General procedure for the synthesis of methyl 3-bromo-5-(hydroxymethyl)benzoate from methyl 3-amino-5-(hydroxymethyl)benzoate: Methyl 3-amino-5-(hydroxymethyl)benzoate (2.4 g, 13.2 mmol) was dissolved in anhydrous acetonitrile (10 mL) and slowly added dropwise to a solution of acetonitrile (20 mL) containing copper(II) bromide (3.54 g, 15.8 mmol) and tert-butyl nitrite (2.24 mL, 18.9 mmol). (2.24 mL, 18.9 mmol) in acetonitrile (20 mL), and the reaction temperature was maintained at 65 °C. The reaction mixture was stirred at 65 °C. The reaction mixture was stirred at 65 °C for 30 min, then cooled to room temperature and subsequently poured into 1N hydrochloric acid solution and extracted with ether. The organic layers were combined, washed with brine (2 times), dried over anhydrous sodium sulfate and concentrated. Purification by silica gel column chromatography (eluent: 30% ethyl acetate/hexane) afforded the target product methyl 3-bromo-5-(hydroxymethyl)benzoate 2.0 g in 62% yield. The product was identified by 1H-NMR (CDCl3, 300 MHz): δ 8.04 (s, 1H), 7.90 (s, 1H), 7.69 (s, 1H), 4.70 (s, 2H), 3.89 (s, 3H). Mass spectrometry analysis showed a molecular ion peak of 246.98 (MH)+.
