依福地平中间体的合成工艺改进

Improvement in the Synthesis of Efonidipine Intermediate

以N-苄基苯胺为原料,经亲核取代、酯胺交换和氨基取代3步反应得到依福地平关键中间体3-氨基-2-丁烯酸-2-(N-苄基-N-苯基)氨基乙酯(氨基片段)。酯交换一步采用碱性催化剂替代原工艺中酸性催化剂;氨基取代一步添加ZSM-5分子筛催化,并采用不锈钢曝气头取代原工艺中导气管。新工艺缩短了反应的时间,降低了氨气的用量,提高了反应收率。改进后的工艺,总收率提高至72.4%,较原工艺提高了9.0%,生产成本降低,操作简便易行,适合工业化生产。

The key intermediate of [2-（N-benzyl-N-phenyl）amin]ethyl-3-amino-2-butenoat was obtained from N-benzeneimine via the nucleophilic substitution, transesterification and amino substitution. In the transesterification step, the alkaline catalyst was used to replace the acidic catalyst in the original process, the ZSM-5 molecular sieve catalysis and stainless steel aerator was added In the step of amino substitution. The new process shortens the reaction time, reduces the amount of ammonia, and improves the reaction yield. The total yield is increased to 72.4%, 9.0% higher than the original process. The production cost is reduced, the operation is simple and easy, and the method is suitable for industrial production.