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 2.5 M solution in hexanes, 29.1 mmol) in THF (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 THF (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. 2 N Hydrochloric acid (5 ml) was added and the mixture evaporated to dryness. The residue was stirred with 2 N hydrochloric acid (95 ml) for 30 min and then extracted with diethyl ether (2×100 ml). The organics were combined, extracted with 2 N 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 4.50 g (67%) of the title compound as a yellow solid: 1H NMR (360 MHz, CDCl3) δ 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