磷酸哌喹杂质7G氯G4G羟基喹啉合成研究

Research on the synthesis of impurity 7-chloro-4-hydroxyquinoline in piperaquine phosphate

报道了磷酸哌喹生产过程中产生的杂质——7-氯-4-羟基喹啉(化合物2)的合成方法。以硅油为脱羧剂,7-氯-4-羟基喹啉-3-羧酸(化合物1)的C-3位发生脱羧反应得到化合物2,其结构经1HNMR和MS表征。考察了影响化合物2收率的主要因素,确定适宜反应条件为:硅油为脱羧剂,在190℃下反应20min。在该条件下,化合物2的收率达到96.8%(以化合物1计)。

The synthesis of impurity(compound 2) of piperaquine phosphate was reported.The compound 2 was easily formed through the decarboxylation of the carboxyl group at C-3 position of 7-chloro-4-hydroxyquinoline-3-carboxylic acid(compound 1) by using silicone oil as a deacidification agent.The structures of impurity(compound 2) were confirmed by ~1HNMR and MS.Moreover, the main factors affecting the yield of impurities(compound 2) were investigated, and the appropriate reaction conditions were determined as follows: silicon oil as the decarboxylation agent, reaction at 190℃ for 20min.The yield was up to 96.8%(calculated as compound 1) under this reaction conditions.