4-(2,4-二氟苯甲酰基)-哌啶的合成研究

The Synthesis of 4-(2,4-Difluorobenzoyl)-Piperidine

利培酮作为临床上用于治疗精神分裂症最常用的药物之一,其原料药的合成技术研究具有十分广阔的前景。本文提供了一种利培酮的中间体——4-(2,4-二氟苯甲酰基)-哌啶的制备方法,以4-哌啶甲醛和2,4-二氟苯肼为原料,二甲基亚砜为溶剂,氯化铜(CuCl2)为催化剂,过氧化叔丁醇(TBHP)为氧化剂,经自由基偶联反应制备4-(2,4-二氟苯甲酰基)-哌啶,并通过核磁等表征确认结构。该方法实验步骤简单,反应条件温和,合成成本低,收率高(83.1%),为该化合物的合成提供了一种新思路。

Risperidone is one of the most commonly used drugs for the treatment of schizophrenia in clinic.The research on the synthesis technology of risperidone API has a very broad prospect.This paper provides a preparation method of 4-(2,4-difluorobenzoyl)-piperidine,an intermediate of risperidone.4-(2,4-difluorobenzoyl)-piperidine was prepared by free radical coupling reaction with 4-piperidine formaldehyde and 2,4-difluorophenylhydrazine as raw materials,DMSO as solvent,CuCl2as catalyst and TBHP as oxidant,and the structure was confirmed by NMR and other characterization.The method has the advantages of simple experimental steps,mild reaction conditions,low synthesis cost and high yield(83.1%),which provides a new idea for the synthesis of the compound.