Sulfuric Acid → HCID 67382994, compound

Participants

Reaction Conditions

Reaction Steps

To a 1 L flask charged with 2-(4-bromo-3-fluorophenoxy)-5-methoxybenzoic acid (100 g, 293 mmol) was added sulfuric acid (391 mL, 7329 mmol). The resulting slurry was heated to 80° C. for 2 hours. The reaction was removed from the oil bath, cooled to rt and poured into a 3 L flask containing 2 L of ice water. The derived slurry was vigorously stirred for 2 hours before being filtered. The derived solid was washed well with water (3×500 mL), 3 N NaOH (2×500 mL) and water (2×500 mL). The wet solid was then washed with ether (2×250 mL) and dried under a vacuum at 50° C. overnight. The solid was then azeotropped from toluene (3×100 mL) to provide 41 g of a 4:1 mixture of 2-bromo-1-fluoro-7-methoxy-9H-xanthen-9-one:2-bromo-3-fluoro-7-methoxy-9H-xanthen-9-one (40.0 g, 123.9 mmol, 42.2% yield). A portion of this material (10 g) was slurried in hot IPA (200 mL) and placed in the refrigerator overnight. The derived solid was filtered and purified by silica gel chromatography (100% CH2Cl2) to provide 2-bromo-1-fluoro-7-methoxy-9H-xanthen-9-one (4.1 g) and 2-bromo-3-fluoro-7-methoxy-9H-xanthen-9-one (0.95 g) both as light white solids.

Provenance & Evidence