General procedure for the synthesis of 2-bromo-5-hydroxypyrazine from 2-amino-5-bromopyrazine: sodium nitrite (1.35 g, 19.53 mmol) was added to concentrated sulfuric acid (9.8 mL) in batches at 0 °C. The mixture was heated to 50 °C until the sodium nitrite was completely dissolved and subsequently cooled to 0 °C. A solution of 5-bromo-pyrazin-2-ylamine (2.57 g, 14.68 mmol) in concentrated sulfuric acid (14.7 mL) was added slowly and dropwise. The ice bath was removed and the mixture was gradually warmed to room temperature and stirred for 15 minutes, followed by heating to 45 °C for 7 minutes. Upon completion of the reaction, it was cooled to room temperature and the reaction mixture was slowly poured into crushed ice water (100 mL). The pH of the aqueous phase was adjusted to 4 with 20% aqueous sodium hydroxide, followed by extraction with ethyl acetate (3 x 100 mL). The organic phases were combined, washed with water (50 mL), dried over anhydrous magnesium sulfate, filtered and concentrated to give 2-bromo-5-hydroxypyrazine (1.88 g, 73% yield) as a yellow solid. The product was characterized by 1H NMR (CDCl3, 300 MHz): δ 8.07 (1H, s), 7.62 (1H, d, J=3.0 Hz).
