2,2'-Bipyridine → HCID 86694126, compound

Participants

Reaction Conditions

Reaction Steps

Tert-butyl (2-chloro-5-fluoropyridin-3-yl)carbamate (Intermediate 36) (0.500 g, 2.027 mmol) was dissolved in dichloromethane (5 mL) and treated with trifluoroacetic acid (0.5 mL). The mixture was stirred at 45° C. for 1 hour then cooled to room temperature. The solution was evaporated to dryness under reduced pressure and the crude amine partitioned between 50% saturated sodium bicarbonate (80 mL) and ethyl acetate (60 mL). The organic was dried with magnesium sulfate and evaporated to dryness under reduced pressure. The solid amine intermediate was combined with anhydrous cupric acetate (0.375 g, 2.065 mmol), sodium carbonate (1.00 g, 9.43 mmol), 2,2′-bipyridyl (0.325 g, 2.081 mmol) and cyclopropylboronic acid (0.305 g, 3.55 mmol). 1,2-Dichloroethane (5 mL) was added and the mixture heated at 70° C. in air. After 2 hours, the mixture was cooled and diluted with ethyl acetate (300 mL). It was washed with a mixture of saturated ammonium chloride (50 mL), water (100 mL), and ammonium hydroxide (20 mL) before drying with magnesium sulfate and evaporating to dryness under reduced pressure. Purification using silica chromatography (hexane to ethyl acetate gradient) gave 2-chloro-N-cyclopropyl-5-fluoropyridin-3-amine (0.270 g, 1.447 mmol, 71.4% yield).

Provenance & Evidence