反应详情

1-(2-Fluorophenyl)ethanone (15 g, 109 mmol) and (R)-2-methylpropane-2-sulfinamide (15.79 g, 130 mmol) were placed in a round bottom flask fitted with a reflux condenser. Tetrahydrofuran (90 ml) (dried over 4 Å MS) was added followed by Ti(OEt)4 (49.5 g, 217 mmol) and the resulting yellow solution was stirred at gentle reflux overnight. The reaction was allowed to cool to room temperature and concentrated under reduced pressure. The residue was dissolved in ethyl acetate (200 mL) and brine (100 mL) was added dropwise while stirring vigorously. The addition of brine resulted in immediate formation of copious amounts of a white precipitate. After 10 min stirring at room temperature the suspension was filtered through a plug of celite using ethyl acetate for elution. The filtrate was transferred to a separation funnel, the layers were separated, and the organic layer was washed with brine (150 mL). The organic layer was dried over MgSO4, filtered and concentrated under reduced pressure and was purified using a CombiFlash system (330 g SiO2, gradient elution; heptanes:ethyl acetate 100:0→70:30) to afford (R)—N-(1-(2-fluorophenyl)ethylidene)-2-methylpropane-2-sulfinamide (20.6 g, 70.8% yield) 1H NMR (600 MHz, CDCl3) δ 7.69 (t, J=7.1 Hz, 1H), 7.43 (dd, J=13.0, 6.0 Hz, 1H), 7.18 (td, J=7.7, 1.0 Hz, 1H), 7.11 (ddd, J=11.3, 8.3, 0.8 Hz, 1H), 2.78 (d, J=3.4 Hz, 3H), 1.32 (s, 9H).

1. customfitted with a reflux condenser
2. temperatureat gentle reflux overnight
3. concentrationconcentrated under reduced pressure
4. dissolutionThe residue was dissolved in ethyl acetate (200 mL)
5. additionbrine (100 mL) was added dropwise
6. stirringwhile stirring vigorously
7. additionThe addition of brine
8. customresulted in immediate formation of copious amounts of a white precipitate
9. stirringAfter 10 min stirring at room temperature the suspension
10. filtrationwas filtered through a plug of celite
11. washfor elution
12. customThe filtrate was transferred to a separation funnel
13. customthe layers were separated
14. washthe organic layer was washed with brine (150 mL)
15. dry with materialThe organic layer was dried over MgSO4
16. filtrationfiltered
17. concentrationconcentrated under reduced pressure
18. customwas purified
19. washa CombiFlash system (330 g SiO2, gradient elution; heptanes:ethyl acetate 100:0→70:30)