反应详情

温度

80 °C

To a solution of 2,2-Difluoro-1-{(4S,5R)-4-fluoromethyl-2,2-dimethyl-5-[4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-oxazolidin-3-yl}-ethanone (634 mg, 1.53 mmol) in a mixture of toluene (12 ml) and ethanol (9 ml) is added 2-(5-Bromo-pyridin-2-yl)-pyrrolidine-1-carboxylic acid tert-butyl ester (500 mg, 1.53 mmol), aqueous sodium bicarbonate solution (2M, 6 mmol, 3 ml), and 1,1′Bis(diphenylphosphino)ferrocene]dichloropalladium (II) (57 mg, 0.08 mmol). The stirred reaction mixture is heated at 80° C. under a blanket of nitrogen for 1 hour. The reaction is concentrated to ⅓ its volume and partitioned between ethyl acetate (25 ml) and water (25 ml). The organic phase is washed with saturated brine (25 ml) and concentrated on to silica gel (3 g). Purification by column chromatography (40 g silica gel, ethyl acetate/heptane 0-100%) affords the title compound (500 mg): 1H NMR (400 MHz, CDCl3) 1.25 (s, 5H) 1.48 (s, 4H), 1.64 (s, 3H), 1.70 (s, 3H), 1.85-1.98 (m, 2H), 1.99-2.1 (1H), 2.3-2.48 (m, 1H), 3.5-3.74 (m, 2H), 4.54-5.1 (m, 4H), 5.23-5.33 (m, 1H), 6.13 (t, 1H), 7.23-7.31 (m, 1H) 7.5-7.57 (m, 2H), 7.57-7.67 (m, 2H), 7.78-7.87 (m, 1H), 8.77 (s, 1H). m/z M+H 534.2.

1. customThe stirred reaction mixture
2. concentrationThe reaction is concentrated
3. custompartitioned between ethyl acetate (25 ml) and water (25 ml)
4. washThe organic phase is washed with saturated brine (25 ml)
5. concentrationconcentrated on to silica gel (3 g)
6. customPurification by column chromatography (40 g silica gel, ethyl acetate/heptane 0-100%)