33233-67-9 4-[(叔丁氧羰基氨基)甲基]苯甲酸

危险性质：非危险化学品

作为医药中间体，用于药物合成（如专利WO2008/53131等文献中提及的药物研发）。

医药

合成路线 1（1. 合成：33233-67-9）

产率：97% 合成条件：Stage #1: With sodium hydrogencarbonate In tetrahydrofuran; water for 16 h; Stage #2: With hydrogenchloride; water In tetrahydrofuran 实验步骤：第1阶段 - Boc保护; 在室温下，将4-（氨基甲基）苯甲酸（10.00g，65.36mmol）与Boc 2 O（28.0g，130.72mmol）在H 2 O（100mL）和THF（100mL）中一起搅拌。 加入饱和NaHCO 3（水溶液）直至达到pH6并将反应搅拌16小时。 然后用1M HCl溶液将反应小心酸化至pH3，这导致固体沉淀出来。 将该EPO 60过滤并干燥，得到产物，为白色固体（16.1g，97％）。 m / z = 274 [M + Na] +。 参考文献：

• [1] Patent: WO2008/53131, 2008, A1. Location in patent: Page/Page column 58; 59-60 [2] Patent: WO2008/40934, 2008, A1. Location in patent: Page/Page column 57-58 [3] Patent: WO2010/20556, 2010, A1. Location in patent: Page/Page column 206 [4] Journal of Medicinal Chemistry, 2016, vol. 59, # 3, p. 965 - 984 [5] Journal of the Chemical Society - Perkin Transactions 1, 1999, # 4, p. 501 - 508 [6] Journal of Organic Chemistry, 1996, vol. 61, # 25, p. 8811 - 8818 [7] Patent: US2012/209005, 2012, A1. Location in patent: Page/Page column 35 [8] European Journal of Medicinal Chemistry, 2017, vol. 129, p. 124 - 134 [9] Journal of the American Chemical Society, 2017, vol. 139, # 50, p. 18365 - 18375 [10] Journal of Medicinal Chemistry, 2001, vol. 44, # 10, p. 1491 - 1508 [11] Patent: EP1080070, 2006, B1. Location in patent: Page/Page column 12 [12] Journal of the American Chemical Society, 2010, vol. 132, # 49, p. 17366 - 17369 [13] Journal of Medicinal Chemistry, 2012, vol. 55, # 7, p. 3331 - 3341 [14] Patent: WO2011/23986, 2011, A1. Location in patent: Page/Page column 29; 31 [15] Bioorganic Chemistry, 2002, vol. 30, # 4, p. 285 - 301 [16] Journal of Medicinal Chemistry, 1995, vol. 38, # 19, p. 3798 - 3805 [17] Tetrahedron Letters, 2008, vol. 49, # 42, p. 6033 - 6035 [18] Organic and Biomolecular Chemistry, 2008, vol. 6, # 23, p. 4356 - 4373 [19] Patent: US5166403, 1992, A [20] Chemistry - A European Journal, 2014, vol. 20, # 5, p. 1258 - 1262 [21] Patent: WO2011/154708, 2011, A1. Location in patent: Page/Page column 65-66 [22] Bioorganic and Medicinal Chemistry Letters, 2016, vol. 26, # 16, p. 4133 - 4139 [23] Chemical Communications, 2015, vol. 51, # 44, p. 9197 - 9200 [24] Patent: US6375926, 2002, B1 [25] Patent: US2012/295874, 2012, A1. Location in patent: Page/Page column 174 [26] Journal of Medicinal Chemistry, 1986, vol. 29, # 4, p. 448 - 453 [27] Journal of Medicinal Chemistry, 2008, vol. 51, # 8, p. 2447 - 2456 [28] Patent: WO2011/21209, 2011, A1. Location in patent: Page/Page column 49; 50 [29] Patent: US2012/101099, 2012, A1. Location in patent: Page/Page column 18; 19 [30] Patent: US2006/287522, 2006, A1. Location in patent: Page/Page column 50 [31] Patent: WO2009/47615, 2009, A2. Location in patent: Page/Page column 24 [32] Patent: US2010/222379, 2010, A1. Location in patent: Page/Page column 11 [33] Bioorganic and Medicinal Chemistry Letters, 2000, vol. 10, # 6, p. 553 - 557 [34] Bioorganic and Medicinal Chemistry Letters, 2001, vol. 11, # 11, p. 1359 - 1362 [35] Bioorganic and Medicinal Chemistry, 2003, vol. 11, # 6, p. 1021 - 1029 [36] Journal of Medicinal Chemistry, 2004, vol. 47, # 10, p. 2411 - 2413 [37] Journal of Medicinal Chemistry, 2005, vol. 48, # 17, p. 5530 - 5535 [38] Patent: US6521658, 2003, B1 [39] Patent: US5486525, 1996, A [40] Patent: US5656660, 1997, A [41] Patent: EP1273571, 2003, A1 [42] Patent: US7169759, 2007, B1. Location in patent: Page/Page column 11; 24-25 [43] Patent: US6680311, 2004, B1. Location in patent: Page/Page column 151 [44] Patent: EP1181269, 2004, B1. Location in patent: Page 21 [45] Patent: EP1389460, 2004, A1. Location in patent: Page/Page column 44 [46] Patent: WO2004/89925, 2004, A1. Location in patent: Page 72 [47] Patent: EP1550657, 2005, A1. Location in patent: Page/Page column 109 [48] Russian Journal of General Chemistry, 2010, vol. 80, # 12, p. 2572 - 2589 [49] Journal of the American Chemical Society, 2012, vol. 134, # 10, p. 4465 - 4468 [50] RSC Advances, 2014, vol. 4, # 76, p. 40444 - 40448 [51] Patent: WO2017/87695, 2017, A1. Location in patent: Paragraph 00103; 00104 [52] Patent: US5231102, 1993, A

