4,5-dibroMonicotinic acid

630-25-1

1009334-28-4

5-Bromonicotinic acid (25.25 g, 125 mmol) was dissolved in anhydrous tetrahydrofuran (500 mL) under nitrogen protection, stirred and cooled to -70 °C. Lithium diisopropylammonium (1.8 M, 144 mL, 260 mmol) was added slowly and dropwise over 1 hour. After the dropwise addition, the reaction mixture was continued to stir at -55 °C for 2.5 h, followed by cooling to -70 °C again. 1,2-Dibromotetrachloroethane (50 g, 154.5 mmol) was added in batches over 30 minutes. Once the addition was complete, stirring was continued for 30 minutes, followed by a slow warming to -20°C over 2 hours. After careful addition of water (150 mL), the organic solvent was removed by distillation under reduced pressure. The residue was diluted with water (500 mL) and washed with ethyl acetate. Subsequently, the aqueous phase was acidified with hydrochloric acid to pH 3.00. The precipitated solid product was collected by filtration and dried under vacuum at 60 °C to give 4,5-dibromonicotinic acid (14.2 g). The filtrate was extracted with ethyl acetate, the organic phases were combined, washed with water, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure to give additional 4,5-dibromonicotinic acid (18.6 g, total yield 32.8 g, 93% yield). The product was characterized by 1H NMR (DMSO-d6, 400 MHz): δ 8.92 (s, 1H), 8.73 (s, 1H).