作为有机合成中间体,用于构建药物分子骨架;可通过官能团转化(如羧酸→酰胺→酮羰基→双键等)实现多种化学转化。
医药
合成路线1(原料:DL-哌啶酸、碳酸钾、二碳酸二叔丁酯)
- 步骤:将DL-哌啶酸(13g,100mmol)、碳酸钾(55.2g,400mmol)、二碳酸二叔丁酯(28.4g,130mmol)溶于丙酮(30mL)和水(100μL)混合溶剂中,室温搅拌过夜;反应完成后用1N盐酸水溶液调节pH至3,乙酸乙酯(350mL)萃取;有机相依次用水(200mL)、饱和食盐水(200mL)洗涤,无水硫酸钠干燥,减压浓缩;固体用己烷研磨得目标产物。
- 收率:99%(22.7g)
- 表征数据:1H NMR(CDCl3,δ ppm):9.3(宽单峰,1H),4.84(宽双峰,1H),3.94(多重峰,1H),2.93(多重峰,1H),2.22(多重峰,1H),1.67(多重峰,3H),1.45(多重峰,11H)
- 参考文献:[1] Tetrahedron Letters, 1996, 37(20), 3441-3444;[2] Patent: WO2004/14902, 2004, A2(Page 45);[3] Organic Letters, 2013, 15(4), 824-827;[4] Journal of Organic Chemistry, 2005, 70(15), 5954-5963;[5] Journal of Organic Chemistry, 1999, 64(6), 1993-2002;[6] Journal of Organic Chemistry, 2002, 67(13), 4414-4422;[7] Journal of Medicinal Chemistry, 2009, 52(21), 6672-6684;[8] Journal of Organic Chemistry, 1990, 55(2), 738-741;[9] Bioorganic and Medicinal Chemistry, 2018, 26(20), 5547-5554;[10] Journal of Medicinal Chemistry, 1992, 35(23), 4334-4343;[11] Patent: US5571832, 1996, A;[12] European Journal of Organic Chemistry, 1998(6), 1143-1153;[13] Bioorganic and Medicinal Chemistry Letters, 2004, 14(15), 4013-4017;[14] Patent: US2002/42377, 2002, A1;[15] Patent: US2002/52410, 2002, A1;[16] Patent: EP1593681, 2005, A1(Page/Column 43);[17] Bioorganic and Medicinal Chemistry Letters, 2011, 21(6), 1832-1837;[18] Chemical Communications, 2017, 53(74), 10299-10302