- 化学性质
沸点90℃/2kPa,盐酸盐为结晶,熔点218-220℃。
- 眩晕宁的中间体。
医药
合成路线 1(1. 合成:1458-63-5)
产率:93.4%
合成条件:With sodium carbonate In tetrahydrofuran at 66℃; for 15 h;
实验步骤:将四氢呋喃(200ml),哌啶(17.2g,0.2mol),1,3-溴 - 氯丙烷(47.2g,0.3mol),碳酸钠(11.1g,0.105mol)加入到反应烧瓶中,然后回流15小时。 冷却至室温,过滤,浓缩滤液,将残余物溶于2N盐酸中,用乙酸乙酯洗涤两次,将水相调节至pH 10 2NNaOH溶液,并用乙酸乙酯萃取三次,有机相 合并,用无水硫酸镁干燥,过滤,减压浓缩,得到30.2g淡黄色油状物,收率93.4%。
参考文献:
- [1] Patent: CN104447620, 2016, B. Location in patent: Paragraph 0053-0055 [2] Patent: CN106749101, 2017, A. Location in patent: Paragraph 0037; 0038 [3] Bioorganic and Medicinal Chemistry Letters, 2011, vol. 21, # 8, p. 2394 - 2399 [4] Bioorganic and Medicinal Chemistry Letters, 2016, vol. 26, # 19, p. 4666 - 4670 [5] Pharmazie, 1980, vol. 35, # 2, p. 69 - 72 [6] Helvetica Chimica Acta, 1941, vol. 24, p. 209 E, 220 E [7] Journal of the American Chemical Society, 1945, vol. 67, p. 735,737 [8] Zhurnal Obshchei Khimii, 1953, vol. 23, p. 278,282;engl.Ausg.S.291,294 [9] Helvetica Chimica Acta, 1941, vol. 24, p. 209 E, 220 E [10] Journal of the American Chemical Society, 1945, vol. 67, p. 735,737 [11] Zhurnal Obshchei Khimii, 1953, vol. 23, p. 278,282;engl.Ausg.S.291,294 [12] Patent: WO2003/101931, 2003, A2. Location in patent: Page 20 [13] Patent: WO2006/44823, 2006, A2. Location in patent: Page/Page column 161 [14] Patent: WO2013/76590, 2013, A1. Location in patent: Page/Page column 40 [15] RSC Advances, 2015, vol. 5, # 125, p. 103172 - 103183 [16] Archiv der Pharmazie, 2018, vol. 351, # 8,
合成路线 2(2. 合成:1458-63-5)
产率:94.4%
合成条件:With sodium hydroxide; potassium carbonate In diethyl ether; water for 1 h;
实验步骤:将N-(3-氯丙基) - 哌啶盐酸盐(来自Aldrich Chemicals的纯度为97%)(100g)溶解在水(150mL)中,并向其中缓慢加入饱和碳酸钾水溶液(250mL)。 此外,加入ION氢氧化钠(25mL)和乙醚(250mL)并将混合物搅拌1小时。 分层; 将有机层用无水碳酸钾干燥,并在Biichi Labortechnik AGRotavapor上浓缩。 蒸发,得到标题化合物(77.2g,94.4%),将其不经纯化用于下一步反应
参考文献:
- [1] Patent: WO2008/42896, 2008, A2. Location in patent: Page/Page column 23 [2] Patent: US2013/303531, 2013, A1. Location in patent: Paragraph 0107; 0111; 0112 [3] Patent: WO2008/42896, 2008, A2. Location in patent: Page/Page column 23 [4] Patent: US2010/16282, 2010, A1. Location in patent: Page/Page column 24