Methyl iodide → Methyl 3-hydroxy-5-methoxybenzoate

HRID 881984Notes

Reaction equation

HRID 881984 reaction equation
[OH:1][C:2]1[CH:3]=[C:4]([CH:9]=[C:10]([OH:12])[CH:11]=1)[C:5]([O:7][CH3:8])=[O:6].[C:13](=O)([O-])[O-].[K+].[K+].IC>CC(C)=O>[OH:1][C:2]1[CH:3]=[C:4]([CH:9]=[C:10]([O:12][CH3:13])[CH:11]=1)[C:5]([O:7][CH3:8])=[O:6]

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 11430Potassium CarbonateHCID 75076Methyl 3,5-Dihydroxybenzoate

Product 1

HCID 13941268Methyl 3-hydroxy-5-methoxybenzoateYield 38.5%

Reagents, catalysts & solvents 1

HCID 180AcetoneSolvent

Conditions

Temperature
60 °C

Procedure

A suspension of methyl 3,5-dihydroxybenzoate (89 mmol, 15 g), potassium carbonate (107 mmol, 14.79 g) and iodomethane (89 mmol, 5.55 ml, 12.66 g) in acetone (300 ml) was stirred at 60° C. for 4 hours. TLC showed a mixture of 3 compounds which were starting material, mono methylated product and demethylated product. After cooling to room temperature, acetone was removed under reduced pressure and the oily residue was partitioned between ethyl acetate and water. The organic layer was washed with brine, dried over Na2SO4, filtered and evaporated under reduced pressure. The crude product was purified using normal phase chromatography was purified using normal phase chromatography eluting with ethyl acetate and increasing amounts of heptane to give methyl 3-hydroxy-5-methoxybenzoate (6.25 g) as a clear oil.

Workup

  1. additiona mixture of 3 compounds which
  2. temperatureAfter cooling to room temperature
  3. customacetone was removed under reduced pressure
  4. customthe oily residue was partitioned between ethyl acetate and water
  5. washThe organic layer was washed with brine
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. customevaporated under reduced pressure
  9. customThe crude product was purified
  10. customwas purified
  11. washeluting with ethyl acetate
  12. temperatureincreasing amounts of heptane

Sources & evidence

ORD record
ord-867151cae3c340838d1664a7ba89c23c
Source dataset
uspto-grants-2015_03
Patent number
US08993757B2

Reaction notes

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