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Process Development of a Guareschi−Thorpe Reaction

有机合成与工艺文献分享 2025-09-01 07:25
文章摘要
背景：ACT-334441是一种合成鞘氨醇1-磷酸1受体激动剂，用于治疗自身免疫性疾病。研究目的：针对Negishi偶联反应在放大生产中存在的高稀释度、高成本及锌废物处理等问题，开发基于Guareschi−Thorpe反应的替代合成工艺。结论：通过优化反应条件（如改用THF/KOtBu体系、替换氯化试剂为苯基膦酰二氯），成功开发出包含18个化学步骤、10个分离中间体的可行工艺路线，有效解决了放大生产中的关键问题。
Process Development of a Guareschi−Thorpe Reaction
查看文献： Practical Synthesis of a S1P Receptor 1 Agonist via a Guareschi–Thorpe Reaction
查看期刊： Organic Process Research & Development
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