Synthesis
The general procedure for the synthesis of 2,6-difluorophenylboronic acid from trimethyl borate and 1,3-difluorobenzene was as follows: 22.8 g of 1,3-difluorobenzene (Compound I) and 150 mL of anhydrous ethyl ether were added to a 500 mL dry reaction flask under nitrogen protection and the system was cooled to -78 °C. Slowly 187 mL of 1.6 M n-butyllithium hexane solution was added dropwise to the mixture. After the dropwise addition was completed, the reaction was stirred at -60 to -70 °C for 2 hours. The system was again cooled to -78°C and 60 g of trimethyl borate was slowly added dropwise, and after the dropwise addition was completed, the reaction was stirred at a controlled temperature of -50 to -60°C for 2 hours. The reaction mixture was slowly warmed to room temperature, the reaction was quenched by the addition of 200 mL of water and acidified with 36% hydrochloric acid. After recovering the organic solvent by ascending distillation, the reaction mixture was stirred at 70 to 80 °C for 6 hours. Finally, the system was cooled to crystallization, filtered and washed with cold water to afford 27.0 g of 2,6-difluorophenylboronic acid (Compound II).
