厄他培南钠的合成研究

摘要

Objective The development of a scaleable process for the manufacture of ertapenem involved the synthesis of side chain is described. Methods Beginning with N-PNZ-4-hydroxy- L-proline, an one-pot process of side chain via thiolactone was demonstrated. A telescoped sequence of condensation, deprotection and the formation of sodium salt generates the title compound. Results The key intermediates and ertapenem were characterized by IR, 'HNMR and MS. The process has been successfully implemented to prepare several kilogram batches of the target compound in 40% overall yield and 99.2% area purity. Conclusion A pilot-plant suitable process of ertapenem with high yield and amenable to industrialization was provided.%目的 开发目标化合物及其侧链放大工艺。方法 以L-PNZ-羟脯为原料采用“一锅煮”工艺，通过硫内酯中间体制备厄他培南侧链，再经缩合、脱保护成盐合成目标化合物。结果 目标化合物及中间体经红外光谱、核磁共振氢谱和质谱确证化学结构，厄他培南放大工艺总收率40％(以MAP计)，纯度99.2％。结论 该合成工艺为中试规模，收率高，易于实现产业化。