作为医药中间体,用于合成相关药物分子(具体药物未明确提及)
医药中间体
路线1:硼烷还原法
- 原料:2-溴-5-甲氧基苯甲酸(2.25g,9.7mmol)
- 步骤:将2-溴-5-甲氧基苯甲酸溶于THF(10mL)中并冷却至0℃;在THF(48mL,48mmol)中加入1M硼烷并温热至室温;反应完成后,将反应缓慢倒入冰和饱和碳酸氢钠水溶液中;用乙酸乙酯萃取,用水和饱和碳酸氢钠水溶液洗涤有机层;用硫酸钠干燥,过滤并真空浓缩,得到目标产物。
- 条件:With borane In tetrahydrofuran at 0 - 20℃
- 收率:100%
- 参考文献:[1] Patent: WO2004/9578, 2004, A2. Location in patent: Page 31 [2] Journal of Organic Chemistry, 2005, vol. 70, # 2, p. 756 - 759 [3] European Journal of Medicinal Chemistry, 2015, vol. 94, p. 149 - 162 [4] Journal of Organic Chemistry, 1993, vol. 58, # 17, p. 4579 - 4583 [5] Bioorganic and Medicinal Chemistry Letters, 2004, vol. 14, # 17, p. 4511 - 4514 [6] Patent: US2004/77853, 2004, A1. Location in patent: Page 25 [7] Patent: WO2007/129119, 2007, A1. Location in patent: Page/Page column 43 [8] Patent: WO2009/10783, 2009, A1. Location in patent: Page/Page column 45 [9] Patent: US6353110, 2002, B1. Location in patent: Page column 25 [10] Journal of Medicinal Chemistry, 2006, vol. 49, # 15, p. 4721 - 4736 [11] Journal of Organic Chemistry, 1999, vol. 64, # 26, p. 9658 - 9667 [12] Journal of Medicinal Chemistry, 2006, vol. 49, # 15, p. 4447 - 4450 [13] Tetrahedron, 1998, vol. 54, # 37, p. 11209 - 11234 [14] Patent: WO2004/48314, 2004, A1. Location in patent: Page 50-52 [15] Patent: US2003/87891, 2003, A1 [16] Patent: US5807897, 1998, A [17] Patent: EP883599, 2002, B1 [18] Bioorganic and Medicinal Chemistry Letters, 2009, vol. 19, # 12, p. 3193 - 3195 [19] Journal of the American Chemical Society, 2011, vol. 133, # 20, p. 7916 - 7925 [20] Chemistry - An Asian Journal, 2018, vol. 13, # 17, p. 2401 - 2404
路线2:氢化铝锂还原法
- 原料:2-溴-5-甲氧基苯甲酸甲酯(5.0g,20.4mmol)
- 步骤:向搅拌的氢化铝锂(1.2g,30.6mmol)的无水四氢呋喃(40ml)悬浮液中滴加2-溴-5-甲氧基苯甲酸甲酯的无水四氢呋喃(80ml)溶液;在氮气下在0℃下将反应混合物搅拌1小时;向反应混合物中加入硫酸钠十水合物和氟化钾;将所得混合物在室温下搅拌1小时,并通过硅藻土垫过滤;浓缩滤液,得到粗产物,用硅胶柱色谱法纯化,用己烷和乙酸乙酯(10:1,8:1,6:1)梯度洗脱,得到目标产物。
- 条件:With lithium aluminium tetrahydride In tetrahydrofuran at 0℃; for 1 h
- 收率:94.9%
- 参考文献:[1] Tetrahedron, 1998, vol. 54, # 37, p. 11209 - 11234 [2] Patent: US2003/208079, 2003, A1. Location in patent: Page/Page column 8 [3] Patent: US6514964, 2003, B1
路线3:N-溴代琥珀酰亚胺溴代法
- 原料:3-甲氧基苄醇(13.82g,0.1mol)
- 步骤:使3-甲氧基苄醇和NBS(19.58g,0.11mol)在乙腈(250mL)中在室温下反应3小时;除去溶剂,将得到的物质在二氯甲烷(250mL)中浆化,过滤除去不溶的琥珀酰亚胺副产物;通过色谱法(20%EtOAc-己烷)纯化粗物质,得到目标产物。
- 条件:With N-Bromosuccinimide In acetonitrile at 20℃; for 3 h
- 收率:81%
- 参考文献:[1] Dalton Transactions, 2013, vol. 42, # 2, p. 355 - 358 [2] Patent: WO2005/82880, 2005, A1. Location in patent: Page/Page column 16 [3] Chemistry - A European Journal, 2011, vol. 17, # 39, p. 10906 - 10915