263400-88-0 4-甲基苯磺酸3-(甲基磺酰基)丙酯

4-甲基苯磺酸3-(甲基磺酰基)丙酯可作为有机合成中间体和医药中间体，主要用于实验室研发过程和化工生产过程中。

医药; 有机合成

路线1：

• 步骤: 将4-甲基苯-1-磺酰氯（759mg，3.98mmol）、3-（甲基磺酰基）丙-1-醇（500mg，3.62mmol）和三乙胺（0.555mL，3.98mmol）溶解在二氯甲烷（5mL）中，氮气氛围下搅拌12小时；减压除溶剂，半制备HPLC-UV纯化得产物（881mg，83%收率）。
• 条件: 三乙胺；二氯甲烷；12h；氮气氛
• 收率: 83%
• 参考文献: [1] Patent: WO2018/29150, 2018, A1. Location in patent: Page/Page column 37-38 [2] Patent: WO2013/144098, 2013, A1. Location in patent: Page/Page column 96 [3] Patent: WO2015/89809, 2015, A1. Location in patent: Page/Page column 62 [4] Patent: WO2015/95256, 2015, A1. Location in patent: Page/Page column 62; 63 [5] Patent: WO2017/13046, 2017, A1. Location in patent: Page/Page column 34-35

路线2：

• 步骤: 向0℃的16A（2.16g，8.31mmol）的MeOH（44mL）溶液中加入OXONE（10.2g，16.6mmol）的水（44mL）溶液，冰浴升温至室温搅拌3小时；减压除MeOH，水稀释后用EtOAc萃取，合并有机层洗涤、干燥、浓缩得产物（2.39g，98%收率）。
• 条件: Oxone；甲醇-水；0-20℃；3h
• 收率: 98%
• 参考文献: [1] Patent: WO2015/171722, 2015, A1. Location in patent: Page/Page column 102 [2] Patent: WO2007/18314, 2007, A2. Location in patent: Page/Page column 221-222 [3] Patent: WO2008/1931, 2008, A2. Location in patent: Page/Page column 79-80 [4] Journal of Medicinal Chemistry, 2012, vol. 55, # 8, p. 3960 - 3974 [5] Patent: WO2016/57731, 2016, A1. Location in patent: Page/Page column 97 [6] Patent: US2017/290800, 2017, A1. Location in patent: Page/Page column 0473 [7] Patent: US2017/291908, 2017, A1. Location in patent: Paragraph 0472 [8] Patent: CN108003074, 2018, A. Location in patent: Paragraph 0117; 0118; 0121; 0122 [9] Patent: WO2006/46031, 2006, A1. Location in patent: Page/Page column 79-80 [10] Patent: WO2012/111849, 2012, A1. Location in patent: Page/Page column 153 [11] Patent: WO2014/22528, 2014, A1. Location in patent: Page/Page column 94; 95 [12] Patent: WO2014/19186, 2014, A1. Location in patent: Page/Page column 80; 81 [13] Patent: WO2015/24526, 2015, A1. Location in patent: Page/Page column 30 [14] Patent: WO2015/51496, 2015, A1. Location in patent: Page/Page column 74; 75 [15] Patent: WO2015/51725, 2015, A1. Location in patent: Page/Page column 72; 73 [16] Patent: US2016/24063, 2016, A1. Location in patent: Paragraph 0286-0288 [17] Patent: CN103030646, 2016, B. Location in patent: Paragraph 0477; 0479-0482 [18] Patent: WO2016/177655, 2016, A1. Location in patent: Page/Page column 108 [19] European Journal of Medicinal Chemistry, 2017, vol. 138, p. 1147 - 1157 [20] Patent: EP3207928, 2017, A2. Location in patent: Paragraph 0180-0182

路线3：

• 步骤: 3-甲硫基-丙醇（5.3g，50mmol）、三乙胺（13.9mL，100mmol）、DMAP（1.2g，10mmol）溶于150mL二氯甲烷，分批加入甲苯磺酰氯（14.3g，75mmol），20℃搅拌3h；反应液用1N盐酸、水、饱和盐水洗涤，干燥浓缩得粗产物；粗产物溶于100mL二氯甲烷，0℃滴加77% mCPBA（17.3g，77.1mmol）的二氯甲烷溶液，自然升温至20℃搅拌2h；抽滤除固体，洗涤、干燥、浓缩，快速柱色谱纯化得产物（12.0g，两步收率82%）。
• 条件: 阶段1：dmap、三乙胺、二氯甲烷、20℃、3h；阶段2：3-氯-苯甲酰过氧酸、二氯甲烷-水、20℃、2h
• 收率: 82%
• 参考文献: [1] Patent: CN103145663, 2016, B. Location in patent: Paragraph 0103-0105