碘克沙醇合成工艺研究  

Study on Synthesis Process of Iodixanol

作　　者：陈小林 吕歆 戴佳伟 王宁 代凤丽 夏春年[1] CHEN Xiaolin;LYU Xin;DAI Jiawei;WANG Ning;DAI Fengli;XIA Chunnian(College of Pharmaceutical Science,Zhejiang University of Technology,Hangzhou,Zhejiang 310014,China;Zhejiang Medicines and Health Products Import and Export Co.,Ltd.,Hangzhou,Zhejiang 310003,China;Juxian Pharmaceutical Technology Co.,Ltd.,Taizhou,Zhejiang 317016,China)

机构地区：[1]浙江工业大学药学院,浙江杭州310014 [2]浙江省医药保健品进出口有限责任公司,浙江杭州310003 [3]浙江聚贤医药科技有限公司,浙江台州317016

出　　处：《浙江化工》2023年第7期11-18,共8页Zhejiang Chemical Industry

基　　金：浙江聚贤医药科技有限公司(KYY-HX-20190007)。

摘　　要：碘克沙醇是一种影像诊断用药,通过静脉注射到人体组织和特定器官以增强图像观察效果,适用于锥管内造影、心脑血管造影以及静脉内尿路造影等。本文以间苯二甲酸为起始原料,经微通道连续硝化、酸胺缩合、硝基还原、乙酰化、双羟基化、碘代及二聚共7步反应制备得到目标产物碘克沙醇,反应总收率达31.7%,产物结构经核磁共振氢谱1H NMR、核磁共振碳谱13C NMR和高分辨质谱确证。该合成工艺突出的亮点是原料来源广泛、操作弹性大、反应条件温和、收率较高,可为碘克沙醇工业化生产提供一定的技术支持。Iodixanol is a diagnostic imaging drug,which is injected intravenously into human tissues and specific organs to enhance the image observation effect.It is suitable for intraspinal angiography,cardio-cerebrovascular angiography and intravenously urinary angiography.In this paper,isophthalic acid was used as raw material to synthesize the target product iodixanol through micro-channel continuous nitrification,acid-amine condensation,nitro-reduction,acetylation,dihydroxylation,iodization and dimerization in 7 steps.The total reaction yield reached 31.7%,and the product structure was confirmed by 1H NMR,13C NMR and high resolution mass spectrometry.The outstanding highlights of this synthetic process are the wide range of raw material sources,the high flexibility of operation,mild reaction conditions,high yield,which can provide a certain technical support for the industrial production of iodixanol.

关 键 词：造影剂 碘克沙醇 合成 微通道连续流 新工艺 

分 类 号：TQ460.6[化学工程—制药化工]