合成，但这一过程存在安全隐患。研究开发了一种更安全的合成方法，通过CDI介导的Lossen重排，在较温和的条件下将羟基酰胺转化为异氰酸酯，减少了危险中间体的使用。此方法在公斤级规模上成功实施，显著降低了工艺风险。
Demonstration of Lossen Rearrangement on Kilogram Scale
查看文献： Process Development of a GCS Inhibitor Including Demonstration of Lossen Rearrangement on Kilogram Scale
查看期刊： Organic Process Research & Development
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