Methyl iodide → 1-Bromo-3-tert-butyl-5-(1,1-dimethoxyethyl)-2-methoxybenzene

HRID 2223763Notes

Reaction equation

HRID 2223763 reaction equation
[CH:1]([O:6][CH3:7])([O:4][CH3:5])OC.[Br:8][C:9]1[C:10](O)=[C:11]([C:18]([CH3:21])([CH3:20])[CH3:19])[CH:12]=[C:13](C(=O)C)[CH:14]=1.[CH3:23]I.[C:25](=[O:28])([O-])[O-].[K+].[K+]>C12(CS(O)(=O)=O)C(C)(C)C(CC1)CC2=O.CCCCCCC.O.CN(C)C=O.CO>[Br:8][C:9]1[CH:14]=[C:13]([C:1]([O:4][CH3:5])([O:6][CH3:7])[CH3:23])[CH:12]=[C:11]([C:18]([CH3:19])([CH3:21])[CH3:20])[C:10]=1[O:28][CH3:25]

Participants

10

Reactant 4

HCID 6328Methyl iodideHCID 9005Trimethyl orthoformateHCID 11430Potassium CarbonateHCID 230937111-(3-Bromo-5-tert-butyl-4-hydroxyphenyl)ethanone

Product 1

HCID 230937191-Bromo-3-tert-butyl-5-(1,1-dimethoxyethyl)-2-methoxybenzeneYield 98%

Reagents, catalysts & solvents 5

HCID 18462Bicyclo[2.2.1]heptane-1-methanesulfonic acid, 7,7-dimethyl-2-oxo-, (1S)-CatalystHCID 887MethanolSolventHCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8900HeptaneSolvent

Procedure

Under nitrogen atmosphere, methanol (678 mL), trimethyl orthoformate (796 g, 7.50 mol), and (±)-10-camphorsulfonic acid [(±)-CSA] (11.6 g, 0.050 mol, 2 mol %) were added to 1-(5-bromo-3-tert-butyl-4-hydroxyphenyl)ethanone (678 g, 2.50 mol), followed by stirring. After stirring for 2.7 hours, N,N-dimethylformamide (1.7 L) was added and this was cooled on ice. Furthermore, methyl iodide (700 g) was added followed by potassium carbonate (518 g), and this was stirred at room temperature. After stirring for 5.5 hours, water (4750 mL) and n-heptane (4750 mL) were added and the solution was separated. The organic layer was washed with water (2370 mL), and then sodium sulfate (120.2 g) was added. After stirring, the mixture was filtered by suction, and rinsed with n-heptane (250 mL). The filtrate was evaporated (50° C.) to obtain 808 g of the subject compound as a brown oily substance (yield: 98%, HPLC purity: 96.8%).

Workup

  1. stirringAfter stirring for 2.7 hours
  2. temperaturethis was cooled on ice
  3. stirringthis was stirred at room temperature
  4. stirringAfter stirring for 5.5 hours
  5. customthe solution was separated
  6. washThe organic layer was washed with water (2370 mL)
  7. additionsodium sulfate (120.2 g) was added
  8. stirringAfter stirring
  9. filtrationthe mixture was filtered by suction
  10. washrinsed with n-heptane (250 mL)
  11. customThe filtrate was evaporated (50° C.)

Sources & evidence

ORD record
ord-fdf1e8239bb24f6f90a3ae60bf0f9942
Source dataset
uspto-grants-2008_05
Patent number
US07375236B2

Reaction notes

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