o-Fluoroacetophenone → (R)-N-(1-(2-fluorophenyl)ethylidene)-2-methylpropane-2-sulfinamide

Beteiligte Stoffe

Reaktionsschritte

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).

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