184046-78-4 (2S,3S)-1-(叔丁氧基羰基)-3-羟基-吡咯烷-2-甲酸甲酯

作为医药中间体，用于相关药物合成。

医药

路线1：

• 步骤：将（3S）-3-羟基-L-脯氨酸甲酯盐酸盐溶于四氢呋喃和水，加入碳酸氢钠，滴加二碳酸二叔丁酯的四氢呋喃溶液，室温搅拌过夜；减压浓缩后水层用乙酸乙酯萃取，合并有机层洗涤、干燥、浓缩，硅胶色谱纯化得产物。
• 条件：With sodium hydrogencarbonate In tetrahydrofuran; water at 0 - 20℃; Inert atmosphere; Cooling with ice bath
• 收率：97%
• 参考文献：[1] Patent: WO2009/137130, 2009, A2. Location in patent: Page/Page column 146-147 [2] Journal of Medicinal Chemistry, 2006, vol. 49, #26, p. 7596 - 7599 [3] Patent: WO2005/32468, 2005, A2. Location in patent: Page/Page column 158; 179 [4] Patent: WO2005/32468, 2005, A2. Location in patent: Page/Page column 158; 179 [5] Journal of Medicinal Chemistry, 2007, vol. 50, #13, p. 3015 - 3025 [6] Patent: US2005/197359, 2005, A1. Location in patent: Page/Page column 17 [7] European Journal of Organic Chemistry, 2009, #20, p. 3368 - 3386 [8] Patent: WO2005/121135, 2005, A1. Location in patent: Page/Page column 190-191

路线2：

• 步骤：将含有3-羟基-吡咯烷-1,2-二羧酸1-叔丁酯的DMF溶液冷却至0℃，加入K₂CO₃，滴加碘甲烷，升温至环境温度，90℃加热1小时，冷却后用盐水稀释，乙醚萃取，干燥浓缩得产物。
• 条件：With potassium carbonate In N,N-dimethyl-formamide at 0 - 90℃; for 2 h;
• 收率：87%
• 参考文献：[1] Patent: US2008/20986, 2008, A1. Location in patent: Page/Page column 16 [2] Patent: WO2009/94287, 2009, A1. Location in patent: Page/Page column 31 [3] Patent: WO2010/138496, 2010, A1. Location in patent: Page/Page column 38-39 [4] Patent: WO2011/68926, 2011, A1. Location in patent: Page/Page column 39-40 [5] Patent: WO2010/33531, 2010, A1. Location in patent: Page/Page column 66 [6] Patent: WO2010/138666, 2010, A1. Location in patent: Page/Page column 99-100 [7] Patent: WO2008/24725, 2008, A1. Location in patent: Page/Page column 131 [8] Journal of Organic Chemistry, 2009, vol. 74, #10, p. 3735 - 3743 [9] Patent: US2015/152068, 2015, A1. Location in patent: Paragraph 0369; 0370; 0371 [10] Patent: WO2015/79417, 2015, A1. Location in patent: Page/Page column 77; 78 [11] Patent: WO2016/164580, 2016, A1. Location in patent: Page/Page column 280; 281