特地唑胺的连续流合成工艺研究
Continuous-Flow Process Research and Development of Tedizolid
尹冻安 1郑铭琛 1冼君正 1孙茂林 1程瑞华 1叶金星 1陈浩翔 1邵日新 1骆浩锋1
作者信息
- 1. 广东工业大学生物医药学院，广州 510006
- 折叠
摘要
本文开发了一种汇聚式全连续流动合成特地唑胺的高效工艺路线。该方法集成了亲核开环、环化、Miyaura硼化及Suzuki偶联-水解四步反应，实现了从起始原料到目标产物的连续化制备。针对各反应步骤的关键参数（反应温度、停留时间及物料配比）进行了系统优化，获得了良好的反应性能与操作稳定性。通过精确匹配各反应单元的流速与停留时间，成功构建了多反应模块无缝衔接的连续流体系，避免了溶剂切换及中间体纯化过程。该体系在最优条件下的总停留时间仅为18.4 min，特地唑胺的总分离收率达到72.6%。相比之下，传统间歇工艺的最优总收率为43.3%，且反应时间较长。该研究表明，连续流技术在提高步骤经济性、缩短反应时间及增强工艺可控性方面具有显著优势，为特地唑胺的连续化制备提供了一种具有放大潜力的实用工艺路线。
Abstract
A convergent continuous-flow strategy for the efficient synthesis of tedizolid was developed. The process integrates four sequential transformations, including nucleophilic ring-opening, cyclization, Miyaura borylation, and Suzuki coupling-hydrolysis, enabling the telescoped synthesis of tedizolid from readily available starting materials. Key reaction parameters for each step were systematically optimized under flow conditions, affording high yields and operational stability.By precise matching of flow rates and residence times, the four reaction modules were seamlessly integrated into a fully continuous system, minimizing solvent switching and eliminating intermediate purification steps. Under optimized conditions, the overall residence time was reduced to 18.4 min with an overall isolated yield of 72.6%. In comparison, the corresponding batch process afforded a significantly lower overall yield (43.3%) with longer reaction times.This work demonstrates the advantages of continuous-flow chemistry in improving step economy, process efficiency, and scalability, providing a practical process route with scale-up potential for the continuous-flow preparation of tedizolid.关键词
特地唑胺/连续流合成/汇聚式合成/Miyaura硼化反应/Suzuki偶联-水解反应Key words
Tedizolid/ Continuous-flow synthesis/ Convergent synthesis/ Miyaura borylation/ Suzuki coupling-hydrolysis引用本文复制引用
尹冻安,郑铭琛,冼君正,孙茂林,程瑞华,叶金星,陈浩翔,邵日新,骆浩锋.特地唑胺的连续流合成工艺研究[EB/OL].(2026-05-25)[2026-05-26].http://www.paper.edu.cn/releasepaper/content/202605-106.学科分类
药学/医药卫生理论/医学研究方法/制药化学工业/化学工业概论
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