Methanol → Methyl 4-hydroxy-3-methoxyphenylacetate

Participants

Reaction Conditions

Reaction Steps

Concentrated sulfuric acid (12 ml) was added to a solution of (4-hydroxy-3-methyoxy-phenyl)-acetic acid (22.5 g, 123 mmol) in methanol (450 ml) at room temperature, and the reaction was heated to 90° C. for 2.45 hours. The reaction was then cooled to room temperature and stirred for 18 hours, and the solvent was removed under reduced pressure. The residue was suspended in ice water (300 ml) and extracted with diethylether (2×300 ml). The combined organic extracts were washed with saturated sodium bicarbonate solution (2×100 ml), brine (100 ml), dried over Na2SO4 and concentrated under reduced pressure. The residue was purified by flash column chromatography on silica gel eluting with a solvent gradient of cyclohexane:ethyl acetate (80:20 changing to 70:30, 60:40 and finally 1:1, by volume) to give (4-hydroxy-3-methoxy-phenyl)-acetic acid methyl ester (23 g) as a yellow oil. 1H NMR (400 MHz, CDCl3): δ=6.82-6.85 (1H, d), 6.80 (1H, s), 6.76-6.79 (1H, d), 5.49 (1H 3.66 (3H, s), 3.53 (2H, s) ppm. LRMS (electrospray): m/z [M+Na]+ 219.

Provenance & Evidence