Example 58A; Synthesis of 2,6-difluoro-4-methoxyaniline; 10 g (56 mmol) of 1,3,5-trifluoro-2-nitrobenzene was dissolved in 250 mL of methanol, and a methanolic solution of 3.36 g (62 mmol) of sodium methanolate (250 mL) was added slowly and dropwise. The reaction mixture was stirred at room temperature overnight. Upon completion of the reaction, the solvent was removed by concentration under reduced pressure by rotary evaporator and the residue was hydrolyzed with dilute aqueous hydrochloric acid solution followed by extraction with ethyl acetate. The organic phases were combined, dried over anhydrous sodium sulfate and filtered to give the crude product. The crude product was dissolved in 110 mL of methanol, 275 mg of 10% palladium carbon catalyst was added and the hydrogenation reaction was carried out at room temperature overnight. After the reaction, the catalyst was removed by diatomaceous earth filtration, and the filtrate was concentrated under reduced pressure and purified by silica gel column chromatography (eluent: cyclohexane/ethyl acetate, v/v/v/9:1), resulting in 1.24 g of the target product 2,6-difluoro-4-methoxyaniline in 14% yield. The product was characterized by 1H-NMR (300 MHz, DMSO-d6): δ=3.66 (s, 3H, OCH3), 4.60 (br.s, 2H, NH2), 6.55-6.70 (m, 2H, ArH).
