170230-88-3

121-43-7

7697-26-9

170230-88-3

To a 500 mL three-necked round-bottomed flask equipped with two dropping funnels and an argon inlet, 3-bromo-4-methylbenzoic acid (11.00 g, 51.2 mmol) and anhydrous THF (150 mL) were added under argon protection and stirred until complete dissolution. The reaction system was cooled to -78 °C and n-butyllithium (1.6 M hexane solution, 60.7 mL, 97.0 mmol) was slowly added dropwise through a dropping funnel. After the dropwise addition, the reaction continued to be stirred at -78 °C for 1 hour. Subsequently, trimethyl borate (17.7 mL, 159.0 mmol) was slowly added through a second dropping funnel. After addition, the reaction was maintained at -78 °C for 1 h. The reaction was slowly warmed to room temperature and stirred overnight. After completion of the reaction, the solvent was removed by distillation under reduced pressure. The crude product was dissolved in ether and poured into 1N HCl aqueous solution. The aqueous phase was extracted with ether (3 x 150 mL), the organic phases were combined, washed with saturated brine, dried over anhydrous magnesium sulfate, filtered and concentrated to dryness. The crude product was purified by ISCO system (220 g silica gel column, hexane/ethyl acetate gradient elution followed by dichloromethane/methanol gradient elution). Impurities were eluted in hexane/ethyl acetate and the pure product was eluted in a methanol/dichloromethane (5:95) solvent system to afford the target product 5-carboxylic acid-2-methylphenylboronic acid (3.3 g, 33% yield). The product was characterized by 1H NMR (400 MHz, acetone-d6): δ 12.10 (br s, 1H), 8.16 (s, 1H), 7.90-7.63 (m, 1H), 7.11 (d, J=7.9 Hz, 1H), 2.42 (s, 3H).