反应 #80632

反应方程式

sodium acetate

solution

2-methyl-5-[1-[4-(methylsulfonyl)phenyl]-4-trifluoromethyl-1H-imidazol-2-yl]pyridine

n-BuMgCl

hydroxylamine-O-sulfonic acid

triethylborane

→

4-[2-(6-methylpyridin-3-yl)-4-(trifluoromethyl)-1H-imidazol-1-yl]benzenesulfonamide

收率 12.4%

溶剂

tetrahydrofuran

water

反应条件

后处理

1. 1
   其他the ice bath was removed
2. 2
   workup.STIRRINGthe solution was stirred for 2 hours
3. 3
   其他was recooled to 0° C.
4. 4
   workup.STIRRINGAfter stirring for 1 hour
5. 5
   温度the reaction was heated
6. 6
   温度to reflux for 72 hours
7. 7
   workup.STIRRINGAfter stirring for 5 minutes
8. 8
   workup.STIRRINGthe mixture stirred for 24 hours
9. 9
   萃取extracted with ether
10. 10
    干燥The ethereal layer was dried over sodium sulfate
11. 11
    过滤filtered
12. 12
    浓缩concentrated
13. 13
    其他The crude solid (13.3 g) was chromatographed (silica gel, hexane/isopropanol, 7/3)

实验过程

To a clear solution of Example 33 (2.4 g, 6.3 mmol) in tetrahydrofuran (60 ml) at 0° C., n-BuMgCl (2M solution in THF, 15.7 ml, 31.5 mmol) was added over 10 minutes. After stirring for additional 20 minutes, the ice bath was removed and the solution was stirred for 2 hours. The reaction mixture was recooled to 0° C. and triethylborane (1M solution in THF, 38 ml, 38 mmol) was added. After stirring for 1 hour, the reaction was heated to reflux for 72 hours. The reaction mixture was cooled to room temperature and treated with aqueous sodium acetate (5.5 g in 22 ml water). After stirring for 5 minutes, solid hydroxylamine-O-sulfonic acid (5.5 g) was added and the mixture stirred for 24 hours. The reaction mixture was diluted with water and extracted with ether. The ethereal layer was dried over sodium sulfate, filtered and concentrated. The crude solid (13.3 g) was chromatographed (silica gel, hexane/isopropanol, 7/3) to give 4-[2-(6-methylpyridin-3-yl)-4-(trifluoromethyl)-1H-imidazol-1-yl]benzenesulfonamide (298 mg, 12%): mp (DSC) 203° C. Anal. Calc'd. for C16H13N4SO2F3 0.25H2O: C, 49.68, H, 3.52 N, 14.48, S, 8.29. Found: C, 49.88, H, 3.39, N, 13.94, S, 8.47.

来源