文献类型：期刊文献

中文题名：硫酸羟氯喹的工艺优化

英文题名：Improved Synthetic Process of Hydroxychloroquine Sulfate

作者：裘雯梅[1];徐小丽[1];陈春燕[1];马立荣[1];赵建宏[1]

机构：[1]华东理工大学药学院,华东理工-中西三维绿色制药联合研究中心,上海200237

年份：2020

卷号：51

期号：5

起止页码：591

中文期刊名：中国医药工业杂志

外文期刊名：Chinese Journal of Pharmaceuticals

收录：CSTPCD;;北大核心:【北大核心2017】；CSCD:【CSCD_E2019_2020】；

语种：中文

中文关键词：硫酸羟氯喹;类风湿关节炎;合成;工艺优化

外文关键词：hydroxychloroquine sulfate;rheumatoid arthritis;synthesis;process improvement

摘要：本研究改进了硫酸羟氯喹(1)的合成工艺。以碳酸钾为缚酸剂,4,7-二氯喹啉(3)和5-[N-乙基-N-(2-羟乙基)-氨基]-2-戊胺(4)在正丁醇中回流反应得到羟氯喹(2),在2的正丁醇溶液中直接滴加硫酸成盐得到1,乙醇重结晶后纯度99.06%。改进后的工艺步骤少,操作简便。正丁醇作为溶剂有效地避免3因升华而损失,同时碳酸钾作缚酸剂减少了杂质4-[2-(5-羟基乙胺基)戊基]氨基-7-氯喹啉(5)和N-[2-[(7-氯喹啉-4-基)氧基]乙基]-N-乙基戊烷-1,4-二胺(6)的产生,使得总收率从39%提高至69%(以3计)。
The synthetic process of hydroxychloroquine sulfate(1) was improved. 4,7-Dichloroquinoline(3) and 5-(N-ethyl-N-2-hydroxyethylamino)-2-pentylamine(4) were refluxed in n-butanol with potassium carbonate as the acid binding agent to give hydroxychloroquine(2). Sulfuric acid was directly added dropwise to the n-butanol solution of 2 to obtain 1 with a purity of 99.06% after recrystallization with EtOH. The improved process involved fewer steps and was easy to operate. Using n-butanol as a solvent would effectively avoid the loss of 3 due to sublimation, and using potassium carbonate as an acid-binding agent could decrease the formation of impurities 4-[2-(5-hydroxyethylamino)-pentyl]amino-7-chloroquinoline(5) and N-[2-[(7-chloroquinoline-4-yl)oxy]ethyl]-N-ethylpentane-1,4-diamine(6). The total yield increased from 39% to 69%(based on 3).