反応 #80614

反応方程式

sodium acetate

2-(3-chloro-4-methylphenyl) -1-[4-(methylsulfonyl)phenyl]-4-(trifluoromethyl)-1H-imidazole

2-(3-chloro-4-methylphenyl)-1-[4-(methylsulfonyl)phenyl]-4-(trifluoromethyl)-1H-imidazole

n-BuMgCl

hydroxylamine-O-sulfonic acid

triethylborane

→

4-[2-(3-chloro-4-methylphenyl)-4-(trifluoromethyl)-1H-imidazol-1-yl]benzenesulfonamide

収率 36.1%

溶媒

tetrahydrofuran

water

反応条件

後処理

1. 1
   その他ice bath was removed
2. 2
   workup.STIRRINGsolution stirred for 1 hour
3. 3
   workup.STIRRINGAfter stirring for 2 hours
4. 4
   温度the reaction was heated
5. 5
   温度to reflux for 72 hours
6. 6
   温度The reaction mixture was cooled to room temperature
7. 7
   workup.STIRRINGAfter stirring for 5 minutes
8. 8
   workup.STIRRINGthe mixture stirred for 20 hours
9. 9
   抽出extracted with ether (2×250)
10. 10
    乾燥The ethereal layer was dried over sodium sulfate
11. 11
    ろ過filtered
12. 12
    濃縮concentrated in vacuo
13. 13
    その他The crude product (710 mg) was chromatographed (silica gel, ethyl acetate/toluene 3/7)

実験手順

To a clear solution of 2-(3-chloro-4-methylphenyl) -1-[4-(methylsulfonyl)phenyl]-4-(trifluoromethyl)-1H-imidazole (Example 16) (500 mg, 1.2 mmol) in tetrahydrofuran (10 mL) at 0° C., n-BuMgCl (2M solution in THF, 2.4 mL, 4.8 mmol) was added over 10 minutes. After stirring for additional 10 minutes, ice bath was removed and solution stirred for 1 hour. The reaction mixture was re-cooled to 0° C. and triethylborane (1M solution in THF, 6 mL, 6 mmol) was added. After stirring for 2 hours, the reaction was heated to reflux for 72 hours. The reaction mixture was cooled to room temperature and treated with aqueous sodium acetate (1 g in 4 mL water). After stirring for 5 minutes, solid hydroxylamine-O-sulfonic acid (1 g) was added and the mixture stirred for 20 hours. The reaction mixture was diluted with water and extracted with ether (2×250). The ethereal layer was dried over sodium sulfate, filtered and concentrated in vacuo. The crude product (710 mg) was chromatographed (silica gel, ethyl acetate/toluene 3/7) to give pure 4-[2-(3-chloro-4-methylphenyl)-4-(trifluoromethyl)-1H-imidazol-1-yl]benzenesulfonamide (180 mg, 36%) as a white solid: mp(DSC) 222° C. Anal. Calc'd. for C17H13N3SO2F3Cl: C, 49.10, H, 3.15, N, 10.11. Found: C, 49.42, H, 3.19, N, 9.75.

出典