Step 2: A solution of bromine (773 μL, 15 mmol, dissolved in 15 mL of dichloromethane) was added dropwise to a solution of tert-butylamine (1.6 mL, 15 mmol) in dichloromethane (100 mL) at -78 °C. The reaction temperature of -78 °C was maintained and stirred for 30 min. Subsequently, a solution of methyl 3-hydroxy-2-methylbenzoate (2.5 g, 15 mmol, dissolved in 15 mL of dichloromethane) was added slowly and dropwise to the reaction mixture over a 30-minute period while maintaining the -78 °C condition. Upon completion of the reaction, the mixture was gradually warmed to room temperature and stirring was continued for 15 hours. The reaction mixture was washed sequentially with 20% aqueous citric acid and brine, and the organic phase was dried over anhydrous sodium sulfate. The drier was removed by filtration and the filtrate was concentrated under reduced pressure to give a brown residue. The residue was purified by silica gel column chromatography using 10% hexane solution of diethyl ether as eluent. The purified fractions were collected, combined and concentrated under reduced pressure to give 612 mg (2.5 mmol, 17% yield) of methyl 4-bromo-3-hydroxy-2-methylbenzoate as a colorless oil. The product was confirmed by 1H NMR (400 MHz, CDCl3): δ 7.37-7.29 (m, 2H), 5.71 (s, 1H), 3.81 (s, 3H), 2.53 (s, 3H). Mass spectrometry (EI) analysis was consistent with the molecular weight of C9H9BrO3: 245 (MH+).
