40216-83-9 反式-4-羟基-L-脯氨酸甲酯盐酸盐

运输方式：冰袋运输。危险描述：非危险化学品，WGK Germany:3，海关编码29339900，存储类别11 - 可燃固体。

化学合成；作为L-脯氨酸衍生物，盐酸盐态增加溶解性和稳定性，用于药物制备和储存过程中维持性质和活性。

医药

路线1：

• 步骤：将（2S，4R）-4-羟基-2-吡咯烷羧酸盐酸盐的甲醇溶液在0℃加入亚硫酰氯，温热至室温后加热回流过夜，浓缩至干得产物。
• 条件：0-20℃；Reflux
• 产率：92%
• 参考文献：[1] Organic Letters, 2018, vol.20, #1, p.162-165；[2] Patent: WO2013/174937, 2013, A1；[3] Patent: US2015/152048, 2015, A1

路线2：

• 步骤：向（2S，4R）-4-羟基吡咯烷-2-甲酸的甲醇溶液中加入乙酰氯，0-20℃搅拌30分钟后，温热至室温搅拌2小时，减压除挥发物，乙醚研磨得产物。
• 条件：0-20℃；2.5小时；乙酰氯
• 产率：100%
• 参考文献：[1] Tetrahedron, 1995, vol.51, #9, p.2719-2728；[2] Journal of Organic Chemistry, 1996, vol.61, #14, p.4748-4755；[3] Tetrahedron, 1998, vol.54, #44, p.13391-13404；[4] Heterocycles, 2005, vol.65, #7, p.1705-1711；[5] Journal of the American Chemical Society, 2001, vol.123, #42, p.10245-10254；[6] Organic Letters, 2001, vol.3, #8, p.1241-1244；[7] Journal of Organic Chemistry, 2001, vol.66, #10, p.3593-3596；[8] Tetrahedron, 2007, vol.63, #30, p.7112-7119；[9] Heterocycles, 2003, vol.60, #5, p.1203-1209；[10] Journal of the Chinese Chemical Society, 2007, vol.54, #3, p.803-806；[11] Patent: WO2007/113634, 2007, A1；[12] Tetrahedron Asymmetry, 2009, vol.20, #12, p.1433-1436；[13] Journal of Organic Chemistry, 2012, vol.77, #11, p.4917-4923；[14] Tetrahedron Letters, 2012, vol.53, #30, p.3847-3849；[15] Tetrahedron Letters, 2013, vol.54, #39, p.5345-5347；[16] Patent: TW2017/8221, 2017, A；[17] Synlett, 2004, #6, p.1003-1006；[18] European Journal of Medicinal Chemistry, 2006, vol.41, #11, p.1347-1351；[19] Patent: WO2007/65883, 2007, A1；[20] Journal of the Chemical Society - Perkin Transactions 1, 1998, #22, p.3777-3793；[21] Bioorganic and Medicinal Chemistry, 2016, vol.24, #18, p.4016-4022；[22] Bioorganic and Medicinal Chemistry Letters, 2017, vol.27, #24, p.5424-5428；[23] Bioorganic and Medicinal Chemistry Letters, 2000, vol.10, #13, p.1421-1425；[24] European Journal of Medicinal Chemistry, 1996, vol.31, #9, p.717-723；[25] Heterocycles, 1998, vol.48, #11, p.2365-2378；[26] Patent: WO2018/26792, 2018, A1；[27] Journal of Heterocyclic Chemistry, 1990, vol.27, #7, p.2181-2187；[28] Bioorganic and Medicinal Chemistry Letters, 2011, vol.21, #12, p.3767-3770；[29] Journal of Organic Chemistry, 2018, vol.83, #11, p.6162-6170；[30] Patent: WO2008/147800, 2008, A1；[31] Chemical communications (Cambridge, England), 2003, #20, p.2606-2607；[32] Tetrahedron Letters, 2015, vol.56, #26, p.4036-4038；[33] Journal of Organic Chemistry, 1991, vol.56, #23, p.6672-6682；[34] Helvetica Chimica Acta, 1996, vol.79, #7, p.1825-1842；[35] Journal of the American Chemical Society, 1998, vol.120, #30, p.7439-7449；[36] Patent: WO2006/27694, 2006, A1；[37] Bioorganic and Medicinal Chemistry, 