Sodium Carbonate → Ethyl {4-[4-[(difluoromethyl)oxy]-9-(ethyloxy)-1-oxo-1,3-dihydro-2H-benzo[f]isoindol-2-yl]-3-fluorophenyl}acetate

Participants

Reaction Conditions

Reaction Steps

To a solution of ethyl {4-[9-(ethyloxy)-4-hydroxy-1-oxo-1,3-dihydro-2H-benzo[f]isoindol-2-yl]-3-fluorophenyl}acetate (2.40 g, 5.67 mmols) in DMF (30 ml) was added sodium chlorodifluoroacetate (1.72 g, 11.34 mmol) and sodium carbonate (1.20 g, 11.34 mmol). The mixture was heated to 100° C. for 3 hours. Further sodium chlorodifluoroacetate (1.72 g, 11.34 mmol) was added, heating continued for 1.5 hours, and the same amount added again and heating continued for 30 minutes. The mixture was cooled to room temperature and partitioned between ethyl acetate ×2 and water. The combined organics were washed with water ×3 and brine. This was dried over magnesium sulphate, filtered and evaporated to a brown oil. This was purified by chromatography on silica gel, eluting with ethyl acetate (5-40%) in hexane to give the title compound as a yellow solid (0.60 g, 1.27 mmol).

Provenance & Evidence