路线1:1-(4-溴苯基)吡咯烷(化合物0601-155)的合成
- 反应物:4-溴苯胺(1g,5.81mmol)、Cs₂CO₃(5.68g,17.44mmol)、1,4-二溴丁烷(1.88g,8.72mmol)
- 溶剂:DMF(20mL)
- 条件:60℃搅拌反应过夜
- 后处理:冷却至室温,用水(200mL)稀释,乙酸乙酯(2×100mL)萃取;合并有机层,依次用水(3×100mL)和盐水(100mL)洗涤,无水Na₂SO₄干燥;减压浓缩
- 纯化:硅胶柱色谱(洗脱剂:石油醚)
- 产物:目标化合物0601-155(720mg,收率46%),无色油状物
- 表征:LCMS:226 [M + 1]+;¹H NMR(400MHz,DMSO-d₆)δ1.94(t,J=6.4Hz,4H),3.18(t,J=6.4Hz,4H),6.47(d,J=9.2Hz,2H),7.27(d,J=9.2Hz,2H)
- 参考文献:
[1] Journal of the American Chemical Society, 2014, vol. 136, # 33, p. 11602 - 11605
[2] Journal of Organic Chemistry, 2006, vol. 71, # 1, p. 135 - 141
[3] Patent: WO2011/130628, 2011, A1. Location in patent: Page/Page column 221
[4] Patent: US2013/102595, 2013, A1. Location in patent: Paragraph 0550