Réaction #80632

Équation de réaction

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

Rendement 12.4%

Solvants

tetrahydrofuran

water

Conditions de réaction

Traitement

1. 1
   Autrethe ice bath was removed
2. 2
   workup.STIRRINGthe solution was stirred for 2 hours
3. 3
   Autrewas recooled to 0° C.
4. 4
   workup.STIRRINGAfter stirring for 1 hour
5. 5
   Températurethe reaction was heated
6. 6
   Températureto reflux for 72 hours
7. 7
   workup.STIRRINGAfter stirring for 5 minutes
8. 8
   workup.STIRRINGthe mixture stirred for 24 hours
9. 9
   Extractionextracted with ether
10. 10
    SéchageThe ethereal layer was dried over sodium sulfate
11. 11
    Filtrationfiltered
12. 12
    Concentrationconcentrated
13. 13
    AutreThe crude solid (13.3 g) was chromatographed (silica gel, hexane/isopropanol, 7/3)

Mode opératoire

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.

Source