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24 h,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.
Abstract
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.
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