6368-20-3 (R)-2-((叔丁氧羰基)氨基)-3-羟基丙酸

运输信息：常温运输。危险描述：非危险化学品，WGK Germany:3，海关编码:29241990，存储类别:13 - 不可燃性固体

Boc-D-丝氨酸是在有机合成中含有叔丁氧羰基保护的氨基不受亲电分子影响的D-丝氨酸，可用于合成乙酰氨基甲氧基丙酸酰胺（一种有效的抗惊厥药物），也用于化学合成。

化学合成; 医药

合成路线 1（1. 合成：6368-20-3）

产率：100% 合成条件：With sodium hydroxide In water at -5 - 35℃; for 20 h; 实验步骤：将氢氧化钠（8.4g，0.110mol）在室温（53ml）中溶于水中，冷却至5-10℃，并在≤10℃下加入D-丝氨酸（10.5g，0.100mol）和二碳酸二叔丁酯（26.2g，0.120mol），加热至30-35℃反应20小时，得到化合物I型水溶液（产率按100％计，HPLC纯度99.1％，手性纯度99.4percent）。式I化合物无需分离，反应溶液直接用于下一步合成。 参考文献：[1] Journal of the American Chemical Society, 1994, vol. 116, #18, p. 8402 - 8403 [2] Journal of the American Chemical Society, 2008, vol. 130, #7, p. 2351 - 2364 [3] Advanced Synthesis and Catalysis, 2016, vol. 358, #1, p. 34 - 40 [4] Patent: CN104030943, 2016, B. Location in patent: Paragraph 0095; 0096 [5] Beilstein Journal of Organic Chemistry, 2014, vol. 10, p. 1114 - 1120 [6] Medicinal Chemistry, 2014, vol. 10, #6, p. 609 - 618 [7] Chinese Chemical Letters, 2012, vol. 23, #6, p. 661 - 664 [8] Patent: US2014/323738, 2014, A1. Location in patent: Paragraph 0042 [9] Patent: CN106957239, 2017, A. Location in patent: Paragraph 0036-0039 [10] Patent: US2003/166616, 2003, A1 [11] Patent: EP1338592, 2003, A1 [12] Patent: US2011/34731, 2011, A1. Location in patent: Page/Page column 7 [13] European Journal of Medicinal Chemistry, 2018, vol. 143, p. 1489 - 1509 [14] Tetrahedron Letters, 1989, vol. 30, #50, p. 7021 - 7024 [15] Tetrahedron Letters, 1989, vol. 30, #23, p. 3027 - 3028 [16] Journal of Organic Chemistry, 1987, vol. 52, #12, p. 2361 - 2364 [17] Tetrahedron Letters, 1993, vol. 34, #42, p. 6705 - 6708 [18] Tetrahedron, 1995, vol. 51, #29, p. 8121 - 8134 [19] Tetrahedron Letters, 1995, vol. 36, #35, p. 6235 - 6238 [20] Tetrahedron Letters, 1996, vol. 37, #50, p. 8971 - 8974 [21] Synthesis, 1998, #12, p. 1707 - 1709 [22] Bioorganic and medicinal chemistry letters, 2003, vol. 13, #2, p. 237 - 240 [23] Organic Letters, 2003, vol. 5, #23, p. 4253 - 4256 [24] Journal of Organic Chemistry, 2005, vol. 70, #7, p. 2430 - 2438 [25] Journal of Organic Chemistry, 2009, vol. 74, #11, p. 4149 - 4157 [26] Patent: US2004/14816, 2004, A1. Location in patent: Page/Page column 11 [27] Tetrahedron, 2010, vol. 66, #29, p. 5384 - 5395 [28] Nature Chemistry, 2010, vol. 2, #4, p. 280 - 285 [29] Organic and Biomolecular Chemistry, 2011, vol. 9, #5, p. 1356 - 1365 [30] Patent: WO2011/95995, 2011, A1. Location in patent: Page/Page column 10-11 [31] Patent: WO2011/99033, 2011, A1. Location in patent: Page/Page column 42 [32] Patent: WO2012/1710, 2012, A1. Location in patent: Page/Page column 10-12; 18 [33] Patent: WO2012/46245, 2012, A1. Location in patent: Page/Page column 7 [34] ChemMedChem, 2012, vol. 7, #7, p. 1230 - 1236 [35] Patent: US2013/35508, 2013, A1. Location in patent: Paragraph 0031 [36] Patent: US2013/102811, 2013, A1. Location in patent: Paragraph 0041 [37] Patent: WO2014/155264, 2014, A1. Location in patent: Page/Page column 11-12 [38] ACS Medicinal Chemistry Letters, 2015, vol. 6, #5, p. 537 - 542 [39] Journal of Medicinal Chemistry, 2015, vol. 58, #10, p. 4204 - 4219 [40] Patent: WO2016/44770, 2016, A1. Location in patent: Page/Page column 732; 733 [41] Journal of Peptide Science, 2017, vol. 23, #3, p. 202 - 214 [42] Organic Syntheses, 1992, vol. 70, p. 18 - 18 [43] Patent: WO2018/60781, 2018, A1. Location in patent: Page/Page column 16-17 [44] Journal of Organic Chemistry, 2018, vol. 83, #13, p. 7085 - 7101

合成路线 2（2. 合成：6368-20-3）

产率：89% 合成条件：With triethylamine In water; acetone at 25℃; for 11 h; 实验步骤：通用方法：使L-苯丙氨酸（1.0g，6.05mmol）和碳酸钠（0.71g，6.70mmol）的水（10mL）溶液与2（1.89g，6.36mmol）的丙酮（10mL）溶液反应。通过TLC监测，将反应混合物在室温下搅拌直至反应完成。浓缩所得溶液，向残余物中加入水（10mL）和乙酸乙酯（10mL），用10％KHSO₄将pH调节至6.0并搅拌5分钟。除去有机层，用0％KHSO₄在0-5℃下将水层酸化至pH2.0，并用乙酸乙酯（2×10mL）萃取。将合并的有机层用5％NaHCO₃溶液，水，盐水洗涤，并经无水Na₂SO₄干燥。浓缩乙酸乙酯层，残余物用EtOAc/正己烷（2：8）混合物结晶，得到白色固体产物（1.53g，收率95％）。 参考文献：[1] Synthetic Communications, 2017, vol. 47, #22, p. 2127 - 2132

在碱性条件下以DL-丝氨酸和氯乙酰氯为原料反应，减压蒸干后用乙酸乙酯萃取，经活性炭处理、酰化酶I拆分后得D-丝氨酸。D-丝氨酸经二碳酸二叔丁酯的氨基保护，制备得到目标化合物Boc-D-丝氨酸。