7-bromo-3-fluoro-2-methoxy-9H-xanthen-9-one → 7-bromo-3-fluoro-2-methoxy-9-methyl-9H-xanthen-9-ol

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To a suspension of 7-bromo-3-fluoro-2-methoxy-9H-xanthen-9-one (25 g, 73.4 mmol) in THF (500 mL) was added MeMgCl (2.0 equiv. 146.75 mmol, 48.9 mL, 3.0 M solution in THF) at −20° C. (internal temp) slowly over 30 minutes. The resulting mixture was allowed to reach ambient temperature where it was maintained for 12 hours. The reaction was quenched by adding saturated NH4Cl. The phases were separated and the aqueous layer was extracted with EtOAc (2×300 mL). The combined organic extracts were washed with brine, dried over Na2SO4, filtered and concentrated to afford 25 g of 7-bromo-3-fluoro-2-methoxy-9-methyl-9H-xanthen-9-ol that was used in the next step without further purification. A solution of the derived alcohol (25 g) was dissolved in DCM (300 mL) and pPTS (250 mg, 0.995 mmol) was added. The mixture was heated to reflux for 2 hours at which time the reaction was cooled to rt and washed with NaHCO3 (100 mL). The layers were separated and the organic layer was washed with brine, dried over Na2SO4, filtered and concentrated. The resulting residue was purified via chromatography (hexanes/DCM, 3:1) to provide 7-bromo-3-fluoro-2-methoxy-9-methylene-9H-xanthene as an orange solid.

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