반응 #80646
ord-95775d212b1a4e538d645c2f826c107f
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시약
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후처리
- 1workup.STIRRINGthe reaction mixture was stirred at -78° C. for 1 hour
- 2온도the reaction mixture was warmed to room temperature
- 3workup.STIRRINGwas stirred overnight
- 4기타The reaction was quenched with 50 mL of 1N HCl
- 5추출the aqueous phase was extracted with ethyl acetate (3×60 mL)
- 6세척The combined organic layers were washed with brine
- 7건조dried over MgSO4
- 8여과filtered
- 9농축concentrated
- 10기타The crude mixture was purified by chromatography on silica gel (ethyl acetate/hexane, 65:35)
실험 절차
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.