89151-44-0 N-Boc-4-哌啶乙醇

危险性质：非危险化学品

化学合成。

化学合成

合成路线 1（1. 合成：89151-44-0）

产率：86% 合成条件：Stage #1: With palladium 10% on activated carbon; hydrogen In methanolInert atmosphere Stage #2: With diisobutylaluminium hydride In diethyl ether at -20℃; for 0.17 h; 实验步骤：将上述得到的产物（639mg，2.4mmol）溶解在6ml甲醇中，Underargon加入氩气，用氢气置换三次，并在氢化装置（4atm H2）中反应过夜。将反应溶液通过硅藻土过滤并用乙酸乙酯洗涤。浓缩滤液，通过柱色谱法分离，得到白色固体，722mg，收率100％。将上述产物（506mg，1.9mmol）溶于10ml乙醚中，将反应物冷却至-20℃，加入氢化二异丁基铝（1.0M，5mL，5mmol），反应10分钟直至原料消失。然后倒入饱和酒石酸钠钾溶液中，在室温下搅拌3小时以澄清反应混合物，水相用乙醚萃取三次，合并有机相，用饱和NaClsolution洗涤，用Na2SO4干燥，浓缩后，进行柱色谱分离，得到白色固体，368mg，收率86％。 参考文献：

• [1] Patent: CN102952072, 2016, B. Location in patent: Paragraph 0110-0111 [2] Bioorganic and Medicinal Chemistry Letters, 2003, vol. 13, # 13, p. 2167 - 2172 [3] Patent: US2012/71461, 2012, A1 [4] Patent: CN107793408, 2018, A [5] Patent: WO2018/68297, 2018, A1 [6] Patent: US6140333, 2000, A

合成路线 2（2. 合成：89151-44-0）

产率：91% 合成条件：With lithium triethylborohydride In tetrahydrofuran at -78 - 1℃; for 1 h; Inert atmosphere 实验步骤：在-78℃，在氮气氛下，向4-（2-乙氧基-2-氧代乙基）哌啶-1-羧酸叔丁酯（22g，81mmol）的无水THF（100mL）溶液中加入Super-H（200） mL，200mmol，1M在THF中）。 将所得混合物在室温下搅拌1小时，然后在0℃用MeOH（10mL）和饱和NH 4 Cl水溶液（100mL）处理。将混合物在室温下搅拌1小时，并用EtOAc（200mL×3）萃取。 减压浓缩有机层，通过硅胶色谱（硅胶：300-400目，PE / EtOAc 5/1至2/1）纯化残余物，得到4-（2-羟乙基）哌啶叔丁酯 -1-羧酸盐（17g，91）。 LRMS m / z（M-100）130.1发现，需要130.1。 参考文献：

• [1] European Journal of Organic Chemistry, 2014, vol. 2014, # 33, p. 7413 - 7425 [2] Patent: WO2018/68297, 2018, A1. Location in patent: Page/Page column 136 [3] Bioorganic and Medicinal Chemistry Letters, 2003, vol. 13, # 13, p. 2167 - 2172 [4] Patent: US2003/191316, 2003, A1. Location in patent: Page/Page column 32-33 [5] Patent: US2012/71461, 2012, A1. Location in patent: Page/Page column 124; 132 [6] European Journal of Medicinal Chemistry, 2016, vol. 123, p. 332 - 353 [7] Patent: CN107793408, 2018, A. Location in patent: Paragraph 0168; 0172

合成路线 3（3. 合成：89151-44-0）

产率：98% 合成条件：at 20℃; for 16 h; 实验步骤：在室温下向搅拌的2-哌啶-4-基乙醇（25.5g，197mmol）的四氢呋喃（250mL）溶液中加入二碳酸二叔丁酯（43.0g，197mmol）。 16小时后，将反应混合物减压浓缩，得到4-（2-羟乙基）哌啶-1-羧酸叔丁酯（44.3g，98％），为无色油状物。 1H NMR（300MHz，CDCl3）δ4.11-4.05（m，2H），3.72-3.66（m，2H），2.73-2.65（m，2H），1.74-1.59（m，4H），1.55-1.43（m ，2H），1.38（s，9H），1.19-1.09（m，2H）。 参考文献：

