64318-28-1 4-羟基苯乙基氨基甲酸叔丁酯

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：64318-28-1）

产率：73% 合成条件：Stage #1: With sodium hydroxide In 1,4-dioxane; Al 2 O 3 ; water for 0.17 h; Stage #2: at 20℃; Inert atmosphere Stage #3: With hydrogenchloride In water; ethyl acetate 实验步骤：a）N-（叔丁氧基羰基）-2-（4-羟基苯基） - 乙胺的合成将盐酸盐酸盐（1.0g; 5.76mmol; 1eq。）溶于二恶烷和蒸馏水（25 / 12mL）的混合物中，然后加入NaOH（0.46g; 11.5mmol）在10mL蒸馏水中的溶液。将全部搅拌10分钟，然后加入二叔丁基碳酸氢盐（Boc 2 O）（1.26g; 5.76mmol; 2当量。在氩气和环境温度下将反应物搅拌过夜。蒸发二恶烷后，向残留的水相中加入40mL EtOAc，用1M的1M水溶液将混合物的pH降至7-8。然后分离各相，水相用EtOAc（2×15mL）洗涤。然后将合并的有机相用Na 2 SO 4干燥，过滤并蒸发。然后在色谱柱（Al 2 O 3，CH 2 Cl 2）中纯化粗产物。 / Hex，85：15）得到N-（叔丁氧基羰基）-2-（4-羟基苯基） - 乙胺（0.98g; 73％）.Mp：61-62℃.IR（KBr）：3378.9（-OH） ; -CONH-）1686.6（CO ）。UV-Vis（CH 2 Cl 2）：277（1803）.1 H-NMR（400MHz，CDCl 3）：1.441（s，9H，10）; 2.703（t，J = 7.9Hz; 2H，CH2CH2N）; 3.329（m，2H，CH2CH2N）; 4.602（宽s，1H，NH或OH）; 6.023（宽s，1H，NH或OH）; 6.774（d，J = 8.3Hz; 2H; ArH）; 7.013（d，J = 8.3Hz; 2H; ArH）.13C-NMR（100MHz，CDCl3）：28.84（CMe3）; 35.64（CH2CH2N）; 42.49（CH2CH2N）; 80.15（CMe3）; 115.97（Cm）; 130.18（公司）; 130.50（Cp）; 155.38（Cipso）; 156.84（CO）.C13H19O3N的计算的初步分析（237.29）：C，65.80％; H，8.07％; N，5.90％;发现：C，65.77％; H，8.09％; N，5.90％.IE MS：181 [M-（Me）3CO-H + Na] +; 107 [M-（Me）3COC（O）NHCH2] 参考文献：

• [1] Synthesis, 2009, # 22, p. 3838 - 3842 [2] Angewandte Chemie - International Edition, 2014, vol. 53, # 23, p. 5877 - 5881 [3] Angew. Chem., 2014, vol. 126, # 23, p. 5987 - 5991,5 [4] Journal of Heterocyclic Chemistry, 2001, vol. 38, # 3, p. 633 - 639 [5] Bioorganic and Medicinal Chemistry, 2009, vol. 17, # 15, p. 5496 - 5509 [6] Patent: US2011/184070, 2011, A1. Location in patent: Page/Page column 17 [7] Journal of Pharmacology and Experimental Therapeutics, 2000, vol. 292, # 3, p. 1135 - 1145 [8] Journal of Organic Chemistry, 2005, vol. 70, # 16, p. 6303 - 6312 [9] Patent: US5840726, 1998, A

合成路线 2（2. 合成：64318-28-1）

产率：91% 合成条件：With triethylamine In tetrahydrofuran; methanol at 0 - 20℃; 实验步骤：将酪胺（10g，72.90mmol）缓慢溶解在THF（即四氢呋喃，140ml）中。将三乙胺（7.36g，72.90mmol）加入到甲醇（20ml）中。 用冰盐浴将溶液冷却至0°，分批加入碳酸二叔丁酯（8.20g，87.48mmol）。 添加完成后，将其在0℃下搅拌1小时，然后在室温下搅拌过夜。 旋转干燥溶剂产品18.0g（91％）• 参考文献：

• [1] Patent: CN104341347, 2018, B. Location in patent: Paragraph 0097; 0098

合成路线 3（3. 合成：64318-28-1）

产率：100% 合成条件：With triethylamine In tetrahydrofuran; methanol at 0 - 20℃; 实验步骤：叔丁基[2-（4-羟基苯基）乙基]氨基甲酸酯; 将4-（2-氨基乙基）苯酚（2.00g，14.58mmol）溶于THF（70mL）和MeOH（10mL）中，并加入TEA（1.47g，14.58mmol）。 将混合物在冰浴中冷却。 加入二碳酸二叔丁酯（3.18g，14.58mmol）。 将混合物在0℃下搅拌1小时并在室温下放置过夜。 蒸发溶剂并对粗产物（ISOLUTE SI，（20g）进行柱色谱，用庚烷/ EtOAc（90:10），庚烷/ EtOAc（70:30）洗脱），得到标题化合物（3.47g，100％）。。 1H NMR（500MHz，CD3OD）：δ1.43（s，9H），2.66（t，2H），3.20（t，2H），6.72（d，2H），7.02（d，2H）; 质谱：M-H + 236。 参考文献：

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