Triethylamine → 6-Fluoro-4-hydroxy-3-methyl-naphthalene-2-carboxylic acid methyl ester

Participants

Reaction Steps

To a solution of 2-(4-fluoro-benzylidene)-3-methyl-succinic acid 1-methyl ester (1 g, 4 mmol) in anhydrous tetrahydrofuran (10 mL), trifluoroacetic anhydride (3.3 g, 15.7 mmol) was added in one portion followed by the addition of triethylamine (3.3 ml, 24 mmol) dropwise. After being stirred at room temperature for 4 hours, the mixture was acidified to pH 3 with 5% aqueous hydrochloric acid and extracted with ethyl acetate (20 mL). The organic layer was concentrated in vacuo. The residue was dissolved in methanol (15 mL). The resulting solution was cooled to 0° C., then treated with sodium borohydride (380 mg, 10 mmol), and stirred for 1 hour. The reaction mixture was diluted with ethyl acetate (20 mL) and 5% aqueous hydrochloric acid (20 mL). The aqueous phase was separated and extracted with ethyl acetate (15 mL×3). The combined organic layers were washed with brine (40 mL), dried over sodium sulfate, filtered, and concentrated in vacuo. The residue was purified by column chromatography (elution with 10% ethyl acetate in hexanes) to afford 6-fluoro-4-hydroxy-3-methyl-naphthalene-2-carboxylic acid methyl ester (740 mg, 80%) as a pale solid.

Provenance & Evidence