Tetrahydrofuran → 2,4-Dichloro-6-fluorobenzoic acid

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Reaction Steps

A solution of 2.5 M n-butyllithium in hexane (8.72 mL, 21.8 mmol) was added to anhydrous THF (100 mL) at −78° C. under nitrogen with stirring, followed by the addition of 1.0 M potassium t-butyloxide in THF (21.81 mL, 21.8 mmol). The reaction mixture was stirred at −78° C. for 30 min, then 3,5-dichlorofluorobenzene (3.0 g, 18.2 mmol) was added over 10 min and the mixture was stirred at −78° C. for 40 minutes. Carbon dioxide gas was then bubbled into the reaction mixture for 10 min The reaction mixture was allowed to come to RT, diluted with ether (100 mL), extracted with a solution of aqueous 1.0 M sodium hydroxide (2×50 mL). The combined sodium hydroxide extract was washed with ether (100 mL). The sodium hydroxide layer was then acidified to pH 3 with a solution of aqueous concentrated HCl, extracted with ethyl acetate (2×50 mL). The combined ethyl acetate layers were dried over sodium sulfate and concentrated. The crude product was purified by ISCO flash chromatography (silica gel/hexane-ethyl acetate 100:0 to 0:100 gradient) to afford the title compound as a brown solid (1.34 g, 35% yield).

Provenance & Evidence