Ethyl Acetate → (4-Benzyloxy-6-fluoro-naphthalen-2-yl)-acetic acid methyl ester

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Reaction Steps

To a stirred solution of 1-benzyloxy-3-chloromethyl-7-fluoro-naphthalene (19.3 g, 64.2 mmol) in a 2:1 THF-MeOH (300 mL) was added K2CO3 (9.75 g, 70.6 mmol) and PdCl2 (PPh3)2 (2.25 g, 3.2 mmol) at room temperature. The solution was degassed (by purging with argon for 5 minutes) and stirred under carbon monoxide (balloon pressure) at room temperature overnight. The solvents were distilled off under reduced pressure, and the obtained crude residue was diluted with water (150 ml) and extracted with ethyl acetate (2×200 mL). The combined organic extracts were washed with water (50 ml), brine (50 ml), dried over anhydrous sodium sulfate and concentrated in vacuo to obtain the crude product. Silica gel chromatography (100-200 mesh, 5% ethyl acetate in hexane) yielded (4-benzyloxy-6-fluoro-naphthalen-2-yl)-acetic acid methyl ester (18.5 g, 89%) as a white solid. MS cald. for C20H17FO3 [(M+H)+]: 325, obsd. 325.2.

Provenance & Evidence