4-Butoxy-3-fluorophenylboronic acid (T-9) was synthesized as follows: 4-bromo-1-butoxy-2-fluorobenzene (T-8) (97.5 g) prepared in the previous step was dissolved in dry tetrahydrofuran (THF) (500 ml) and the solution was cooled to -70 °C. Under nitrogen protection, n-butyllithium (n-BuLi) (241 ml) was slowly added dropwise with continuous stirring for 2 h at a maintained temperature of -70°C. Subsequently, a dry THF solution of trimethyl borate (62.4 g) was slowly added dropwise to the reaction system at the same temperature. The reaction mixture was gradually warmed to room temperature and stirring was continued for 16 hours. After completion of the reaction, 2N hydrochloric acid (HCl) (200 ml) was added to the reaction mixture for acidification. The mixture was extracted with toluene and after separating the organic layer, it was washed sequentially with water and saturated saline and finally dried with anhydrous magnesium sulfate. The organic phase was concentrated under reduced pressure to give a light brown solid product. Purification by recrystallization (solvent ratio: heptane/toluene=4:1, v/v) gave the target compound 4-butoxy-3-fluorophenylboronic acid (T-9) as a colorless powder (54.8 g) in 66% yield.