2014, vol.22, #11, p.3055-3064；[38] Organic and Biomolecular Chemistry, 2014, vol.12, #47, p.9638-9643；[39] Bioorganic and Medicinal Chemistry, 2015, vol.23, #24, p.7685-7693；[40] Synthesis, 1990, vol.1, #10, p.925-930；[41] Indian Journal of Chemistry, Section B: Organic Chemistry Including Medicinal Chemistry, 1989, vol.28, #1-11, p.294-296；[42] Bioorganic and Medicinal Chemistry, 2008, vol.16, #10, p.5398-5404；[43] European Journal of Medicinal Chemistry, 2008, vol.43, #10, p.2130-2139；[44] Bioorganic and Medicinal Chemistry, 2008, vol.16, #17, p.7932-7938；[45] Patent: WO2015/28850, 2015, A1；[46] Patent: WO2016/59622, 2016, A2；[47] Journal of Chemical Research, 2009, #11, p.668-670；[48] Journal of Organic Chemistry, 1981, vol.46, #21, p.4182-4187；[49] Tetrahedron Asymmetry, 1998, vol.9, #1, p.47-53；[50] Bioorganic and Medicinal Chemistry, 2002, vol.10, #5, p.1399-1415；[51] Tetrahedron, 2003, vol.59, #18, p.3307-3314；[52] Bioorganic and Medicinal Chemistry Letters, 2004, vol.14, #22, p.5699-5702；[53] Journal of Organic Chemistry, 2007, vol.72, #5, p.1830-1833；[54] Tetrahedron Letters, 2005, vol.46, #45, p.7705-7709；[55] Tetrahedron Letters, 2005, vol.46, #30, p.4985-4987；[56] Bioorganic and Medicinal Chemistry, 2004, vol.12, #19, p.5171-5180；[57] Bioorganic and Medicinal Chemistry, 2006, vol.14, #7, p.2253-2265；[58] Journal of Organic Chemistry, 2000, vol.65, #5, p.1590-1596；[59] Organic Letters, 2007, vol.9, #15, p.2939-2941；[60] Organic letters, 1999, vol.1, #10, p.1513-1516；[61] Bioorganic and Medicinal Chemistry, 2008, vol.16, #1, p.578-585；[62] Patent: WO2005/42533, 2005, A2；[63] Patent: EP1852436, 2007, A1；[64] Angewandte Chemie - International Edition, 2007, vol.46, #44, p.8431-8435；[65] Chemical Communications, 2009, #4, p.463-465；[66] Patent: US2009/163472, 2009, A1；[67] Patent: WO2004/99185, 2004, A1；[68] Chemistry - A European Journal, 2010, vol.16, #18, p.5333-5342；[69] Chemistry - A European Journal, 2010, vol.16, #35, p.10691-10706；[70] Organic Letters, 2010, vol.12, #24, p.5708-5711；[71] Patent: WO2011/50146, 2011, A1；[72] Patent: WO2013/49164, 2013, A1；[73] Patent: WO2013/49174, 2013, A1；[74] Angewandte Chemie - International Edition, 2013, vol.52, #36, p.9539-9543；[75] Angew. Chem., 2013, vol.125, #36, p.9718-9722；[76] Organic Process Research and Development, 2003, vol.7, #5, p.649-654；[77] Chemistry - A European Journal, 2014, vol.20, #13, p.3813-3824；[78] Patent: US2014/179668, 2014, A1；[79] Tetrahedron Asymmetry, 2017, vol.28, #1, p.175-180；[80] Patent: WO2009/158571, 2009, A1

路线3：

• 步骤：冰冷却下，向反式-4-羟基-L-脯氨酸的甲醇悬浮液中滴加乙酰氯，温热至室温后与亚硫酰氯混合，40℃搅拌4小时得产物。
• 条件：With thionyl chloride In methanol；40℃；4小时
• 产率：88%
• 参考文献：[1] Patent: US5317016, 1994, A