地尔硫中间体的合成工艺研究

Study on the synthetic technology of the intermediate of diltiazem

目的合成地尔硫的重要中间体d-cis-2-(4-甲氧基苯基)-3-羟基-2,3-二氢-1,5-苯并硫氮杂-4(5H)-酮。方法以对甲氧基苯甲醛为原料,经Darzens缩合、硫烷基化、水解、拆分、环合5步反应得到地尔硫的重要手性中间体。结果与结论目标化合物的总收率为34.0%,该法提高了收率,降低了成本,简化了操作,适于工业化生产。

Aim To synthesize the key intermediate d-cis-2- （4-methoxyphenyl） -3-hydroxyl-2,3-dihydro-1,5- benzothiazepin-4 （5H）-one of diltiazem. Methods The intermediate was prepared from p-methoxybenzaldehyde through 5 steps like Darzens condensation, S-alkylation, hydrolysis, resolution and cyclization. Results and conclusion The total yield of the process was 34. 0 %. This synthetic process is suitable for large scale preparation with a higher yield,lower cost and simplified operation.