4-(4-氨基苯氧基-)2-(甲基氨甲酰基)吡啶合成的清洁工艺  

Clean procedure for synthesis [4-(4-Aminop-henoxy) (2-pyrid-yl)]-N-methylcarboxamide in ionic liquid

作　　者：孙超[1] 孙志忠[1] 侯艳君[1] 

机构地区：[1]黑龙江大学化学化工与材料学院,哈尔滨150080

出　　处：《黑龙江大学工程学报》2011年第4期57-61,共5页Journal of Engineering of Heilongjiang University

基　　金：国家自然科学基金项目(20872030)

摘　　要：4-(4-氨基苯氧基)-2-(甲基氨甲酰基)吡啶是合成索拉非尼的重要中间体,它可由Williamson反应合成。以离子液体为溶剂,以NaOH、无水K2CO3为碱,N-甲基-(4-氯-2-吡啶基)甲酰胺和对氨基苯酚为原料,通过Williamson反应合成出目标产物。研究了影响此反应的一些影响因素,如离子液体种类、反应温度、时间、碱等,并在此研究基础上得出了较佳的反应条件为:以[BMIM][BF4]为溶剂,对氨基苯酚与氢氧化钠的摩尔比为1∶1.1,与无水碳酸钾的摩尔比为1∶0.6,反应温度75℃,反应时间4h,在此条件下所得的收率为89%,产品结构由1 H NMR所证实。另外,离子液体至少可循环使用5次,而对收率及纯度无明显影响,有利于环保。[4- （4-Aminophenoxy） （2 pyridyl）] -N-methylcarboxamide is an important intermediate of sorafenib, which can be synthesized via Williamson reactions. The author synthesized the target product from 4-chloro-N-methypiclinamide and 4-Aminophenol via Williamson reaction by use of room-temperature ionic liquid as green solvent, NaOH and K2CO3 as base. Some factors affecting the etherification, such as the type of the ionic liquid, reaction temperature, reaction time and base etc, were studied, and the relatively optimal reaction conditions were worked out： the best solvent is [BMIM] [BF4], the molar ratio of reaction are 4-Aminophenol/NaOH ： 1/1.1 （molar）, 4-Aminophenol/KeCO3 = 1/0.6 （molar）, reaction temperature is 75 ℃, reaction time is 4h. Under the above procedures the yield of resulting could be achieved 89%, and the structural confirmation was done by ^1H NMR. One additional point should be emphasized that the RIL could be reused at least 5 times without noticeably deteriorating the yield and purity of the product. This is beneficial to environmental protection.

关 键 词：4-(4-氨基苯氧基)-2-(甲基氨甲酰基)吡啶 合成 离子液体 

分 类 号：O621.3[理学—有机化学]