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

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.