反应详情

Into a 250-mL three neck round-bottom flask, which was purged and maintained with an inert atmosphere of nitrogen, was placed a solution of 4-(4-(trifluoromethyl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazol-2-yl)tetrahydro-2H-pyran-4-ol (compound 216.3, 2 g, 5.46 mmol) in tetrahydrofuran (100 mL). This was followed by the addition of sodium hydride (262 mg, 6.55 mmol, 60%) at −70° C. and stirred for 30 min. To this was added MeI (930 mg, 6.55 mmol). The resulting solution was stirred for 1 h at room temperature, then carefully quenched with 10 mL of water. The resulting mixture was diluted with 50 mL of brine. The aqueous phase was extracted with 2×50 mL of ethyl acetate. The combined organic layers were washed with 1×50 mL of brine, dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel chromatography with ethyl acetate/petroleum ether (1:3) as eluent to furnish 1.6 g (77%) of the title compound as light brown oil.

1. customInto a 250-mL three neck round-bottom flask, which was purged
2. temperaturemaintained with an inert atmosphere of nitrogen
3. stirringThe resulting solution was stirred for 1 h at room temperature
4. customcarefully quenched with 10 mL of water
5. additionThe resulting mixture was diluted with 50 mL of brine
6. extractionThe aqueous phase was extracted with 2×50 mL of ethyl acetate
7. washThe combined organic layers were washed with 1×50 mL of brine
8. dry with materialdried over anhydrous sodium sulfate
9. concentrationconcentrated under reduced pressure
10. customThe residue was purified by silica gel chromatography with ethyl acetate/petroleum ether (1:3) as eluent