Triphenylphosphine → 2-Fluoro-5-[1-(2-fluoro-6-methoxyphenyl)ethoxy]-1-nitrobenzene

Participants

Reaction Steps

To a solution of 4-fluoro-3-nitrophenol (this compound was synthesized according to the procedure described in the International publication WO97/39064) (0.2 g), 1-(2-fluoro-6-methoxyphenyl)ethanol (0.22 g) and triphenylphosphine (0.4 g) in tetrahydrofuran (1.5 mL) was added diisopropyl azodicarboxylate (40% toluene solution, 0.84 mL) at room temperature, and the mixture was stirred at room temperature for 2 hours. The reaction mixture was concentrated under reduced pressure, and the residue was purified by column chromatography on silica gel (eluent: n-hexane−n-hexane/ethyl acetate=8/1) to give 2-fluoro-5-[1-(2-fluoro-6-methoxy -phenyl)ethoxy]-1-nitrobenzene (0.15 g). This material was dissolved in tetrahydrofuran (3 mL). To the solution were added methanol (3 mL), nickel (II) bromide (5 mg) and sodium borohydride (55 mg) under ice-cooling, and the mixture was stirred at the same temperature for 30 minutes. Then the mixture was stirred at room temperature for 30 minutes. The reaction mixture was diluted with ethyl acetate, and the resulting mixture was washed with a saturated aqueous sodium hydrogen carbonate solution, water and brine successively, and dried over anhydrous magnesium sulfate. The solvent was removed under reduced pressure, and the residue was purified by column chromatography on silica gel (eluent: n-hexane/ethyl acetate=3/1) to give the title compound (0.11 g).

Provenance & Evidence