3-氟-4-氯苯硼酸的合成工艺优化

摘要

(4-Chloro-3-fluorophenyl)boronic acid was synthesized from 5-bromo-2-chloroaniline via diazotization to give 4-bromo-1-chloro-2-fluorobenzene which was subjected to Grignard exchange with EtMgBr, reaction with trimethyl borate, and hydrolysis with a yield about 60% and an HPLC purity of 99% under the optimal conditions. The effects of the trial in grignard exchanging method was compared with that using grignard reagent and tributyl lithium. The effects of boronation reagent,reaction temperature,molar ratio of raw materials on the yield of target product were investigated.The condition of grignard exchanging method is mild and suitable for industrial scale production without using ultra-low temperature and other more severe conditions.%以2-氯-5-溴苯胺为起始原料，经重氮化反应得到2-氯-5-溴氟苯，再与乙基溴化镁进行格式交换后与硼酸三甲酯作用，水解得到3-氟-4-氯苯硼酸。实验过程中将格式试剂法、三丁基锂法与格氏试剂交换法作对比，并对格氏试剂交换法的过程条件如硼化试剂、反应温度、反应原料配比进行了优化，在最优条件下总收率约60%，纯度99%。此过程采用的是较温和的格氏试剂交换法，无需用到超低温等较苛刻的条件，适于工业放大生产。