Hydrochloric Acid → Methyl 4-acetyl-2-methoxybenzoate

HRID 410486Notes

Reaction equation

HRID 410486 reaction equation
Br[C:2]1[CH:11]=[CH:10][C:5]([C:6]([O:8][CH3:9])=[O:7])=[C:4]([O:12][CH3:13])[CH:3]=1.[CH2:14]([O:18]C=C)[CH2:15]CC.C(=O)([O-])[O-].[K+].[K+].Cl>C(OCC)(=O)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.O.CN(C=O)C>[C:14]([C:2]1[CH:11]=[CH:10][C:5]([C:6]([O:8][CH3:9])=[O:7])=[C:4]([O:12][CH3:13])[CH:3]=1)(=[O:18])[CH3:15]

Participants

9

Reactant 4

HCID 313Hydrochloric AcidHCID 8108Butyl vinyl ether2×HCID 11430Potassium CarbonateHCID 15128242Methyl 4-bromo-2-methoxybenzoate

Product 1

HCID 13124242Methyl 4-acetyl-2-methoxybenzoateYield 25.6%

Reagents, catalysts & solvents 4

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
122 °C

Procedure

A flask was charged with methyl 4-bromo-2-methoxybenzoate (250 mg, 1.020 mmol), vinyl butyl ether (131 μl, 1.020 mmol), potassium carbonate (169 mg, 1.224 mmol), 1,3-(bis(diphenylohpsophine)propane (25.2 mg, 0.061 mmol) and palladium (II) acetate (6.87 mg, 0.031 mmol). The flask was sealed and 3 evacuation/argon purges were performed. DMF (4554 μl) and Water (546 μl) were added and the reaction was heated in a microwave at 122° C. for 75 minutes. Additional vinyl butyl ether (131 μl, 1.020 mmol) was added and the reaction was heated an additional 30 minutes in a MW at 122° C. Once complete the reaction was stirred overnight at 100° C. with conventional heating. The reaction was then cooled. HCl (5%, 8 mL) was added and the mixture was stirred for 30 minutes and then diluted with ethyl acetate and transferred to a separatory funnel. The organic layer was washed with aqueous saturated NaHCO3, brine, dried over Na2SO4, filtered and concentrated. Flash chromatography (0-50% EtOAc/hexanes) afforded methyl 4-acetyl-2-methoxybenzoate (54.4 mg, 0.261 mmol, 25.6% yield). MS ESI: [M+H]+ m/z 200.1. 1H NMR (600 MHz, DMSO-d6) δ 7.70 (d, J=7.9, 1H), 7.57 (dd, J=1.1, 7.9, 1H), 7.53 (s, 1H), 3.86 (s, 3H), 3.78 (s, 3H), 2.49-2.44 (m, 3H).

Workup

  1. customThe flask was sealed
  2. temperaturethe reaction was heated an additional 30 minutes in a MW at 122° C
  3. temperatureThe reaction was then cooled
  4. stirringthe mixture was stirred for 30 minutes
  5. customtransferred to a separatory funnel
  6. washThe organic layer was washed with aqueous saturated NaHCO3, brine
  7. dry with materialdried over Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated

Sources & evidence

ORD record
ord-e4f760d3af2a43adb537d31bc17d3ebd
Source dataset
uspto-grants-2014_06
Patent number
US08759366B2

Reaction notes

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