特班布林药物关键中间体的合成研究  

Study on Synthesis of Key Intermediates of Tirbanibulin

作　　者：刘加艳 任宇鹏 LIU Jia-yan;REN Yu-peng(Henan Technical Institute,Henan Zhengzhou 450042,China)

机构地区：[1]河南应用技术职业学院,河南郑州450042

出　　处：《广州化工》2024年第18期36-38,共3页GuangZhou Chemical Industry

基　　金：河南应用技术职业学院校级项目(项目编号:2023-KJ-55)。

摘　　要：创新并优化了一种特班布林关键中间体的合成方法,采用4-[2-(4-溴苯氧基)乙基]吗啉为原料,先与正丁基镁锂试剂发生锂卤交换,再与异丙醇频哪醇硼酸酯发生Miyaura硼酸酯化反应,一锅法合成了该中间体。以产品收率为指标,考察了正丁基锂添加量、原料1添加量、原料2添加量、反应时间对收率的影响;从单因素影响考虑,分别在正丁基锂(2.5 mol/L)添加量45 mL、原料1添加量28 g、原料2添加量20 g、反应时间5.5 h时产物收率最高。A synthesis method for tirbanibulin key intermediates was innovated and optimized.Using 4-[2-(4-bromophenoxy)ethyl]morpholine as the raw material,lithium halide exchange reaction was first carried out with n-butyl lithium,followed by Miyaura borylation reaction with isopropoxyboronic acid pinacol ester.The key intermediate was synthesized in one pot method.The effects of n-butyl lithium addition,material 1 addition,material 2 addition and reaction time were investigated using product yield as an indicator.Considering the single-factor effect,the highest product yield was achieved when the addition amount of n-butyl lithium(2.5 mol/L)was 45 mL,the addition amount of raw material 1 was 28 g,the addition amount of raw material 2 was 20 g,and the reaction time was 5.5 h.

关 键 词：日光性角化病 特班布林 关键中间体 优化合成 

分 类 号：TQ463.5[化学工程—制药化工]