Cesium carbonate → 5-(4-(Difluoromethoxy)-3-methoxy-2-propoxyphenyl)isoindolin-1-one

Participants

Reaction Conditions

Reaction Steps

To a stirring solution of 6-bromo-3-(difluoromethoxy)-2-methoxyphenol (300 mg, 1.115 mmol) in acetonitrile (10 mL) was added potassium carbonate (495 mg, 2.334 mmol) and propyl bromide (411 mg, 3.34 mmol) and the resultant reaction mixture was heated to 80° C. for 3 h. The reaction mixture was cooled to RT, filtered through celite and the filtrate was concentrated under reduced pressure to afford 300 mg of 1-Bromo-4-(difluoromethoxy)-3-methoxy-2-propoxybenzene (Int14-F2) as a solid. A stirring solution of 1-bromo-4-(difluoromethoxy)-3-methoxy-2-propoxybenzene (300 mg, 0.964 mmol) in dimethylformamide (5 mL) was purged with argon for 1 h, to this cesium carbonate (625 mg, 1.926 mmol), tetrakis(triphenylphosphine) palladium(0) (37 mg, 0.032 mmol) and 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)isoindolin-1-one (199 mg, 0.771 mmol) were added and the resultant reaction mixture was heated to 80-90° C. for 3 h. The reaction mixture was cooled to RT, filtered and the filtrate was diluted with water and extracted with ethyl acetate (3×). The combined ethyl acetate layer was washed with brine and dried over anhydrous sodium sulphate and concentrated under reduced pressure. Purification of the residue by column chromatography (silica gel, 0-20% ethyl acetate in pet ether) afforded the title compound as a solid (40 mg, 11%).

Provenance & Evidence