Sodium Carbonate → Ethyl 3-(2,4-difluorophenyl)-1-(4-methoxybenzyl)-1H-thieno[2,3-c]pyrazole-5-carboxylate

Participants

Reaction Conditions

Reaction Steps

Ethyl 3-bromo-1-(4-methoxybenzyl)-1H-thieno[2,3-c]pyrazole-5-carboxylate (1.1422 g, 2.89 mmol), 2,4-difluorophenylboronic acid (1.867 g, 11.82 mmol), sodium carbonate (1.614 g, 15.23 mmol), and [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (0.426 g, 0.582 mmol) were dissolved in dioxane (14.45 ml) at 25° C. under Ar in a sealed heavy-walled reaction vessel. The reaction mixture was heated to 80° C. and allowed to stir for 2 h. Cesium carbonate (1.52 g, 4.67 mmol) was added. The reaction was allowed to stir for 2 h. The reaction was stopped, cooled to room temperature, quenched by addition of saturated aqueous ammonium chloride (20 mL), and the mixture extracted with ethyl acetate (3×20 mL). The combined organic phases were washed with saturated aqueous sodium chloride (1×15 mL), dried (sodium sulfate), filtered, and the solvent evaporated under reduced pressure. The crude product was purified by flash chromatography (RediSep SiO2, 120 g column) on a CombiFlash purification system eluting with ethyl acetate-hexanes (0-15%). The title compound (1.0147 g, 2.368 mmol, 82% yield) was recovered as a white solid. LC-MS [M+1]=429.3

Provenance & Evidence