Hydrogen Bromide → HCID 22329485, compound

Participants

Reaction Conditions

Reaction Steps

4-Fluoro-3-(5-fluoropyridin-2-yl)phenylamine (1.2 g) was dissolved in 1,4-dioxane (4 ml) and 48% aqueous hydrobromic acid (30 ml). The solution was cooled to 0° C. A solution of sodium nitrite (478 mg) in water (6 ml) was added dropwise with stirring to maintain an internal temperature below 4° C. The mixture was then aged a further 1 h at 4° C. A solution of copper(I) bromide (2.58 g) in 48% aqueous hydrobromic acid (10 ml) was then added slowly to retain a reaction temperature below 5° C. The resulting mixture was then stirred at 5-10° C. for 1 h, ambient temperature for 0.5 h and then heated at 50° C. for 0.5 h. The mixture was then cooled to 4° C., and made basic by addition of 4 N aqueous sodium hydroxide (106 ml), followed by 30% aqueous ammonium hydroxide (40 ml). The mixture was extracted with ethyl acetate, the organic phase dried over anhydrous sodium sulfate, filtered and evaporated to dryness. The residue was chromatographed (silica gel, 70% CH2Cl2/isohexane) to afford 2-(5-bromo-2-fluorophenyl)-5-fluoropyridine: 1H NMR (400 MHz, DMSO) δ 8.74 (1H, dd, J 2, 1 Hz), 8.05 (1H, dd, J 7, 3 Hz), 7.90 (2H, m), 7.69 (1H, m), 7.38 (1H, dd, J 11, 9 Hz); MS (ES+) m/z 270, 272.

Provenance & Evidence