吲达帕胺的合成工艺研究  

Study on Synthesis Technology of Indapamide

作　　者：俞军 李庆 张清玉 汪宏冠 叶陆飞 YU Jun;LI Qing;ZHANG Qingyu;WANG Hongguan;YE Lufei(Zhe Jiang Xinan Chemical Industrial Group Co.,Ltd.,Jiande,Zhejiang 311600;Zhejiang Leide Organosilicon Material Co.,Ltd.,Hangzhou 311607)

机构地区：[1]浙江新安化工集团股份有限公司,浙江建德311600 [2]浙江励德有机硅材料有限公司,杭州311607

出　　处：《化工生产与技术》2024年第4期8-11,I0002,I0003,共6页Chemical Production and Technology

摘　　要：针对吲达帕胺合成步骤繁琐及收率不高的问题,本文以2-甲基吲哚啉和对氯苯甲酸为主要原料,依次经过Zn/AcOH催化加氢、亲核缩合反应、成盐与离子交换及精制等方法,研究了合成过程中反应温度、反应时间、缚酸剂及溶剂对吲达帕胺收率的影响。结果表明在吲达帕胺粗品合成时,当反应时间为24h,反应温度在-5~0℃,三乙胺作为缚酸剂时,收率可达88.2%;吲达帕胺粗品提纯阶段利用异丙醇与水体积比为3∶2混合溶剂,可得到收率92.8%、纯度99.5%的吲达帕胺产品。该方法具有步骤简单、条件温和、成本较低的优点,适宜工业化生产。To address the issues of cumbersome synthesis steps and low yield in the synthesis of indapamide,this article used 2-methylindoline and p-chlorobenzenesulfonic acid as the main raw materials,and studied the effects of reaction temperature,reaction time,acid scavenger,and solvent on the yield of indapamide through Zn/AcOH catalytic hydrogenation、nucleophilic condensation reaction,salt formation and ion exchange,and purification methods.The results showed that when the reaction time was 24 h,the reaction temperature was-5~0℃,and triethylamine was used as the acid scavenger during the synthesis of crude indapamide,the yield could reach 88.2%.In the purification stage of crude indapamide,using a mixed solvent of volume ratio of isopropyl alcohol to water of 3:2,indapamide products with a yield of 92.8%and a purity of 99.5%could be obtained.This method has the advantages of simple steps,mild conditions and lower cost,and is suitable for industrial production.

关 键 词：吲达帕胺 2-甲基吲哚啉 对氯苯甲酸 

分 类 号：TQ463.53[化学工程—制药化工]