• [1] Tetrahedron Letters, 2006, vol. 47, # 15, p. 2515 - 2516 [2] Journal of Medicinal Chemistry, 1997, vol. 40, # 12, p. 1779 - 1788 [3] Journal of Medicinal Chemistry, 2005, vol. 48, # 6, p. 2100 - 2107 [4] Patent: EP2202223, 2010, A1. Location in patent: Page/Page column 52 [5] Journal of the American Chemical Society, 2016, vol. 138, # 16, p. 5433 - 5440 [6] Organic Letters, 2016, vol. 18, # 14, p. 3350 - 3353 [7] Patent: US2004/67931, 2004, A1. Location in patent: Page/Page column 15 [8] Patent: WO2014/187762, 2014, A1. Location in patent: Page/Page column 57 [9] Patent: US2015/353489, 2015, A1. Location in patent: Paragraph 0097; 0137; 0138 [10] Organic and Biomolecular Chemistry, 2014, vol. 12, # 5, p. 783 - 794 [11] Patent: US2018/148452, 2018, A1. Location in patent: Paragraph 0181-0182 [12] Patent: WO2006/105796, 2006, A1. Location in patent: Page/Page column 47 [13] Patent: WO2004/76450, 2004, A1. Location in patent: Page 52 [14] Patent: WO2017/195216, 2017, A1. Location in patent: Page/Page column 193-194 [15] Patent: WO2004/94412, 2004, A1. Location in patent: Page 23 [16] Patent: CN103755686, 2016, B. Location in patent: Paragraph 0101; 0102 [17] Bioorganic and Medicinal Chemistry, 1997, vol. 5, # 4, p. 693 - 705 [18] Journal of Labelled Compounds and Radiopharmaceuticals, 1999, vol. 42, # SUPPL. 1, p. S785-S786 [19] Bioorganic and Medicinal Chemistry Letters, 2003, vol. 13, # 1, p. 119 - 123 [20] Patent: US6664265, 2003, B2. Location in patent: Page column 33, 34 [21] Patent: WO2004/54973, 2004, A2. Location in patent: Page 28 [22] Patent: US6303609, 2001, B1 [23] Patent: US5594023, 1997, A [24] Patent: WO2006/46031, 2006, A1. Location in patent: Page/Page column 78 [25] Patent: US4489075, 1984, A [26] Patent: US6248755, 2001, B1 [27] Patent: WO2006/107771, 2006, A2. Location in patent: Page/Page column 55-56 [28] Patent: US2003/139441, 2003, A1 [29] Patent: US6677347, 2004, B2 [30] Patent: US2007/275906, 2007, A1. Location in patent: Page/Page column 24-25 [31] Patent: US2008/176901, 2008, A1. Location in patent: Page/Page column 8 [32] Patent: US6660735, 2003, B2. Location in patent: Page column 39, 40 [33] Bioorganic and Medicinal Chemistry Letters, 2008, vol. 18, # 16, p. 4670 - 4674 [34] Patent: WO2008/97673, 2008, A1. Location in patent: Page/Page column 24 [35] Patent: WO2008/97676, 2008, A1. Location in patent: Page/Page column 26 [36] Patent: US2005/107434, 2005, A1. Location in patent: Page/Page column 13 [37] Patent: EP1602645, 2005, A1. Location in patent: Page/Page column 15-16 [38] Patent: EP1386920, 2004, A1. Location in patent: Page 44-45 [39] Patent: WO2004/20435, 2004, A1. Location in patent: Page 112 [40] Patent: US2011/294754, 2011, A1. Location in patent: Page/Page column 5 [41] Journal of Medicinal Chemistry, 2012, vol. 55, # 17, p. 7480 - 7501 [42] Patent: WO2013/158644, 2013, A2. Location in patent: Paragraph 00479; 00481; 00482 [43] Patent: US2015/31674, 2015, A1. Location in patent: Paragraph 0277 [44] Patent: WO2015/38649, 2015, A1. Location in patent: Paragraph 00532 [45] Patent: US2015/232444, 2015, A1. Location in patent: Paragraph 0420; 0421 [46] Patent: WO2015/134464, 2015, A2. Location in patent: Paragraph 00488; 00490 [47] Patent: WO2015/188085, 2015, A1. Location in patent: Paragraph 0372 [48] Patent: WO2007/122410, 2007, A1. Location in patent: Page/Page column 80-81