Hydrochloric Acid → 5-Fluoro-2-methanesulfonylamino-4-nitroanisole

Participants

Reaction Steps

To a solution of 4-fluoro-2-methoxy-5-nitroaniline (0.16 g) and pyridine (0.21 mL) in tetrahydrofuran (3 mL) was added methanesulfonyl chloride (0.074 mL) under ice-cooling, and the mixture was stirred at room temperature for 3 hours, and then stirred at 50° C. overnight. The reaction mixture was poured into 1 mol/L hydrochloric acid, and the resulting mixture was extracted with ethyl acetate. The extract was washed with water and brine, 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=1/3) to give 5-fluoro-2-methanesulfonylamino-4-nitroanisole (0.1 g). This material was dissolved in N,N-dimethylformamide (3 mL). To the solution were added potassium carbonate (68 mg) and 2,3-difluoro-6-methoxybenzyl bromide (99 mg), and the mixture was stirred at room temperature for 2 hours. The reaction mixture was poured into water, and the resulting mixture was extracted with ethyl acetate. The extract was washed with water and brine, 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=½) to give 5-fluoro-2-[N-(2,3-difluoro-6-methoxybenzyl)-N-methanesulfonylamino]-4-nitroanisole (0.14 g). This material was dissolved in tetrahydrofuran (2 mL). To the solution was added 10% palladium-carbon powder (13 mg), and the mixture was stirred at room temperature under a hydrogen atmosphere overnight. The insoluble material was removed by filtration, and the filtrate was concentrated under reduced pressure. The residue was purified by column chromatography on silica gel (eluent: n-hexane/ethyl acetate=½) to give the title compound (80 mg).

Provenance & Evidence