2-Amino-3-(trifluoromethyl)pyridine-5-boronic acid pinacol ester

79456-34-1

73183-34-3

947249-01-6

GENERAL STEPS: 5-bromo-3-(trifluoromethyl)pyridin-2-amine (180 g) was mixed with 1,4-dioxane (3600 mL) in a flask and stirred. Bis(pinacolato)diboron (284.47 g), potassium acetate (109.95 g) and 1,1'-bis(diphenylphosphino)ferrocene palladium(II) dichloride dichloromethane complex (18 g) were added sequentially at 25-30 °C. The reaction mixture was heated to 95-100 °C and maintained for 15-16 hours. After completion of the reaction, it was cooled to 25-30 °C, filtered through a bed of diatomaceous earth and the filter bed was washed with ethyl acetate (1800 mL). The filtrate was concentrated under reduced pressure to give the crude product 2-amino-3-(trifluoromethyl)pyridine-5-boronic acid pinacol ester (450 g). Purification step: the crude product was dissolved in methanol (1800 mL), activated carbon (45 g) and silica gel (60-120 mesh, 450 g) were added, and stirred at 25-30 °C for 1 hour. The mixture was filtered through a bed of diatomaceous earth and washed with methanol (450 mL). The filtrate was slowly added to cold water (6750 mL) over a period of 1 hour, maintaining the temperature at 0-5 °C. The precipitate was collected by filtration and washed with cold water (900 mL). The wet solid was dried at 45-50 °C to give purified 2-amino-3-(trifluoromethyl)pyridine-5-boronic acid pinacol ester (209 g). Yield: 97.47%. Purity: 98.43%. 1H NMR (300 MHz, DMSO-d6): δ 8.38 (s, 1H), 7.80 (s, 1H), 6.92 (s, 2H), 1.27 (s, 12H). MS: m/z 289.1 (M + 1)