反应详情

A mixture of 1-(5-bromo-2-fluoropyridin-3-yl)ethanone (5a, synthesized according to procedures described in WO2009016460; 11 g, 50.5 mmol), (R)-2-methylpropane-2-sulfinamide (Ak Scientific, 12.23 g, 101 mmol) and titanium (IV) ethoxide (Aldrich, 26.1 ml, 126 mmol) in THF (100 mL) was heated to reflux for 2 h. The mixture was cooled to room temperature, and brine (200 mL) was added. The suspension was vigorously stirred for 10 min. The suspension was filtered through a pad of silica gel and the organic phase was separated. The aqueous phase was extracted with EtOAc. The combined organic layers were washed with brine, dried over Na2SO4 and concentrated under reduced pressure. The residue was purified by silica gel chromatography (gradient 0-20% EtOAc/hexanes) to afford the title compound as a bright yellow oil (16 g, 49.8 mmol, 99% yield). MS m/z=320.8 [M+H]+; Calculated for C11H14BrFN2OS: 320.0

1. temperaturewas heated
2. temperatureto reflux for 2 h
3. filtrationThe suspension was filtered through a pad of silica gel
4. customthe organic phase was separated
5. extractionThe aqueous phase was extracted with EtOAc
6. washThe combined organic layers were washed with brine
7. dry with materialdried over Na2SO4
8. concentrationconcentrated under reduced pressure
9. customThe residue was purified by silica gel chromatography (gradient 0-20% EtOAc/hexanes)