反应详情

温度

0 °C

To a solution of 4-(5-hydroxymethyl-imidazol-1-yl)-3,3-dimethyl-isochroman-1-one (0.158 g, 0.574 mmol) (Example 6d) in dichloromethane (7 mL) at 0° C. under nitrogen is added DAST (0.487 g, 2.872 mmol) dropwise. The mixture is stirred at 0° C. overnight. After dilution with dichloromethane, the organic phase is washed twice with saturated aqueous sodium bicarbonate, water and brine. The combined aqueous phase is back-extracted once with dichloromethane. The combined organic phase is dried over magnesium sulfate and filtered through a cotton plug. The residue is purified by silica gel flash chromatography (elution with dichloromethane-methanol, 99:1 to 49:1) to afford 4-(5-fluoromethyl-imidazol-1-yl)-3,3-dimethyl-isochroman-1-one as a white solid; MS (ESI) m/z 275.0 (M+H); 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.31 (s, 3 H), 1.57 (s, 3 H), 5.27 (s, 1 H), 5.45 (dd, J=22.7, 12.4 Hz, 1 H), 5.58 (dd, J=21.2, 12.4 Hz, 1 H), 7.21 (d, J=5.3 Hz, 1 H), 7.29 (d, J=7.3 Hz, 1 H), 7.38 (d, J=2.8 Hz, 1 H), 7.55-7.61 (m, 1 H), 7.65 (dd, J=7.6, 1.5 Hz, 1 H), 8.27 (dd, J=7.7, 1.4 Hz, 1 H).

1. washAfter dilution with dichloromethane, the organic phase is washed twice with saturated aqueous sodium bicarbonate, water and brine
2. extractionThe combined aqueous phase is back-extracted once with dichloromethane
3. dry with materialThe combined organic phase is dried over magnesium sulfate
4. filtrationfiltered through a cotton plug
5. customThe residue is purified by silica gel flash chromatography (elution with dichloromethane-methanol, 99:1 to 49:1)