Benzyl Bromide → 4-Benzyloxy-6-fluoro-3-methyl-naphthalene-2-carboxylic acid methyl ester

Participants

Reaction Steps

Benzyl bromide (10 mL, 82.51 mmol) was added to a mixture of 6-fluoro-4-hydroxy-3-methyl-naphthalene-2-carboxylic acid methyl ester (15.56 g, 66.43 mmol) and potassium carbonate (19.26 g, 136.6 mmol) in acetone (300 mL). The reaction mixture was heated at reflux for 3 hours. The acetone was removed in vacuo. The residue was diluted with water, and the resulting mixture was extracted three times with ethyl acetate. The combined organic phases were washed with brine, dried over MgSO4, filtered, and concentrated. A concentrated solution of the crude product in 25% ethyl acetate in hexanes was loaded onto a Analogix SuperFlash™ column. Flash chromatography (25-50% ethyl acetate in hexanes) provided 14.27 g (66% yield) of 4-benzyloxy-6-fluoro-3-methyl-naphthalene-2-carboxylic acid methyl ester as a slightly yellow solid. 1H NMR (300 MHz, DMSO-d6) δ ppm 8.34 (s, 1 H), 8.19 (dd, J=8.9, 5.9 Hz, 1 H), 7.64 (dd, J=10.7, 2.3 Hz, 1 H), 7.57 (d, J=6.6 Hz, 2 H), 7.36-7.54 (m, 4 H), 4.98 (s, 2 H), 3.89 (s, 3 H), 2.56 (s, 3 H).

Provenance & Evidence