The general procedure for the synthesis of 2,6-difluoro-4-nitrophenol from 2,6-difluorophenol and ethyl acetate is as follows: with reference to Example 103, 2,6-difluorophenol (2.00 g) was dissolved in acetic acid (20 ml), and 60% nitric acid (1.20 ml) was slowly added dropwise under ice bath conditions. After the dropwise addition, the reaction mixture was stirred at room temperature for 1 hour. After completion of the reaction, the mixture was poured into ice water and extracted with ethyl acetate. The extract was washed with saturated saline and the organic layer was dried with anhydrous magnesium sulfate. The dried organic layer was filtered and the filtrate was concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography with the eluent being a mixed solvent with the volume ratio of hexane/ethyl acetate=3/1→2/1, resulting in the target compound 2,6-difluoro-4-nitrophenol (1.37 g, 51% yield) as a light yellow solid. The structure of the product was confirmed by 1H NMR (400 MHz, CDCl3), δppm: 7.95 (2H, m).
