反応 #80646
ord-95775d212b1a4e538d645c2f826c107f
反応方程式
反応物
試薬
反応条件
後処理
- 1workup.STIRRINGthe reaction mixture was stirred at -78° C. for 1 hour
- 2温度the reaction mixture was warmed to room temperature
- 3workup.STIRRINGwas stirred overnight
- 4その他The reaction was quenched with 50 mL of 1N HCl
- 5抽出the aqueous phase was extracted with ethyl acetate (3×60 mL)
- 6洗浄The combined organic layers were washed with brine
- 7乾燥dried over MgSO4
- 8ろ過filtered
- 9濃縮concentrated
- 10その他The crude mixture was purified by chromatography on silica gel (ethyl acetate/hexane, 65:35)
実験手順
To a solution of diisopropylamine (0.7 mL, 0.005 mol) in 9 mL of dry THF was added butyllithium (BuLi) (2.83 mL of 1.62M solution in hexane, 4.6 mmol) at 0° C. The solution was stirred at this temperature for 5 minutes and cooled to -78° C. with a dry ice/isopropanol bath. A solution of 2-methyl-3-[1-[4-(methylsulfonyl)phenyl]-4-(trifluoromethyl)-1H-imidazol-2-yl]pyridine (Example 46) (1.46 g, 3.8 mmol) in 12 mL of dry THF was added over 10 minutes and the reaction mixture was stirred at -78° C. for 1 hour. (Iodomethyl)trimethylsilane (1.23 g, 57 mmol) was added dropwise and the reaction mixture was warmed to room temperature and was stirred overnight. The reaction was quenched with 50 mL of 1N HCl and the aqueous phase was extracted with ethyl acetate (3×60 mL). The combined organic layers were washed with brine, dried over MgSO4, filtered and concentrated. The crude mixture was purified by chromatography on silica gel (ethyl acetate/hexane, 65:35) to give 1.30 g of 2-methyl-3-[1-[4-[[2-(trimethylsilyl) ethyl]sulfonyl]phenyl]-4-(trifluoromethyl) -1H-imidazol-2-yl]pyridine as a white solid (74%): mp(DSC) 155°-157° C. Anal. Calc'd. for C21H24F3N3O2SSi: C, 53.94; H, 5.17; N, 8.99; S, 6.86. Found: C, 53.77; H, 4.94; N, 8.75; 6.98.