Water → 5-Fluoro-2-(2,3-difluoro-6-methoxybenzylamino)-4-nitroanisole

To a suspension of 4-fluoro-2-methoxy-5-nitroaniline (0.37 g) and potassium carbonate (0.36 g) in N,N-dimethylformamide (10 mL) was added 2,3-difluoro-6-methoxybenzyl-bromide (0.47 g), and the mixture was stirred at room temperature for 3 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=4/1) to give 5-fluoro-2-(2,3-difluoro-6-methoxybenzylamino)-4-nitroanisole (0.32 g). This material was dissolved in N,N-dimethylformamide (9.3 mL). To the solution were added sodium hydride (55%, 45 mg) and methyl iodide (0.18 mL) under ice-cooling, and the mixture was stirred at room temperature overnight. The reaction mixture was poured into water, and the resulting mixture was extracted with ethyl acetate. The extract was washed with water twice and brine, and dried over anhydrous magnesium sulfate. The solvent was removed under reduced pressure, and the residue was dissolved in methanol (4 mL)-tetrahydrofuran (4 mL). To the solution were added nickel(II) bromide (11 mg) and sodium borohydride (0.11 g) under ice-cooling, and the mixture was stirred at the same temperature for 30 minutes, and then stirred at room temperature for 30 minutes. The reaction mixture was poured into a saturated aqueous sodium hydrogen carbonate solution, 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=1/1) to give the title compound (0.17 g).

1. extractionthe resulting mixture was extracted with ethyl acetate
2. washThe extract was washed with water and brine
3. dry with materialdried over anhydrous magnesium sulfate
4. customThe solvent was removed under reduced pressure
5. customthe residue was purified by column chromatography on silica gel (eluent: n-hexane/ethyl acetate=4/1)

ORDレコード

ord-769b9e61771e439b9c9413e51828167d

出典データセット

uspto-grants-2013_04

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US08426427B2