Methanol → Methyl 4-hydroxy-3-methoxyphenylacetate

HRID 1063815Notes

Reaction equation

HRID 1063815 reaction equation
S(=O)(=O)(O)O.[OH:6][C:7]1[CH:12]=[CH:11][C:10]([CH2:13][C:14]([OH:16])=[O:15])=[CH:9][C:8]=1[O:17][CH3:18].[CH3:19]O>>[CH3:19][O:15][C:14](=[O:16])[CH2:13][C:10]1[CH:11]=[CH:12][C:7]([OH:6])=[C:8]([O:17][CH3:18])[CH:9]=1

Participants

4

Reactant 3

HCID 887MethanolHCID 1118Sulfuric AcidHCID 1738Homovanillic Acid

Product 1

HCID 85214Methyl 4-hydroxy-3-methoxyphenylacetate

Conditions

Temperature
90 °C

Procedure

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.

Workup

  1. temperatureThe reaction was then cooled to room temperature
  2. customthe solvent was removed under reduced pressure
  3. extractionextracted with diethylether (2×300 ml)
  4. washThe combined organic extracts were washed with saturated sodium bicarbonate solution (2×100 ml), brine (100 ml)
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated under reduced pressure
  7. customThe 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

Sources & evidence

ORD record
ord-417a67c5e5784f0d953e751a3f807346
Source dataset
uspto-grants-2005_11
Patent number
US06967204B2

Reaction notes

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