2,4,5-三氟苯乙酸合成工艺研究  

Study on Synthesis Process of 2,4,5-Trifluorophenylacetic Acid

作　　者：王建华 郎学坤 肖旺钏[1,2,3] 陈志航 WANG Jianhua;LANG Xuekun;XIAO Wangchuan;CHEN Zhihang(College of Resources and Chemical Engineering,Sanming University,Sanming,Fujian 365004,China;Sanming Institute of Fluorochemical Industry,Sanming,Fujian 365004,China;Shanghai-Sanming Engineering Research Center of Green Fluoropharmaceutical Technology,Sanming,Fujian 365004,China)

机构地区：[1]三明学院资源与化工学院,福建三明365004 [2]三明市氟化工产业技术研究院,福建三明365004 [3]沪明绿色氟代制药工程技术研究中心,福建三明365004

出　　处：《浙江化工》2025年第2期21-25,共5页Zhejiang Chemical Industry

基　　金：福建省科技计划项目(2022L3045,2022H6035)。

摘　　要：目的:开发出工艺操作简单、绿色环保、实用性强的西他列汀重要中间体2,4,5-三氟苯乙酸的合成工艺路线,以期获得较优的工艺参数。方法:以2-(2,5-二氰基-3,4,6-三氟苯基)氰乙酸甲酯为原料,经水解和脱羧反应得到2,4,5-三氟苯乙酸。考察催化剂用量、酸的浓度、溶剂和催化剂回收等因素对反应的影响。结果:在酸性条件的水解工艺中,当硫酸浓度为60%,路易斯酸催化剂三氯化铁的用量为2-(2,5-二氰基-3,4,6-三氟苯基)氰乙酸甲酯质量的20%时,水解产物得率达88%。当以铜粉为催化剂进行脱羧反应时,用量为(2,5-二羧基-3,4,6-三氟)苯乙酸质量的20%时,脱羧产物2,4,5-三氟苯乙酸的最高得率为92%。新铜粉不利于脱羧反应,需进行前处理。回收的铜粉和溶剂可重新用于脱羧反应。结论:该合成工艺路线具有材料易得、反应条件易实现、三废排放少等优点。Objective:To develop a process route for the synthesis of sitagliptin,an important intermediate 2,4,5-trifluorophenylacetic acid,which is simple,environmentally friendly and practical,in order to obtain better process parameters.Methods:2,4,5-trifluorophenylacetic acid was obtained by hydrolysis and decarboxylation of methyl 2-(2,5-dicyano-3,4,6-trifluorophenyl)cyanoacetate as raw material.The effects of catalyst dosage, acid concentration, solvent and catalyst recovery on the reaction were investigated. Results: In the hydrolysis process under acidic conditions, the yield of the hydrolysate was 88% when the concentration of sulfuric acid was 60% and the amount of ferric chloride in the Lewis acid catalyst was 20% of the mass of 2-(2,5-dicyano-3,4,6-trifluorophenyl)methyl cyanoacetate. When copper powder is used as a catalyst for decarboxylation, the highest yield of 2,4,5-trifluorophenylacetic acid is 92% when the dosage is 20% of the mass of (2,5-dicarboxyl-3,4,6-trifluorophenylacetic acid). The new copper powder is not conducive to decarboxylation reaction and needs to be pretreated. The recovered copper powder and solvent can be reused for decarboxylation reactions. Conclusion: The synthesis process route has the advantages of easy availability of materials, easy realization of reaction conditions, and less emission of three wastes.

关 键 词：2 4 5-三氟苯乙酸 西他列汀 水解 脱羧 

分 类 号：TQ460.31[化学工程—制药化工]