(Diethylamino)sulfur trifluoride → 4-[5-(2-Fluoro-ethyl)-imidazol-1-yl]-3,3-dimethyl-isochroman-1-one

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Reaction Steps

To a partial suspension of 4-[5-(2-hydroxy-ethyl)-imidazol-1-yl]-3,3-dimethyl-isochroman-1-one (0.180 g, 0.616 mmol) (example 27f) in dichloromethane (10 mL) at 0° C. under nitrogen is added DAST (0.314 g, 1.848 mmol) dropwise. After 30 min, the mixture is diluted with dichloromethane and 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-(2-fluoro-ethyl)-imidazol-1-yl]-3,3-dimethyl-isochroman-1-one as an oil. The material is converted to the HCl salt and triturated with methanol, to give a crystalline solid; MS (ESI) m/z 289.0 (M+H); 1H NMR (400 MHz, MeOD) δ ppm 1.27 (s, 3 H), 1.59 (s, 3 H), 4.69-4.95 (m, 4 H), 5.73 (br. S., 1 H), 7.16 (s, 1 H), 7.53 (d, J=7.6 Hz, 1 H), 7.63 (br. S., 1 H), 7.71 (td, J=7.6, 1.1 Hz, 1 H), 7.81 (td, J=7.6, 1.3 Hz, 1H), 8.27 (dd, J=7.8, 1.3 Hz, 1 H).

Provenance & Evidence