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

HRID 244335Notes

Reaction equation

HRID 244335 reaction equation
[Br:1][C:2]1[C:3](O)=[C:4]([C:11]([CH3:14])([CH3:13])[CH3:12])[CH:5]=[C:6](C(=O)C)[CH:7]=1.[CH:16]([O:21][CH3:22])([O:19][CH3:20])OC.[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:1][C:2]1[CH:7]=[C:6]([C:16]([O:19][CH3:20])([O:21][CH3:22])[CH3:23])[CH:5]=[C:4]([C:11]([CH3:12])([CH3:14])[CH3:13])[C:3]=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

To 1-(5-bromo-3-tert-butyl-4-hydroxyphenyl)ethanone (678 g, 2.50 mol), 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 and stirred under a nitrogen atmosphere. Alter stirring for 2.7 hours, N,N-dimethylformamide (1.7 L) were added thereto. The resultant mixture was cooled on ice. Subsequently, methyl iodide (700 g) and potassium carbonate (518 g) were added in this order and stirred at room temperature. After stirring for 5.5 hours, water (4750 mL) and n-heptane (4750 mL) were added to the reaction solution to separate liquid layers. The organic layer was washed with water (2370 mL), and sodium sulfate (120.2 g) was added thereto and stirred. Then, this layer was vacuum filtered. At this time, washing with n-heptane (250 mL) was carried out. The solvent in the filtrate was evaporated (50° C.) to give 808 g of the captioned compound as a brown oily material (yield: 98%; HPLC purity: 96.8%).

Workup

  1. stirringAlter stirring for 2.7 hours
  2. stirringstirred at room temperature
  3. stirringAfter stirring for 5.5 hours
  4. customto separate liquid layers
  5. washThe organic layer was washed with water (2370 mL), and sodium sulfate (120.2 g)
  6. additionwas added
  7. stirringstirred
  8. filtrationfiltered
  9. washAt this time, washing with n-heptane (250 mL)
  10. customThe solvent in the filtrate was evaporated (50° C.)

Sources & evidence

ORD record
ord-943d3f62442b49b7b6802558530baeb1
Source dataset
uspto-grants-2014_02
Patent number
US08658620B2

Reaction notes

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