微波促进合成4-(3-吡啶基)哌啶二盐酸盐  

Microwave-assistde Synthesis of 4-(Pyridine-3-yl)piperidin Dihydrochloride

作　　者：杜会茹[1] DU Hui-ru(Project Supported by Hebei Technological Innovation Center of Chiral Medicine,Pharmaceutical Engineering,Hebei Chemical&Pharmaceutical College,Shijiazhuang 050026,China)

机构地区：[1]河北化工医药职业技术学院制药工程系河北省手性药物技术创新中心,河北石家庄050026

出　　处：《化学试剂》2021年第7期996-999,共4页Chemical Reagents

基　　金：河北省科技厅重点基础研究项目(15962801D);河北省教育厅青年基金资助项目(QN2017053);河北省手性药物技术创新中心开放课题基金资助项目(SG2020221);河北化工医药职业技术学院课题项目(YZ202002)。

摘　　要：以N-叔丁氧羰基-4-哌啶酮为起始原料,经微波促进反应探讨了3-吡啶硼酸、Pd(PPh3)4、H2O、反应温度和反应时间等对叔丁基-4-(3-吡啶基)-5,6-二氢吡啶-1(2H)-羧酸酯反应产率的影响,再经催化氢化、脱去N原子的Boc保护基以及成盐等5步反应合成了标题化合物。中间体叔丁基-4-(3-吡啶基)-5,6-二氢吡啶-1(2H)-羧酸酯最佳反应条件为1.8 mmol 3-吡啶硼酸、5 mmol碳酸钾、0.08 mmol Pd(PPh3)4、15 mL甲苯和2.4 mL H2O、130℃下微波反应20 min,产率达到74.9%。方法具有条件温和、操作简单以及环境友好等优点。A fast and efficient method for the synthesis of tert-butylcarbonyl-1,2,3,6-tetrahydro-4-[(trifluoromethyl) sulfonyloxy] pyridine-1-carboxylates was established based on microwave-assisted reaction.It is found that the amounts of 3-pyridineboronic acid, Pd(PPh3)4,and H2O,the reaction temperature and time duration influenced the synthesis yields significantly.Then, the 4-(pyridine-3-yl)piperidin was synthesized through five steps including the catalytic hydrogenation, deprotection, and salt formation.Tert-butylcarbonyl-1,2,3,6-tetrahydro-4-[(trifluoromethyl) sulfonyloxy] pyridine-1-carboxylateswas was obtained using the optimized condition of 3-pyridineboronic acid(1.8 mmol),K2CO3(5 mmol),Pd(PPh3)4(0.08 mmol),toluene(15 mL),H2O(2.4 mL) at 130 ℃ for 20 min, resulting the isolated yield of 74.9%.The method possesses the advantages of mild synthesis, simple operation and environmental friendliness.

关 键 词：4-(3-吡啶基)哌啶二盐酸盐 3-吡啶硼酸 Suzuki-Miyaura交叉偶联反应 微波促进反应 

分 类 号：O626[理学—有机化学]