Step d: Synthesis of 4-bromo-2,6-dichlorobenzoic acid
Aqueous sodium nitrite solution (3.64 g, 52 mmol, dissolved in 4 mL of water) was added dropwise to concentrated hydrochloric acid (15 mL) and cooled to -10°C to -5°C. 3-Amino-4-bromo-2,6-dichlorobenzoic acid (5 g, 17 mmol, product of step c) was added in batches to the above solution while controlling the reaction temperature to maintain it at about -5°C. The reaction mixture was stirred at this temperature for 2 hours. Subsequently, hypophosphorous acid (9 mL, 170 mmol) was added slowly and dropwise over 1 h at the same temperature. The reaction mixture was stirred at the same temperature for 3 hours and then transferred to a refrigerator and allowed to stand overnight. Precipitation generation was observed at this stage. The reaction mixture was slowly warmed up to room temperature and stirring was continued for 2 hours at room temperature. The reaction mixture was filtered and the resulting solid was washed with cold water and dried to afford 4-bromo-2,6-dichlorobenzoic acid as a pale yellow solid (2 g, 42% yield).1H NMR (400 MHz, MeOH-d4): δ 7.69 (s, 2H).
