Boc-L-丝氨酸甲酯可作为有机合成中间体和医药中间体，主要用于实验室研发过程和化工生产过程中。制备：将3.1kgL-丝氨酸溶于30L甲醇之中，室温下加入氯化亚砜2.2L，加完后搅拌2h再升温回流8小时，将反应液浓缩旋干，将浓缩液溶于30L二氯甲烷，加入9.2L三乙胺和7.25kg二碳酸二叔丁酯，冰水冷却，控制温度不超过20℃，加毕，室温搅拌8h，将反应液用1N硫酸氢钠溶液、5％碳酸氢钠溶液、10％柠檬酸和饱和食盐水洗涤，有机相用无水硫酸钠干燥，减压去溶剂得化合物Ⅰ6.38kg，产率94％。
化学合成；生命科学；医药中间体
合成路线 1（1. 合成：2766-43-0）
- 步骤: 将粗制的（5）- 2-氨基-3-羟基丙酸甲酯盐酸盐（0.29mol）悬浮在DCM（200mL）中并向该混合物中加入三乙胺（79mL，0.57mol）和Boc 2 O（68g，0.31mol）。在0°C。移去冷却浴，将反应混合物在环境温度下搅拌过夜，然后用MTBE（300mL）稀释。过滤混合物，减压浓缩滤液。通过硅胶快速柱色谱法纯化残余物，得到（5）-2-（（叔丁氧基羰基）氨基）-3-羟基丙酸甲酯（60g，94％收率），为无色油状物。
- 条件: With triethylamine In dichloromethane at 0 - 20℃;
- 产率: 94%
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合成路线 2（2. 合成：2766-43-0）
- 步骤: 向在冰浴上冷却的4（1.26g，6.1mmol）和碳酸钾（0.91g，6.6mmol）在DMF（12mL）中的溶液中加入碘甲烷（0.80mL，12.8mmol）在DMF中的溶液（6mL））。在冰浴上搅拌30分钟后，将混合物在室温下搅拌4小时。滤出沉淀物，向滤液中加入水并用EtOAc萃取。将有机层用水和盐水洗涤，经MgSO 4干燥并蒸发。通过硅胶柱色谱法（己烷：EtOAc = 1：1）纯化获得的无色油状物，得到5，为无色油状物（1.24g，93％）。光谱数据5与文献相同，25，确认纯度通过1H NMR。
- 条件: With potassium carbonate In N,N-dimethyl-formamide at 20℃; for 4.50 h; Cooling with ice
- 产率: 93%
- 参考文献: [1] Organic Letters, 2003, vol. 5, #23, p. 4253 - 4256 [2] Arkivoc, 2016, vol. 2017, #2, p. 260 - 271 [3] Patent: EP2319850, 2011, A1. Location in patent: Page/Page column 8 [4] Tetrahedron Letters, 2003, vol. 44, #28, p. 5251 - 5253 [5] Journal of the American Chemical Society, 2006, vol. 128, #51, p. 16684 - 16691 [6] Bioorganic and Medicinal Chemistry Letters, 2009, vol. 19, #15, p. 4427 - 4431 [7] Organic and Biomolecular Chemistry, 2005, vol. 3, #13, p. 2476 - 2481 [8] Bioorganic and Medicinal Chemistry Letters, 1998, vol. 8, #2, p. 179 - 182 [9] European Journal of Organic Chemistry, 1998, #6, p. 945 - 959 [10] Tetrahedron Letters, 2001, vol. 42, #34, p. 5953 - 5954 [11] Tetrahedron Letters, 2007, vol. 48, #16, p. 2857 - 2859 [12] Chemistry - A European Journal, 2009, vol. 15, #17, p. 4428 - 4436 [13] Nature Chemistry, 2010, vol. 2, #4, p. 280 - 285 [14] Synthesis, 2010, #18, p. 3063 - 3066 [15] Medicinal Chemistry, 2014, vol. 10, #6, p. 609 - 618 [16] Patent: US2015/51183, 2015, A1. Location in patent: Paragraph 0460 [17] Organic Syntheses, 1992, vol. 70, p. 18 - 18 [18] Tetrahedron, 2018, vol. 74, #38, p. 5392 - 5398 [19] Journal of Organometallic Chemistry, 2018, vol. 876, p. 1 - 9
合成路线 3（3. 合成：2766-43-0）
- 步骤: 通用方法：将L-苯丙氨酸甲酯盐酸盐（5.0g，23.2mmol），三乙胺（2.47g，24.4mmol）和2（7.24g，24.4mmol）加入到二氯甲烷（50mL）中并在回流温度下搅拌（38 -40°C）5小时。反应完成后，过滤除去盐，滤液用5％KHSO 4（20mL），水（25mL），盐水（25mL）洗涤，并用硫酸钠干燥。减压蒸发溶剂，得到浅黄色油状物。通过柱色谱（硅胶，乙酸乙酯/己烷，8：2）纯化油状物，得到5.96g（92％）无色油状的（叔丁氧基羰基）-L-苯丙氨酸甲酯。
- 条件: With triethylamine In dichloromethane at 38 - 40℃;
- 产率: 81%
- 参考文献: [1] Synthetic Communications, 2017, vol. 47, #22, p. 2127 - 2132
