3-Bromo-2,4-difluorobenzenamine

A mixture of 2-bromo-1, 3-difluoro-4-nitrobenzene (30 g, 130 mmol) and tin (II) chloride dihydrate in 36percent hydrochloric acid (150 ml) was heated to 40°C. Diethyl ether (20 ml) was slowly added to bring about solution. Once in solution the reaction proceeded rapidly and the ether boiled away. After heating at 60°C for 1 h the reaction was cooled and then poured onto ice-water (1. 5 1). The solution was made basic (pH 13) with 30percent aq. sodium hydroxide keeping the internal temperature below 20°C. The resulting grey slurry was swirled with chloroform (2 x 500 ml), the organic extracts were combined, washed with water, dried over anhydrous magnesium sulfate containing 2 g decolourising charcoal, filtered and evaporated to dryness. Trituration with isohexane afforded 23 g (83percent) of the title compound as a buff-coloured solid: 1H NMR (360 MHz, CDCl3) 8 3.51 (2H, br), 6.65-6. 70 (1H, m), 6.75-6. 80 (1H, m).2-Bromo-1, 3-difluoro-4-nitrobenzene (Compound 5) (24 g, 100 mmol) was dissolved in 100 mL of concentrated hydrochloric acid and heatedTo 60 ° C, stannous chloride (68 g, 300 mmol) was added in portions and refluxed for 3 h.The reaction solution was poured into a large amount of crushed ice, and the pH was adjusted to 8 by adding sodium hydroxide, and the mixture was filtered under reduced pressure.The organic phase was combined, washed once with saturated brine, dried over anhydrous Na2SO.Column chromatography gave a solid 17 g (Yield: 82percent).3-Bromo-2, 4-difluoroaniline To a mixture of 2-bromo-1, 3-difluoro-4-nitrobenzene (5 g, 21.01 mmol), AcOH (5.70 g, 94.53 mmol), EtOH (100 mL) and HB. To a solution of A mixture of 106 2, 2-dimethyl-1, 3-dioxane-4, 6-dione (7.62 g, 52.88 mmol) in 107 trimethoxymethane (26.3 mL, 240.38 mmol) was heated at 85 C. and stirred for 1.5 h. 498 3-Bromo-2, 4-difluoroaniline (10 g, 48.08 mmol) in 33 ethanol (42.4 mL) was added and the reaction mixture was stirred at 85 C. for 3 h. The mixture was cooled with the resulting solid was filtered and washed with IPA (2×50 mL) and diethyl ether (4×50 mL). The solid was dried under vacuum overnight to afford 499 5-[(3-bromo-2, 4-difluoroanilino)methylidene]-2, 2-dimethyl-1, 3-dioxane-4, 6-dione (14.62 g, 84%) as a beige solid; 1H NMR (400 MHz, DMSO, 30 C.) 1.69 (6H, s), 7.33-7.43 (1H, m), 7.86-7.97 (1H, m), 8.56-8.64 (1H, m), 11.24 (1H, s); m/z: ES+ [M+H]+ 362.0.