化学合成;S-(-)-N,N-二甲基-3-羟基-3-(2-噻吩)丙胺是盐酸度洛西汀重要中间体,可用于医药研发和实验室研究;度洛西汀中间体。
医药
合成路线 1(132335-44-5)
- 步骤:将(R,R)-Cl₂((R)-己基BINAP)((R)-DAIPEN)、2-丙醇、1.0M叔丁氧基钾的2-丙醇溶液和3-(N,N-二甲基氨基)-1-(2-噻吩基)-1-丙酮依次加入玻璃高压釜,经脱气、氩气置换后通氢气,28℃搅拌6小时,浓缩后加庚烷抽滤,减压干燥得目标物。
- 条件:With potassium tert -butylate; hydrogen In isopropyl alcohol; tert -butyl alcohol at 28℃; for 6 h;
- 收率:80%
- 参考文献:[1] Patent: EP1506965, 2005, A1; [2] Angewandte Chemie (International ed. in English), 2004, vol. 43, #21; [3] Chemistry - A European Journal, 2011, vol. 17, #28; [4] Patent: US8426178, 2013, B2; [5] Chemical Communications, 2015, vol. 51, #61; [6] Journal of Molecular Catalysis B: Enzymatic, 2015, vol. 122; [7] Patent: KR2015/43955, 2015, A
合成路线 2(132335-44-5)
- 步骤:将外消旋混合物溶于甲苯和甲醇,加入S-扁桃酸,加热至95℃保持1.5小时,冷却后过滤沉淀,用甲苯洗涤,真空干燥后加2N氢氧化钠溶解,MTBE萃取,合并有机物干燥浓缩得目标物。
- 条件:With (S)-Mandelic acid In methanol; toluene at 20 - 95℃; for 1.50 h;
- 收率:34%
- 参考文献:[1] Bioorganic Chemistry, 2016, vol. 65; [2] Patent: CN105566284, 2016, A; [3] Organic Process Research and Development, 2006, vol. 10, #5; [4] Patent: CN104803968, 2017, B; [5] Patent: CN104829587, 2017, B; [6] Patent: CN107488163, 2017, A