合成路线 2（2. 合成：33233-67-9）

产率：97% 合成条件：With sodium hydrogencarbonate In tetrahydrofuran; water at 0℃; 实验步骤：将4-氨基甲基苄醇（1.0g，6.60mmol）在THF（10mL）和水（10mL）的混合物中浆化。 加入饱和碳酸氢钠溶液直至溶液的pH> 9。将混合物冷却至0℃并加入二碳酸二叔丁酯（2.89g，13.23mmol）。 将反应搅拌过夜，然后在真空下除去THF。 用EtOAc（20mL）萃取含水混合物，然后通过加入1N HCl酸化至pH 3。 将其用EtOAc（2×10mL）萃取，合并有机层，干燥（MgSO 4）并蒸发至干，得到所需产物（1.60g，97％）。 m / z 252 [M + + + H] + 参考文献：

• [1] Patent: WO2006/117549, 2006, A1. Location in patent: Page/Page column 147

合成路线 3（3. 合成：33233-67-9）

产率：52% 合成条件：Stage #1: With sodium hydroxide In ethanol at 10 - 15℃; Stage #2: at 15 - 20℃; Stage #3: With hydrogenchloride In water 实验步骤：将4-（氨基甲基）苯甲酸盐酸盐（8.0g，52mmol）溶解在EtOH（200mL）中并将溶液冷却至10-15℃并用10％w / v NaOH溶液碱化至pH8。 在15℃下滴加在EtOH（50mL）中的Boc 2 O（12.7g，58mmol），然后将反应在环境温度下搅拌H h。 真空除去溶剂，加入水（100mL）。 将水溶液用EtOAc（100mL）萃取，并将水层用5N HCl（aq）酸化至pH 1。 将水层用EtOAc（3×100mL）萃取，并将合并的有机萃取物用饱和盐水（100mL）洗涤。 真空除去溶剂，得到标题化合物，为白色固体。 无需进一步纯化。 产量：7.0克，52％。 参考文献：

• [1] Patent: WO2010/20556, 2010, A1. Location in patent: Page/Page column 68