General procedure for the synthesis of methyl 6-bromo-3-methoxy-2-methylbenzoate from 6-bromo-3-methoxy-2-methylbenzoic acid and methanol: 6-bromo-3-methoxy-2-methylbenzoic acid (1.0 g, 4.08 mmol, 1.00 eq.) was placed in a 50 mL round-bottomed flask, and dichloromethane (20 mL) was added as solvent. Subsequently, N,N-diisopropylethylamine (DIEA, 1.32 g, 10.21 mmol, 2.50 eq.), 1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium 3-oxide hexafluorophosphate (HATU, 1.87 g, 4.92 mmol, 1.20 eq.) and methanol (2 mL). The reaction mixture was stirred at room temperature for 4 hours. After completion of the reaction, the solvent was removed by distillation under reduced pressure and the crude product obtained was purified by silica gel column chromatography with the eluent ethyl acetate/petroleum ether (1/1, v/v). Finally, 1.03 g of methyl 6-bromo-3-methoxy-2-methylbenzoate was obtained in 97% yield as a white solid.
