90259-31-7

2-Amino-6-methoxybenzoic acid (2.01 g) was dissolved in a mixed solution of acetic acid, hydrobromic acid (48% H2O), and water. The mixture was cooled in a saturated sodium chloride ice-water bath. While cooling, an aqueous solution of NaNO2 (1 equivalent) was slowly added dropwise to the reaction system. The mixture was then stirred at 0°C for 2.5–3 hours, and the resulting diazonium salt was cooled at 0°C. A solution of cuprous bromide (1 equivalent) in HBr (48% H2O, 0.5 mL per mmol CuBr) was added at room temperature. The mixture was stirred at 65°C for 2.5–3 hours. The mixture was diluted with water, and the reaction mixture was extracted three times with ethyl acetate. The organic layer was washed several times with brine and separated. The organic layer was dried with anhydrous sodium sulfate, and the sodium sulfate solid was removed by filtration. The filtrate was concentrated under vacuum to remove the solvent, yielding the target molecule, 2-bromo-6-methylbenzoic acid.

Figure 2. Synthetic route of bromo-6-methylbenzoic acid