Sodium Hydroxide → 4-(4-Fluorotetrahydro-2H-pyran-4-yl)benzonitrile

Participants

Reaction Steps

To a suspension of 4-(4-hydroxytetrahydro-2H-pyran-4-yl)benzonitrile (Step 1 of Intermediate 1,300 mg, 1.48 mmol) in dichloromethane (28 mL) was added dropwise N-ethyl-N-(trifluoro-λ4-sulfanyl)ethanamine (586 mg, 1.77 mmol, dissolved in 2 mL dichloromethane) at a temperature of −78° C. After 30 minutes at this temperature, the reaction mixture was rapidly warmed to −20° C. by the aid of a water/ice bath for no longer than 30 seconds whereupon NaOH (1N aq., 10 mL) was added and the reaction mixture was allowed to warm to rt. The mixture was diluted with water (100 mL) and extracted with diethyl ether. The organic extract was dried with anhydrous magnesium sulfate and filtered. After evaporation of the solvent, the crude product was purified by MPLC (silica, cyclohexane/ethyl acetate 20:1→4:1) to afford the title compound in pure form (267 mg, 88%): 1H NMR (400 MHz, CDCl3) δ 7.68 (d, 2H), 7.50 (d, 2H), 3.98-3.83 (m, 4H), 2.23-2.05 (m, 2H), 1.91-1.85 (m, 2H).

Provenance & Evidence