磺酰胺的酸胺缩合：工艺案例
文摘
科学
2024-11-20 07:03
天津
- 磺酰胺的活性低于普通胺，不会和CDI反应产生脲，可以一锅法加料。
1eq.酸，1.1eq.磺酰胺，1.1eq.CDI，乙酸异丙酯5vol.加入反应釜，搅拌监控酸消耗完。加入1.6eq.DBU和0.05eq.CDI的2vol.乙酸异异丙酯溶液，25度搅拌，直到乙酰基咪唑中间体转化完。磷酸溶液洗涤，萃取，有机相浓缩，测含水，氯化氢气体成盐。总收率93%。Org. Process Res. Dev. 2020, 24, 1393−1404Org. Process Res. Dev. 2018, 22, 1393−14081,1′-Carbonyldiimidazole- (22.7 kg, 119 mol) was added to a stirred solution of 2-(6-methoxycarbonyl-1-methyl-1H-indol-3-yl)-2-(3,4-methylenedioxyphenyl)acetic acid 16 (39.8 kg, 108 mol) in dry tetrahydrofuran (398 L) at room temperature. The suspension was heated to reflux for 1.5 h, allowed to cool to room temperature, and treated sequentially with 2-methoxy-4- methylbenzenesulfonamide 5 (24 kg, 119 mol) and 1,8- diazabicyclo[5.4.0]undec-7-ene (DBU, 18.1 kg, 119 mol). The mixture was heated to reflux for 4.5 h, Organic Process Research & Development 2005, 9, 663−669- 第一阶段：乙酸乙酯为溶剂，1.2eq.CDI，40℃反应；
- 小编：酸和磺酰胺的CDI缩合法，一般选择THF为溶剂，DBU催化，该反应DBU催化效果不好的原因可能和四元含氮环有关。
Org. Process Res. Dev. 2019, 23, 1829−1840
