反应详情

Cesium carbonate (1.90 g, 5.84 mmol) was added to a solution of the 3,5-difluoro-4-iodopyridin-2(1H)-one (1.0 g, 3.9 mmol) and ethyl (2R)-4-bromo-2-methyl-2-(methylsulfonyl)butanoate, T1, (1.45 g, 5.06 mmol) in tetrahydrofuran:t-butanol (1:1, 50 mL). The resulting suspension was heated to reflux and was stirred at this temperature for 72 h. The reaction was filtered through celite, and the filter pad was washed with EtOAc (3×50 mL). The combined filtrates were concentrated and the crude product was purified via flash chromatography on an Analogix SF15-24 g column using an eluent of EtOAc in hexanes (0-50%) to afford the title compound as a yellow solid (575.6 mg, 32%). MS (LCMS) m/z 463.9 (M+1). 1H NMR (400 MHz, DMSO-d6) δ ppm 1.23 (s, 3H) 1.58 (s, 3H) 2.20 (dt, J=13.90, 7.00 Hz, 1H) 2.52-2.62 (m, 1H) 3.14 (s, 3H) 4.00 (t, J=7.61 Hz, 2H) 4.05-4.22 (m, 2H) 7.94 (dd, J=4.20, 2.05 Hz, 1H).

1. temperatureThe resulting suspension was heated
2. temperatureto reflux
3. filtrationThe reaction was filtered through celite
4. washthe filter pad was washed with EtOAc (3×50 mL)
5. concentrationThe combined filtrates were concentrated
6. customthe crude product was purified via flash chromatography on an Analogix SF15-24 g column