反应详情

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).

1. temperatureThe reaction mixture was heated
2. temperatureat reflux for 3 hours
3. customThe acetone was removed in vacuo
4. additionThe residue was diluted with water
5. extractionthe resulting mixture was extracted three times with ethyl acetate
6. washThe combined organic phases were washed with brine
7. dry with materialdried over MgSO4
8. filtrationfiltered
9. concentrationconcentrated