The general procedure for the synthesis of (4-cyano-3-methoxyphenyl)boronic acid from 2-methoxy-4-bromobenzonitrile was as follows: an overhead mechanical stirrer and a nitrogen inlet tube were assembled in a 1L three-necked round-bottomed flask. To the reaction flask was added 45.56 g (215 mmol) of 4-bromo-2-methoxybenzonitrile, 64 mL (277 mmol) of triisopropyl borate, and 500 mL of anhydrous THF.The reaction system was cooled to -78 °C in a dry ice/acetone bath. A n-butyllithium solution (2.5 M in hexane, 110 mL, 275 mmol) was slowly added dropwise through a constant pressure dropping funnel. After dropwise addition, the reaction was maintained at -78 °C with continued stirring for 30 min, followed by addition of 2N hydrochloric acid solution to quench the reaction. The reaction mixture was stirred at room temperature for 1 h and then poured into ice water. The aqueous phase was extracted three times with ether (Et2O). The organic phases were combined and back-extracted with 1N sodium hydroxide solution. The alkaline aqueous phase was washed with ether and acidified with concentrated hydrochloric acid to pH < 2. The acidified aqueous phase was again extracted with ether. The organic phases were combined, dried with anhydrous magnesium sulfate, filtered and concentrated under reduced pressure to give 20.77 g (55% yield) of the target product (4-cyano-3-methoxyphenyl)boronic acid as a white solid. The product was characterized by 1H NMR (500 MHz, d6-DMSO): δ 7.68 (d, J=8.0 Hz, 1H), 7.59 (s, 1H), 7.47 (d, J=8.0 Hz, 1H), 3.95 (s, 3H).
