(3-溴丙氧基)-叔丁基二甲基硅烷是一种制备哌啶酰羰基磺酸盐的试剂,作为一种新型的抗高脂血症药物,通过接头蛋白常染色体隐性高胆固醇血症上调ldl受体。
医药
合成路线 1(1. 合成:89031-84-5)
产率:93%
合成条件:at 20℃; for 3 h; Inert atmosphere
实验步骤:实施例C:3-(3-(2,5-二氧代-4-(3,4,5-三甲氧基苯基)-2,5-二氢-1H-吡咯-3-基)-1H-吲哚-1-基) 2-氨基-4-甲基戊酸丙酯3-溴丙氧基 - 叔丁基二甲基硅烷Galka等人的改进方法。 (J.Lab.Comp.Rad.2005,48(11):797-809)用于制备标题化合物。 将3-溴丙醇(39.1毫摩尔; 5.43克),叔丁基二甲基甲硅烷基氯(43.2毫摩尔; 6.47克)和咪唑(46.7毫摩尔; 3.20克)的混合物在室温下在惰性气体下搅拌3小时。 将反应用水淬灭,用二乙醚萃取,将有机层用MgSO 4干燥,过滤并浓缩。 通过柱色谱(PE)实现纯化,得到标题化合物(36.4毫摩尔; 93%)。 1H NMR(300MHz,CDCl3)3.73(t; 3J = 5.7Hz; 2H; CH2O); 3.51(t; 3J = 6.4Hz; 2H; CH2Br); 2.02(q; 3J = 5.7Hz; 3J = 6.4Hz; 2H; CH2CH2CH2); 0.89(s; 9H; C(CH3)3); 0.06(s; 6H; 2xCH3)。
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合成路线 2(2. 合成:89031-84-5)
产率:92%
合成条件:With 1H-imidazole In dichloromethane at 20℃; for 0.17 h; Cooling with ice
实验步骤:将3-溴丙醇(4.14g,30mmol)加入到DCM(50mL)中,加入咪唑(2.5g,30mmol),在冰下搅拌10分钟,加入TBDMS(4.5g,30mmol)并且 在室温下继续反应。 第二天,DCM(50mL)(30mL X3),经无水硫酸镁干燥并浓缩,得到7g无色油,产率92%。
参考文献:
- [1] Patent: CN107098886, 2017, A. Location in patent: Paragraph 0501; 0502