Methanol → (3,5-Dimethyl-4-hydroxy-phenyl)-acetic acid methyl ester

HRID 2199097Notes

Reaction equation

HRID 2199097 reaction equation
[CH3:1][C:2]1[CH:3]=[C:4]([CH2:10][C:11]([OH:13])=[O:12])[CH:5]=[C:6]([CH3:9])[C:7]=1[OH:8].S(=O)(=O)(O)O.[CH3:19]O>>[CH3:19][O:12][C:11](=[O:13])[CH2:10][C:4]1[CH:5]=[C:6]([CH3:9])[C:7]([OH:8])=[C:2]([CH3:1])[CH:3]=1

Participants

4

Reactant 3

HCID 887MethanolHCID 1118Sulfuric AcidHCID 16767514(4-Hydroxy-3,5-dimethylphenyl)acetic acid

Product 1

HCID 20582798(3,5-Dimethyl-4-hydroxy-phenyl)-acetic acid methyl esterYield 86%

Conditions

Temperature
70 °C

Procedure

A solution of (3,5-dimethyl-4-hydroxy-phenyl)-acetic acid (5a) (12.4 g, 0.069 mmol) in methanol (300 mL) was treated with concentrated sulfuric acid (6.25 mL). The resulting solution was heated to 70° C. overnight. At this time, the reaction was cooled to room temperature. The reaction was concentrated under vacuum. The residue was diluted with ethyl acetate (700 mL) and was washed with water (2×250 mL). The organics were dried over magnesium sulfate, filtered and concentrated under vacuum to give an orange solid. The solid was slurried in 10% ethyl acetate/petroleum ether and was stirred for 1 h. The solid was collected by filtration, washed with 10% ethyl acetate/petroleum ether, and dried under vacuum overnight. The residue was purified by column chromatography using silica gel eluted with 10-15% ethyl acetate in petroleum ether to afford (3,5-dimethyl-4-hydroxy-phenyl)-acetic acid methyl ester (6a) (1.93 g, 86%) as an off-white solid; EI(+)-HRMS m/z calcd for C11H14O3 (M+) 194.0943, found 191.0942. Molecular Weight=194.2324; Exact Mass=194.0943

Workup

  1. temperatureAt this time, the reaction was cooled to room temperature
  2. concentrationThe reaction was concentrated under vacuum
  3. additionThe residue was diluted with ethyl acetate (700 mL)
  4. washwas washed with water (2×250 mL)
  5. dry with materialThe organics were dried over magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated under vacuum
  8. customto give an orange solid
  9. filtrationThe solid was collected by filtration
  10. washwashed with 10% ethyl acetate/petroleum ether
  11. customdried under vacuum overnight
  12. customThe residue was purified by column chromatography
  13. washeluted with 10-15% ethyl acetate in petroleum ether

Sources & evidence

ORD record
ord-b995ee36594744a5864ab92136b5d12d
Source dataset
uspto-grants-2016_06
Patent number
USRE046024E1

Reaction notes

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