Hydrochloric Acid → {4-[4-(Trifluoromethoxy)phenoxy]phenyl}boronic acid

Participants

Reaction Conditions

Reaction Steps

In a flame-dried 25 mL schlenk tube backfilled with argon (×3) a solution of 4-bromo-3-fluorophenol (0.346 g, 2 mmol) in N-methylpyrrolidine (8 mL) under an argon atmosphere was added 4-(trifluoromethoxy)iodobenzene (0.626 mL, 4 mmol), 2,2,6,6-tetramethylheptane-3,5-dione (0.092 mL, 0.44 mmol) and cesium carbonate (1.30 g, 4 mmol). The slurry was degassed by bubbling argon for 15 min and CuCl (0.099 g, 1 mmol) was then added. The reaction mixture was again degassed and then warmed to 100° C. for 7 h. After cooling to room temperature, Et2O (75 mL) was added slowly. The resulting slurry was filtered and the solid washed with Et2O (3×50 mL). The combined filtrates were washed with 2 M NaOH (100 mL), water (100 mL), 1 M aq HCl (100 mL), water (100 mL) and saturated brine (100 mL), the subsequently dried over Na2SO4 and concentrated under reduced pressure. The residue was purified via flash chromatography with 100% Hexane. This column was repeated three times combining the purest fractions each column to obtain pure material due to similarly eluting 4-(trifluoromethoxy)iodobenzene to afford 1-bromo-2-fluoro-4-(4-(trifluoromethoxy)phenoxy)benzene (0.15 g, 45%) as a colorless liquid. To a solution of 1-bromo-2-fluoro-4-(4-(trifluoromethoxy)phenoxy)benzene (2.1 mmol, 0.7 g) and triisopropyl borate (2.7 mmol, 0.63 mL) in dry THF (15 mL) at −78° C. was added dropwise 2.5M BuLi (6.5 mL) in Hexanes over 5 minutes. The reaction was stirred for 3 h at −78° C. at which point 10 mL of 6M HCl is added and the solution is allowed to warm up to room temperature and stir overnight. The reaction mixture was diluted with EtOAc (150 mL) and water (150 mL). The organic layer is taken separately and rinsed with water (150 mL), followed by brine (150 mL) and then dried over Na2SO4. The EtOAc is then concentrated in vacuo to afford a waxy solid which is then treated with 2M NaOH (40 mL) and stirred for 15 min diluted with water (300 mL) and stirred for 20 minutes. The solution is then filtered and the filtrate washed with hexane (3×100 mL). The aqueous layer was carefully acidified to pH 1 with 6 m HCl. The resulting white solid was filtered and dried on a high vacuum overnight to afford the titled compound in 67% yield.

Provenance & Evidence