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)。
Abstract
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).
关键词
硫酸羟氯喹 /
类风湿关节炎 /
合成 /
工艺优化
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Key words
hydroxychloroquine sulfate /
rheumatoid arthritis /
synthesis /
process improvement
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参考文献
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