Triisopropyl borate → 4-Methylpyridine-3-Boronic Acid

Participants

Reaction Conditions

Reaction Steps

To a stirring solution of 3-bromo-4-methylpyridine (5.9 g, 34.3 mmol) in toluene (30 mL) and THF (7.5 mL) was added triisopropyl borate (10.3 mL, 44.6 mmol). The resulting mixture was cooled to −78° C. under a nitrogen atmosphere followed by the addition of n-butyllithium (17.83 mL, 44.6 mmol, 2.5 M in hexanes) over a period of 1 hour. The reaction mixture was allowed to stir for an additional 30 min and then the dry ice bath was removed. The reaction mixture was quenched by the addition of 2N HCl (60 mL). Upon reaching room temperature, the resulting yellow solution was transferred to a 500 mL separatory funnel and the layers were separated. The aqueous layer was neutralized to pH 7.0 with sodium hydroxide and then extracted with THF (3×60 mL). The combined organics were washed with brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The resulting solid material was vigorously stirred with acetonitrile and filtered to yield Intermediate 1A (2.2 g, 16.06 mmol, 48.8% yield) as an off-white solid. MS (ES): m/z=138.0 [M+H]+. 1H NMR (400 MHz, MeOD) δ ppm 8.45 (1 H, s), 8.33 (1 H, d, J=5.77 Hz), 7.50 (1 H, d, J=5.27 Hz), 2.62 (3 H, s).

Provenance & Evidence