生命科学；化学合成，医药阿扎那韦中间体。N-甲氧羰基-L-叔亮氨酸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和化工生产过程中。制备：在L-丙氨酸(8 g, 168 mmol)的1N NaOH (168 mL)溶液中加入Na₂CO₃ (8.9 g, 84 mmol)。将溶液冷却至0°C，逐滴加入氯甲酸甲酯(20.5 mL, 172 mmol)。反应混合物在室温下搅拌3.5小时。溶液用Et₂O洗涤，用1N HCl酸化至pH约为1。水层用DCM提取，有机层用盐水洗涤，用Na₂SO₄干燥，浓缩得到目标中间体N-甲氧羰基-L-叔亮氨酸。
医药中间体；有机合成中间体
路线1：
- 步骤：(S)-2-氨基-3,3-二甲基丁酸的搅拌溶液（约5.0g，38.6mmol）在约0℃下，在二恶烷（约20ml）和氢氧化钠（2N，62ml，PH=8-9）中，逐滴加入甲基氯代甲酸酯（约5.88ml，76.33mmol）并在约60℃下搅拌。大约18个小时。将反应混合物冷却至室温，用DCM萃取，分离水层并用1N HCl酸化。将所得溶液用EtOAc萃取，经Na₂SO₄干燥，并在减压下蒸发溶剂。将所得粗产物在己烷中搅拌并蒸馏，得到标题化合物，为固体。
- 条件：With sodium hydroxide In 1,4-dioxane; water at 60℃; for 18 h;
- 产率：100%
- 参考文献：[1] Patent: WO2011/80562, 2011, A1. Location in patent: Page/Page column 34 [2] Patent: WO2005/61487, 2005, A1. Location in patent: Page/Page column 109 [3] Patent: US2005/159469, 2005, A1. Location in patent: Page/Page column 56 [4] Patent: EP2423187, 2012, A1. Location in patent: Page/Page column 11 [5] Patent: US2005/131017, 2005, A1. Location in patent: Page/Page column 95 [6] Patent: US2005/148623, 2005, A1. Location in patent: Page/Page column 126 [7] Organic Process Research and Development, 2004, vol. 8, # 3, p. 455 - 460 [8] Journal of Medicinal Chemistry, 1998, vol. 41, # 18, p. 3387 - 3401 [9] Organic Process Research and Development, 2008, vol. 12, # 1, p. 69 - 75 [10] Patent: US2017/28077, 2017, A1. Location in patent: Paragraph 0136 [11] Journal of Medicinal Chemistry, 2018, vol. 61, # 9, p. 4176 - 4188 [12] Organic Process Research and Development, 2002, vol. 6, # 3, p. 323 - 328 [13] Patent: WO2008/11117, 2008, A2. Location in patent: Page/Page column 452-453 [14] ACS Medicinal Chemistry Letters, 2014, vol. 5, # 3, p. 255 - 258 [15] European Journal of Medicinal Chemistry, 2017, vol. 125, p. 87 - 100 [16] Patent: WO2009/136365, 2009, A1. Location in patent: Page/Page column 16-17 [17] Patent: US2011/178305, 2011, A1. Location in patent: Page/Page column 6-7 [18] Patent: WO2011/107843, 2011, A2. Location in patent: Page/Page column 15; 16 [19] Patent: US2016/297804, 2016, A1. Location in patent: Paragraph 0154-0156
路线2：
- 步骤：将L-苏氨酸（0.50g，4.2mmol）和碳酸氢钠（1.13g，13.4mmol）溶解于水（20mL）中，然后在冰浴中冷却。将氯甲酸甲酯（0.36mL，4.62mmol）溶解在乙醚（2mL）中并在剧烈搅拌下滴加。将溶液在环境温度下搅拌5小时，然后用浓盐酸调节至pH 3并萃取到乙酸乙酯中。将有机溶液用硫酸钠干燥，过滤并浓缩，得到0.12g标题化合物，为蜡状固体。
- 条件：With sodium hydrogencarbonate In diethyl ether; water at 20℃; for 5 h; Cooling with ice
- 产率：74%
