74844-91-0 N-Boc-反式-4-羟基-L-脯氨酸甲酯

合成路线 2（2. 合成：74844-91-0）

• 步骤：由反式-4-羟基-L-脯氨酸合成化合物（2S，4R）-4-（叔丁基二甲基甲硅烷基氧基）-2-（羟甲基）-吡咯烷-1-羧酸叔丁酯（8），具体程序参考Rosen等，J.Med.Chem.1988,31,1598。
• 条件：With sodium carbonate In 1,4-dioxane; water
• 收率：100%
• 产物：1H NMR (400MHz, CDCl3) δ 0.08 (s, 6H), 0.87 (s, 9H), 1.47 (s, 9H), 1.96 (m, 1H), 1.98 (s, 1H), 3.34 (dd, J=4.0,14.6 Hz, 1H), 3.42 (d, J=12.0 Hz, 1H), 3.55 (m, 1H), 3.71 (m, 1H), 4.11 (m, 1H), 4.27 (m, 1H), 4.91 (dd, J=0.8Hz,12.0Hz,1H)
• 参考文献：[1] Tetrahedron Letters, 2001, vol.42, #32, p.5335-5338；[2] Bioorganic and Medicinal Chemistry, 2009, vol.17, #4, p.1557-1572；[3] Patent: US2007/117986, 2007, A1. Location in patent: Page/Page column 21; 22；[4] Journal of Organic Chemistry, 2005, vol.70, #2, p.499-504；[5] Tetrahedron Asymmetry, 2010, vol.21, #2, p.222-225；[6] Bioorganic and Medicinal Chemistry Letters, 2011, vol.21, #12, p.3771-3773；[7] Bioorganic and Medicinal Chemistry Letters, 2009, vol.19, #15, p.4130-4133；[8] Patent: WO2013/149121, 2013, A1. Location in patent: Page/Page column 132; 133；[9] Angewandte Chemie - International Edition, 2002, vol.41, #9, p.1600-1602；[10] Patent: WO2018/26792, 2018, A1. Location in patent: Page/Page column 63-64；[11] Patent: WO2018/152134, 2018, A1. Location in patent: Paragraph 000213；[12] ACS Medicinal Chemistry Letters, 2014, vol.5, #1, p.56-60；[13] Patent: WO2018/86139, 2018, A1. Location in patent: Page/Page column 181；[14] Journal of Organic Chemistry, 2006, vol.71, #14, p.5186-5190；[15] Patent: WO2017/177326, 2017, A1. Location in patent: Page/Page column 96; 97；[16] Patent: WO2018/191278, 2018, A2. Location in patent: Page/Page column 123；[17] ChemMedChem, 2018, vol.13, #3, p.220-226；[18] European Journal of Medicinal Chemistry, 2018, vol.152, p.358-369；[19] Journal of Antibiotics, 1996, vol.49, #5, p.478-484；[20] Tetrahedron Letters, 2005, vol.46, #45, p.7813-7816；[21] Patent: WO2016/73623, 2016, A2. Location in patent: Paragraph 0126；[22] Patent: WO2013/102242, 2013, A1. Location in patent: Page/Page column 71；[23] Tetrahedron Letters, 1992, vol.33, #52, p.8103-8104；[24] Bioorganic and Medicinal Chemistry Letters, 2001, vol.11, #4, p.587-590；[25] Synlett, 2001, #10, p.1575-1577；[26] Bioorganic and Medicinal Chemistry Letters, 2003, vol.13, #3, p.489-493；[27] Synthesis, 2004, #3, p.334-340；[28] Journal of Organic Chemistry, 2005, vol.70, #10, p.3826-3837；[29] Tetrahedron Letters, 2006, vol.47, #37, p.6553-6556；[30] Tetrahedron Letters, 2006, vol.47, #50, p.8929-8932；[31] Patent: US5756528, 1998, A；[32] Patent: EP1813614, 2007, A1. Location in patent: Page/Page column 41；[33] Tetrahedron Letters, 2009, vol.50, #20, p.2363-2366；[34] Patent: WO2010/62821, 2010, A1. Location in patent: Page/Page column 57；[35] Advanced Synthesis and Catalysis, 2012, vol.354, #6, p.1035-1042；[36] Journal of the Chinese Chemical Society, 2012, vol.59, #3, p.436-442；[37] Journal of Organic Chemistry, 2012, vol.77, #12, p.5286-5296；[38] European Journal of Organic Chemistry, 2012, #31, p.6280-6284,5；[39] European Journal of Organic Chemistry, 2012, #31, p.6280-6284；[40] Chemical Communications, 2013, vol.49, #40, p.4561-4563；[41] Bioorganic and Medicinal Chemistry, 2013, vol.21, #14, p.4092-4101；[42] Patent: US2013/287731, 2013, A1. Location in patent: Paragraph 0240；[43] RSC Advances, 2013, vol.3, #42, p.19533-19544；[44] Organic Process Research and Development, 2008, vol.12, #4, p.626-631；[45] Tetrahedron Asymmetry, 2014, vol.25, #3, p.212-218；[46] Patent: US2014/179680, 2014, A1. Location in patent: Paragraph 0766；[47] Organic and Biomolecular Chemistry, 2015, vol.13, #11, p.3171-3181；[48] Bioorganic and Medicinal Chemistry, 2017, vol.25, #1, p.138-152；[49] Patent: US9994614, 2018, B2. Location in patent: Page/Page column 60; 62

合成路线 3（3. 合成：74844-91-0）

• 步骤：向（4R）-1-Boc-4-羟基-L-脯氨酸（8g，34.63mmol）在DMF中的溶液中加入K₂CO₃（14g，101mmol）和碘甲烷（2.6ml，20.6mmol），反应混合物在室温下搅拌5小时。
• 条件：With potassium carbonate In N,N-dimethyl-formamide at 20℃; for 5 h
• 收率：95%
• 产物：甲基（2S，4R）-1-Boc-4-羟基吡咯烷-2-羧酸甲酯（8.0g，95%），MS [M+H]=246（M+1）
• 参考文献：[1] Patent: WO2008/7930, 2008, A1. Location in patent: Page/Page column 25；[2] Patent: US2010/120783, 2010, A1. Location in patent: Page/Page column 10；[3] Organic Letters, 2015, vol.17, #18, p.4620-4623；[4] Patent: WO2018/160889, 2018, A1. Location in patent: Page/Page column 645; 646；[5] Chemistry - A European Journal, 2006, vol.12, #15, p.4121-4143；[6] Organic Letters, 2016, vol.18, #24, p.6292-6295；[7] Tetrahedron Letters, 2011, vol.52, #52, p.7049-7053；[8] ACS Combinatorial Science, 2011, vol.13, #6, p.667-675；[9] Patent: WO2005/87760, 2005, A1. Location in patent: Page/Page column 19-20；[10] Patent: US5102877, 1992, A；[11] Advanced Synthesis and Catalysis, 2011, vol.353, #1, p.113-124；[12] Chimia, 2011, vol.65, #4, p.264-267；[13] Bioorganic and Medicinal Chemistry, 2011, vol.19, #24, p.7664-7678；[14] Patent: WO2017/189866, 2017, A1. Location in patent: Paragraph 0184