General procedure for the synthesis of 2-methoxy-4-bromobenzoic acid from 2-hydroxy-4-bromobenzoic acid and iodomethane:
1. in a dry reaction flask, 2-hydroxy-4-bromobenzoic acid (1.2 g, 5.53 mmol) was dissolved in N,N-dimethylformamide (30 mL).
2. Potassium carbonate (2.3 g, 16.59 mmol) and iodomethane (861 μL, 13.83 mmol) were added to the above solution.
3. The reaction mixture was stirred at room temperature for 18 h. 4.
4. Upon completion of the reaction, the mixture was concentrated under vacuum to remove the solvent.
5. The residue was dissolved in ethyl acetate and washed with deionized water. 6.
6. The aqueous layer was separated and back-extracted with ethyl acetate (2×).
7. All organic layers were combined, washed with saturated brine and dried over anhydrous sodium sulfate.
8. After filtration to remove the desiccant, the filtrate was concentrated under vacuum to give 2-methoxy-4-bromobenzoic acid as an orange oil (1.27 g, 94% yield).
9. The product was characterized by 1H NMR (400 MHz, CDCl3) and LRMS APCI: 1H NMR δ 3.88 (s, 1H), 3.90 (s, 3H), 7.11-7.15 (m, 2H), 7.68 (d, 1H); LRMS APCI m/z 245/247 [M + H]+ .
