Synthesis
5-Bromo-2-amino-6-methylpyridine hydrobromide (29.4 kg, purity 76.5 wt%, 84 mol, 1.00 eq.) was dissolved in 48% hydrobromic acid (162.0 kg, 961 mol, 11.44 eq.) at a temperature below 35 °C. The resulting solution was cooled to 2 °C and bromine (43.0 kg, 269 mol, 3.20 eq.) was slowly added over 40 min. Subsequently, a 40 wt% aqueous sodium nitrite solution (28.9 kg, 419 mol, 4.99 eq.) was added dropwise over 50 min at a temperature range of -1 to 5 °C. The reaction mixture was kept at this temperature for 1 h. The pH was then adjusted to 13.1 with 50% aqueous sodium hydroxide solution (120.0 kg). the reaction solution was slowly warmed to 20 °C over 1 h and toluene (78.0 kg) was added. The mixture was stirred for 30 minutes and left to stand overnight. The clarified organic phase was obtained by filtration and washed twice with saturated aqueous sodium chloride solution (51.1 kg). A final 96.0 kg solution of 2,5-dibromo-6-methylpyridine (concentration 17.3 wt%) was obtained in 79% yield.
