化学合成。
医药中间体
合成路线 1（1. 合成：26510-95-2）
产率：90%
合成条件：Stage #1: With sodium hydride In toluene; mineral oil at 0 - 20℃; for 2 h; Stage #2: Reflux
实验步骤：在0℃下，向NaH（80g，60％矿物油分散体，2mol）的甲苯（1.2L）溶液中加入碳酸二乙酯（295g，2.50mol）。 在室温下搅拌2小时后，将混合物在回流下滴加到化合物15-1（99g，0.50mol）的甲苯（400mL）溶液中。 回流过夜后，将反应混合物冷却至室温并依次用HOAc（140mL）和水溶液处理。 HCl（2M，864mL）。 将得到的混合物用EtOAc（400mL×3）萃取，并将合并的有机萃取液用水（500mL×4）和盐水（200mL×2）洗涤，并用无水Na 2 SO 4干燥。 除去溶剂，将残余物真空干燥，得到化合物15-2（122g，90％收率），为油状物。 LC-MS（ESI）：m / z 271.0 [M + H] +。
参考文献：
- [1] European Journal of Organic Chemistry, 2017, vol. 2017, # 31, p. 4543 - 4547 [2] Patent: WO2012/58125, 2012, A1. Location in patent: Page/Page column 147 [3] Beilstein Journal of Organic Chemistry, 2017, vol. 13, p. 1950 - 1956 [4] Archiv der Pharmazie, 2003, vol. 336, # 3, p. 181 - 190 [5] Molecules, 2004, vol. 9, # 3, p. 135 - 157 [6] Farmaco, Edizione Scientifica, 1985, vol. 40, # 4, p. 272 - 284 [7] Journal of the American Chemical Society, 2018, vol. 140, # 5, p. 1622 - 1626 [8] Patent: WO2014/147611, 2014, A1. Location in patent: Page/Page column 56; 57 [9] Organic Letters, 2014, vol. 16, # 19, p. 5152 - 5155 [10] Patent: WO2015/35027, 2015, A1. Location in patent: Page/Page column 122 [11] Patent: WO2005/40110, 2005, A1. Location in patent: Page/Page column 255 [12] Patent: US6329408, 2001, B1 [13] Polymer, 2010, vol. 51, # 26, p. 6107 - 6114 [14] Angewandte Chemie - International Edition, 2011, vol. 50, # 32, p. 7304 - 7307 [15] Patent: US2011/263559, 2011, A1. Location in patent: Page/Page column 51 [16] Patent: WO2012/3164, 2012, A1. Location in patent: Page/Page column 21 [17] Angewandte Chemie - International Edition, 2012, vol. 51, # 34, p. 8661 - 8664 [18] Journal of the American Chemical Society, 2013, vol. 135, # 32, p. 11692 - 11695 [19] Organic Process Research and Development, 2006, vol. 10, # 5, p. 899 - 904 [20] Organic Letters, 2016, vol. 18, # 20, p. 5408 - 5411 [21] Organic Letters, 2017, vol. 19, # 23, p. 6344 - 6347 [22] Organic and Biomolecular Chemistry, 2018, vol. 16, # 25, p. 4683 - 4687 [23] RSC Advances, 2018, vol. 8, # 53, p. 30201 - 30206
