Cesium carbonate → 5-[4-Difluoromethoxy-3-methoxy-2-(3-methoxymethyl-oxetan-3-ylmethoxy)-phenyl]-2,3-dihydro-isoindol-1-one

Participants

Reaction Conditions

Reaction Steps

To a stirring solution of 3-((6-bromo-3-(difluoromethoxy)-2-methoxyphenoxy)methyl)-3-(methoxymethyl)oxetane (200 mg, 0.521 mmol) in dimethylformamide (10 mL) was purged with argon for 1 h. To this cesium carbonate (507 mg, 1.563 mmol), tetrakis(triphenylphosphine) palladium(0) (30 mg, 0.026 mmol) and 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)isoindolin-1-one (162 mg, 0.626 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 (50 mg, 22%).

Provenance & Evidence