General procedure for the synthesis of 4-fluoro-3-nitrophenylboronic acid from 4-fluorophenylboronic acid: fuming nitric acid (140 mL) was added to a 250 mL four-necked flask and cooled in a dry ethanol bath to a temperature of between -35 °C and -45 °C with continuous stirring. Pre-thoroughly dried and pulverized 4-fluorophenylboronic acid (20 g) was slowly added to the flask in batches, ensuring that the reaction temperature was maintained between -35 °C and -45 °C. The reaction temperature was then adjusted to the temperature of the flask. After the addition was completed, the progress of the reaction was monitored by thin layer chromatography (TLC) until the reaction was complete. The reaction mixture was poured into 200 g of crushed ice and stirred rapidly to precipitate a yellow solid, which was subsequently filtered through a Brinell funnel and washed twice with ice water (20 mL) and drained. The pH of the filtrate was adjusted to 6 with sodium bicarbonate solution and then extracted with ethyl acetate. The organic phases were combined, dried with anhydrous magnesium sulfate and concentrated to dryness. Finally, pulping with n-heptane gave the light yellow solid product 4-fluoro-3-nitrophenylboronic acid (8.3 g) in 31.5% yield.
