106391-86-0 BOC-D-丙氨醇

运输信息：常温运输。危险描述：非危险化学品（但GHS分类显示具有皮肤刺激（2级）、严重眼刺激（2级）和呼吸道刺激（单次暴露）的危害；WGK Germany:3，F:10，海关编码29051990，存储类别为不可燃性固体13类。防护措施：需遵循P261、P264等多项预防声明。

N-Boc-D-丙氨醇属于手性氨基醇类，广泛用于医药、精细化工、材料和不对称催化的有机合成中，在医药领域主要应用于多肽类药物和喹诺酮类手性药物，在不对称催化领域用作金属手性配体和手性助剂的手性源。

多肽合成；氨基酸保护单体

合成路线 1（1. 合成：106391-86-0）

• 步骤: 将10克（133毫摩尔）（R）-2-氨基-1-丙醇和14.8克（146.5毫摩尔）三乙胺在500毫升四氢呋喃中的溶液冷却至0℃，一次性加入30克（133毫摩尔）二碳酸二叔丁酯，室温搅拌约18小时，减压浓缩后用乙酸乙酯溶解，依次用水、饱和氯化钠水溶液洗涤，硫酸镁干燥后减压浓缩得22g（94%）目标化合物。
• 条件: With triethylamine In tetrahydrofuran at 0 - 20℃; for 18 h
• 收率: 94%
• 参考文献: [1] Tetrahedron Letters, 2006, vol. 47, # 43, p. 7551 - 7556 [2] Patent: US7045545, 2006, B1. Location in patent: Page/Page column 26 [3] Letters in Organic Chemistry, 2010, vol. 7, # 5, p. 353 - 359 [4] Journal of Medicinal Chemistry, 2008, vol. 51, # 15, p. 4601 - 4608 [5] Patent: WO2014/159224, 2014, A1. Location in patent: Paragraph 00280 [6] Patent: WO2016/123707, 2016, A1. Location in patent: Paragraph 00176 [7] ACS Combinatorial Science, 2016, vol. 18, # 9, p. 569 - 574 [8] Journal of Medicinal Chemistry, 1999, vol. 42, # 23, p. 4749 - 4763 [9] Patent: WO2010/114179, 2010, A1. Location in patent: Page/Page column 65-66 [10] Journal of Medicinal Chemistry, 1999, vol. 42, # 18, p. 3463 - 3477 [11] Patent: US2009/170874, 2009, A1. Location in patent: Page/Page column 58 [12] Patent: US5672588, 1997, A [13] Tetrahedron Letters, 1990, vol. 31, # 19, p. 2661 - 2664 [14] Tetrahedron Asymmetry, 2002, vol. 13, # 11, p. 1129 - 1134 [15] Patent: US6391901, 2002, B1 [16] Patent: US2007/54915, 2007, A1. Location in patent: Page/Page column 49-50 [17] Journal of the American Chemical Society, 2010, vol. 132, # 3, p. 1151 - 1158 [18] Journal of Organic Chemistry, 2010, vol. 75, # 8, p. 2718 - 2721 [19] Bioorganic and Medicinal Chemistry Letters, 2012, vol. 22, # 8, p. 2877 - 2879 [20] Organic Process Research and Development, 2012, vol. 16, # 1, p. 109 - 116 [21] Patent: US6025382, 2000, A [22] Bioorganic and Medicinal Chemistry, 2012, vol. 20, # 21, p. 6305 - 6312,8 [23] Patent: WO2013/59163, 2013, A1. Location in patent: Page/Page column 35 [24] Patent: WO2014/13309, 2014, A1. Location in patent: Page/Page column 50 [25] Patent: WO2014/114249, 2014, A1. Location in patent: Page/Page column 19 [26] Patent: WO2015/110958, 2015, A1. Location in patent: Page/Page column 27-28 [27] Patent: US2016/75720, 2016, A1. Location in patent: Paragraph 0248 [28] Patent: US2016/332967, 2016, A1. Location in patent: Paragraph 0122 [29] Patent: WO2018/73602, 2018, A1. Location in patent: Page/Page column 104 [30] Patent: US2008/146565, 2008, A1. Location in patent: Page/Page column 97

合成路线 2（2. 合成：106391-86-0）

• 步骤: 将D-丙氨酸（3.5g，39.3mmol）分小份加入到LiAlH₄（2.89g，76.26mmol）在回流THF中的悬浮液中，继续回流12小时；冷却至0℃，小心加入15%NaOH水溶液（3ml）和水（9ml）淬灭过量试剂，室温搅拌10分钟后，加入（Boc）₂O（8.31g，38.13mmol）的CH₂Cl₂（40ml）溶液，60℃搅拌6小时，冷却至室温，通过无水Na₂SO₄垫过滤，滤液真空浓缩，硅胶柱色谱纯化得（S）-Boc-2-氨基-丙醇。
• 条件: Stage #1: With lithium aluminium tetrahydride In tetrahydrofuran for 12 h; Heating / reflux；Stage #2: With sodium hydroxide; water In tetrahydrofuran at 0 - 20℃; for 0.17 h；Stage #3: at 60℃; for 6 h
• 收率: 63%
• 参考文献: [1] Patent: WO2008/55840, 2008, A1. Location in patent: Page/Page column 58 [2] Patent: US2009/163502, 2009, A1. Location in patent: Page/Page column 40 [3] Patent: US2009/163499, 2009, A1. Location in patent: Page/Page column 28 [4] Patent: US2009/170873, 2009, A1. Location in patent: Page/Page column 42 [5] Patent: US2010/324069, 2010, A1. Location in patent: Page/Page column 24 [6] Patent: US2010/324070, 2010, A1. Location in patent: Page/Page column 19-20 [7] Patent: US2010/324056, 2010, A1. Location in patent: Page/Page column 30 [8] Patent: US2012/22067, 2012, A1. Location in patent: Page/Page column 36

合成路线 3（3. 合成：106391-86-0）

• 步骤: 将D-丙氨酸（3.5g，39.3mmol）分小份加入到LiAlH₄（2.89g，76.26mmol）在回流THF中的悬浮液中，继续回流12小时；冷却至0℃，小心加入15%NaOH水溶液（3ml）和水（9ml）淬灭过量试剂，室温搅拌10分钟后，加入（Boc）₂O（8.31g，38.13mmol）的CH₂Cl₂（40ml）溶液，60℃搅拌6小时，冷却至室温，通过无水Na₂SO₄垫过滤，滤液真空浓缩，硅胶柱色谱纯化得（S）-Boc-2-氨基-丙醇。
• 条件: Stage #1: With lithium aluminium tetrahydride In tetrahydrofuran for 12 h; Heating / reflux；Stage #2: at 60℃; for 6 h
• 收率: 63%
• 参考文献: [1] Patent: US2008/4442, 2008, A1. Location in patent: Page/Page column 196 [2] Tetrahedron Letters, 2002, vol. 43, # 52, p. 9691 - 9693 [3] Synlett, 2002, # 10, p. 1730 - 1732