雷芬那辛的合成工艺改进研究

Research on the Improved Synthetic Process to Revefenacin

摘要:
目的探索并改进雷芬那辛的合成工艺。
方法以2-苯基苯甲酸(15)和N-Boc-4-羟基哌啶(3)为起始物料，经Curtius重排、亲核取代、氢化还原和缩合4步反应制得雷芬那辛(1)。
结果该工艺的雷芬那辛收率达到63.4%，并经HRMS、¹H NMR和¹³C NMR等确证结构。
结论该工艺具有原料易得、收率高、操作简便、环境友好等优点，适合雷芬那辛工业化生产。

Abstract:
OBJECTIVE To explore and optimize the synthetic process to revefenacin.
METHODS Revefenacin(1) was prepared using 2-phenylbenzoic acid(15) and N-Boc-4-hydroxypiperidine(3) as starting material through 4 steps including Curtius rearrangement, nucleophilic substitution, hydrogenation and condensation.
RESULTS The yield of this synthetic process of revefenacin was 63.4%, and its structure was confirmed by HRMS, ¹H NMR, and ¹³C NMR.
CONCLUSION This synthetic route has the advantages of easily available raw materials, high yield, simple operation, and environmental friendliness, making revefenacin suitable for industrial production.