3-氯甲基-1,2,4-三唑啉-5-酮合成工艺研究

3-氯甲基-1,2,4-三唑啉-5-酮是生产合成阿瑞吡坦、福沙吡坦等药物的重要中间体。为简化工艺路线,降低成本,提高收率。本文的合成工艺采用的原料廉价易得,减少反应步骤,操作简单,避免了中间产物降解,各操作反应条件温和,优化了生产工艺,降低了成本等特点。其中醇解与环合两步反应合并为一锅法来完成,减少了溶剂用量,简化了操作步骤,反应的产物可以达到85.39%的收率,HPLC检测纯度达99%以上,含量达99%以上,取得良好的效果,更加适合于工业生产。

The Research of the Preparation Process of 3-Chloromethyl-1,2,4-triazolin-5-one

3 - Chloromethyl - 1,2,4 - triazolin - 5 - one was one kind of material that was used in the production Aprepitant or Fosaprepitant. In order to simplify process, the cost was reduced and the yield was enhanced, using cheap materials and reduced reaction steps comparing with other process reported by papers. The operations were classical and simple. The intermediate was avoided degradation. The process was optimized and the costs were reduced. Especially, the alcoholysis and cyclization were combined to a one - pot reaction, which reduced the amount of solvent and reaction steps. The yield of one - pot reaction reached to 85.39%. The HPLC purity reached to 99%, the content reached to 99% , and the material was suitable for industrial production.