Hydrochloric Acid → (2'-Cyano-2-fluoro-[1,1'-biphenyl]-3-yl)boronic acid

Participants

Reaction Conditions

Reaction Steps

A cooled (−78° C.) solution of n-butyllithium (11.7 ml of a 2.5M solution in hexanes, 29.1 mmol) in tetrahydrofuran (100 ml) was treated with 2,2,6,6-tetramethylpiperidine (5.16 ml) and stirring at −78° C. was continued for 15 min. The reaction was then treated with a cooled (0° C.) solution of 2′-fluorobiphenyl-2-carbonitrile (5.50 g) in tetrahydrofuran (15 ml) added dropwise over 10 min. This mixture was stirred at −78° C. for 2 h and then treated with trimethyl borate (6.30 ml) added dropwise over 5 min. The reaction was stirred at −78° C. for 10 min then allowed to warm to ambient temperature. 2N Hydrochloric acid (5 ml) was added and the mixture evaporated to dryness. The residue was stirred with 2N hydrochloric acid (95 ml) for 30 min and then extracted with diethyl ether (2×100 ml). The organics were combined, extracted with 2N sodium hydroxide (100 ml) and the organics discarded. The aqueous was cooled to 0° C. and made just acidic (pH 6) with 36% hydrochloric acid. After stirring at 0° C. for 1 h the resulting solid was collected by filtration and dried. Crystallisation from diethyl ether/isohexane afforded 2′-cyano-2-fluorobiphenyl-3-boronic acid as a yellow solid (4.50 g, 67%): δH (360 MHz, CDCl3) 5.23 (1H, s), 5.25 (1H, s), 7.33 (1H, m), 7.42-7.56 (3H, m), 7.65 (1H, m), 7.77 (1H, m), 7.93 (1H, m).

Provenance & Evidence