144978-12-1 N-Boc-L-焦谷氨酸乙酯

运输信息：常温运输。危险描述：非危险化学品。

化学合成。

化学合成

路线1：

• 步骤: 向（S）-2-乙基5-氧代吡咯烷-1,2-二羧酸-1-叔丁酯和二叔丁基酯的溶液中，在0℃下加入碳酸氢盐的乙腈溶液，再加入4-（二甲基氨基）吡啶，室温搅拌过夜，真空浓缩后经快速色谱法纯化得到产物。
• 条件: With dmap In acetonitrile at 20℃;
• 收率: 100%
• 参考文献: [1] Patent: US2008/9497, 2008, A1. Location in patent: Page/Page column 70-71 [2] Patent: EP2272825, 2015, B1. Location in patent: Paragraph 0138; 0139 [3] Organic Preparations and Procedures International, 2001, vol. 33, # 4, p. 405 - 409 [4] Organic and Biomolecular Chemistry, 2006, vol. 4, # 21, p. 3894 - 3897 [5] Patent: US2011/34438, 2011, A1. Location in patent: Page/Page column 25-26 [6] Tetrahedron Letters, 1996, vol. 37, # 44, p. 7963 - 7966 [7] Chemical Communications, 2014, vol. 50, # 68, p. 9690 - 9692 [8] Patent: WO2017/189866, 2017, A1. Location in patent: Paragraph 0171 [9] Patent: EP2730572, 2014, A1. Location in patent: Paragraph 0450 [10] Patent: EP2730572, 2015, B1. Location in patent: Paragraph 0450 [11] Patent: EP2730572, 2015, B1. Location in patent: Paragraph 0448; 0450 [12] Tetrahedron, 2010, vol. 66, # 25, p. 4462 - 4468 [13] Bioorganic and Medicinal Chemistry, 2014, vol. 22, # 4, p. 1383 - 1393 [14] Bioorganic and Medicinal Chemistry Letters, 1998, vol. 8, # 22, p. 3193 - 3198 [15] Organic and Biomolecular Chemistry, 2011, vol. 9, # 20, p. 7042 - 7056 [16] Patent: WO2006/116157, 2006, A2. Location in patent: Page/Page column 114 [17] Tetrahedron Letters, 2003, vol. 44, # 15, p. 3203 - 3205 [18] Journal of Medicinal Chemistry, 2006, vol. 49, # 12, p. 3520 - 3535 [19] Organic and Biomolecular Chemistry, 2006, vol. 4, # 14, p. 2696 - 2709 [20] Patent: US2002/19411, 2002, A1 [21] Patent: WO2008/81399, 2008, A2. Location in patent: Page/Page column 84 [22] Bioorganic and Medicinal Chemistry Letters, 2008, vol. 18, # 15, p. 4360 - 4363 [23] Patent: EP3000893, 2016, A2. Location in patent: Paragraph 0041; 0111

路线2：

• 步骤: 向500ml四颈烧瓶中加入L-谷氨酸二乙酯盐酸盐、2-甲基四氢呋喃、碳酸钾和氯甲酸叔丁酯，在25-30℃反应5小时，75-80℃反应7小时，冷却后过滤，蒸馏回收溶剂，重结晶得到产物。
• 条件: With potassium carbonate In 2-methyltetrahydrofuran at 25 - 80℃; for 12 h;
• 收率: 89.3%
• 参考文献: [1] Patent: CN107602436, 2018, A. Location in patent: Paragraph 0060; 0061

路线3：

• 步骤: 向圆底烧瓶中加入L-焦谷氨酸和乙醇，冷却至0℃滴加亚硫酰氯，温热至室温搅拌16小时，减压浓缩后得到（S）-5-氧代吡咯烷-2-羧酸乙酯盐酸盐；向其中加入乙腈、DIPEA和DMAP，0℃滴加氯甲酸叔丁酯，温热至室温搅拌，减压浓缩后经洗涤、干燥、快速色谱纯化得到产物。
• 条件: With dmap; N-ethyl-N,N-diisopropylamine In acetonitrile at 0 - 20℃; for 54 h;
• 收率: 71%
• 参考文献: [1] Patent: US9458193, 2016, B1. Location in patent: Page/Page column 67