Реакция #80646

Уравнение реакции

(Iodomethyl)trimethylsilane

2-methyl-3-[1-[4-(methylsulfonyl)phenyl]-4-(trifluoromethyl)-1H-imidazol-2-yl]pyridine

2-methyl-3-[1-[4-(methylsulfonyl)phenyl]-4(trifluoromethyl)-1H-imidazol-2-yl]pyridine

diisopropylamine

butyllithium

→

2-methyl-3-[1-[4-[[2-(trimethylsilyl) ethyl]sulfonyl]phenyl]-4-(trifluoromethyl) -1H-imidazol-2-yl]pyridine

Выход 74.0%

Растворители

THF

THF

Условия реакции

Обработка

1. 1
   workup.STIRRINGthe reaction mixture was stirred at -78° C. for 1 hour
2. 2
   Температураthe reaction mixture was warmed to room temperature
3. 3
   workup.STIRRINGwas stirred overnight
4. 4
   ДругоеThe reaction was quenched with 50 mL of 1N HCl
5. 5
   Экстракцияthe aqueous phase was extracted with ethyl acetate (3×60 mL)
6. 6
   ПромывкаThe combined organic layers were washed with brine
7. 7
   Сушкаdried over MgSO4
8. 8
   Фильтрацияfiltered
9. 9
   Концентрированиеconcentrated
10. 10
    ДругоеThe crude mixture was purified by chromatography on silica gel (ethyl acetate/hexane, 65:35)

Методика

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.

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