Sodium Carbonate → (E)-2-Bromo-4-(2,5-difluorostyryl)-5-fluoropyridine

Participants

Reaction Conditions

Reaction Steps

A suspension of 2-bromo-5-fluoropyridin-4-ylboronic acid (1.569 g, 7.14 mmol) and 1,4-difluoro-2-vinylbenzene (1 g, 7.14 mmol) in dimethylformamide (20 mL) was flushed with a balloon of oxygen. To this was added sodium carbonate (1.51 g, 14.3 mmol) and palladium(II) acetate (0.16 g, 0.71 mmol) as solids in one portion. The flask was flushed with another balloon of oxygen and fitted with a balloon of oxygen. The reaction was warmed to 50° C. After 1 h, the reaction was treated with a second portion of sodium carbonate (0.75 g) and boronic acid (1.6 g). This process was repeated twice more (total boronic acid addition=6.3 g). The reaction was cooled to room temperature, diluted with ether, washed with water (3×), then brine, dried over magnesium sulfate, and concentrated. Column chromatography (2.5%→5% EtOAc/Hex) gave 89 mg (4.0%) as a white solid. 1H NMR (CDCl3) Shift: 8.28 (d, J=1.8 Hz, 1H), 7.68 (d, J=5.5 Hz, 1H), 7.49 (d, J=16.5 Hz, 1H), 7.33 (ddd, J=8.9, 5.8, 3.1 Hz, 1H), 7.17 (d, J=16.8 Hz, 1H), 6.98-7.14 (m, 2H). 19F NMR (CDCl3) Shift: −118.54 (d, J=13.0 Hz, 1F), −122.71 (br. s., 1F), −135.71 (br. s., 1F). Mass spec.: 314.0 (MH)+.

Provenance & Evidence