Hydrochloric Acid → (4-Acetyl-2-fluorophenyl)boronic acid

Participants

Reaction Conditions

Reaction Steps

Methylmagnesium chloride (3 M in toluene/tetrahydrofuran) (2.54 mL, 7.6 mmol) was added to a 0° C. solution of 4-bromo-3-fluoro-N-methoxy-N-methylbenzamide (500 mg, 1.9 mmol) in tetrahydrofuran (10 mL). After stirring at 0° C. for 30 min, the reaction mixture was cooled to −78° C. and n-butyllithium (2.6 mL, 4.2 mmol) was added. After stirring at −78° C. for 2 h, triisopropylborate (1.5 mL, 6.7 mmol) was added and the reaction allowed to warm slowly to ambient temperature over 3 h. 1 M hydrochloric acid (5 mL) was added and the reaction stirred for 10 min. The reaction mixture was concentrated in vacuo to remove tetrahydrofuran, saturated with sodium chloride and extracted with diethyl ether. Combined ethereal extracts were extracted with 0.5 N aqueous sodium hydroxide (6×5 mL). Combined extracts were acidified, saturated with sodium chloride and reextracted with ethyl acetate. The combined extracts were washed with brine, dried (sodium sulfate) and concentrated in vacuo to afford (4-acetyl-2-fluorophenyl)boronic acid which was used in the subsequent step without further purification.

Provenance & Evidence