Bromide ion → (2-(2,4-Difluorophenoxy)-5-(trifluoromethyl)phenyl)boronic acid

Participants

Reaction Conditions

Reaction Steps

To a suspension of magnesium (0.083 g, 3.42 mmol) in tetrahydrofuran (1.000 mL) was added 0.5 mL of a solution of example 34a (1.099 g, 3.11 mmol) in tetrahydrofuran (1.5 mL). The reaction mixture was warmed (about 40-50° C.) until reaction commenced. The remaining solution of starting bromide was added dropwise. The reaction mixture was stirred at ambient temperature for 1 hour. The resulting Grignard solution was added dropwise to a solution of trimethyl borate (0.696 mL, 6.23 mmol) in tetrahydrofuran (1.5 mL) at 0° C. The reaction mixture was stirred at ambient temperature. After 1 hour at ambient temperature, the reaction mixture was quenched with ice water and then neutralized with 2 M HCl. The mixture was extracted with ethyl acetate (3×). The combined organics were washed with saturated aqueous sodium chloride, dried over anhydrous sodium sulfate, filtered, and concentrated. The crude material was purified by flash chromatography (silica gel, 10-33% ethyl acetate/hexanes) to provide the title compound (0.650 g, 65.7% yield).

Provenance & Evidence