Methyl iodide → 1-Bromo-5-fluoro-4-methoxy-2-methylbenzene

HRID 1851634Notes

Reaction equation

HRID 1851634 reaction equation
[Br:1][C:2]1[C:7]([CH3:8])=[CH:6][C:5]([OH:9])=[C:4]([F:10])[CH:3]=1.[C:11](=O)([O-])[O-].[Cs+].[Cs+].IC>CN(C=O)C.C(OCC)(=O)C>[Br:1][C:2]1[CH:3]=[C:4]([F:10])[C:5]([O:9][CH3:11])=[CH:6][C:7]=1[CH3:8]

Participants

6

Reactant 3

HCID 6328Methyl iodideHCID 10796Cesium carbonateHCID 108997434-Bromo-2-fluoro-5-methylphenol

Product 1

HCID 227282131-Bromo-5-fluoro-4-methoxy-2-methylbenzeneYield 91.3%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

4-Bromo-2-fluoro-5-methylphenol (40 g, 0.19 mol), cesium carbonate (75 g, 0.23 mol), and iodomethane (15 ml, 0.23 mol) were combined in 100 ml of DMF and stirred at RT for one hour (exothermic). The solution was diluted with ethyl acetate and filtered. The solution was washed with water twice, dried with anhydrous sodium sulfate, filtered, and concentrated. The product was purified via silica gel column chromatography (RediSep 330 g column) using 0-50% ethyl acetate in hexane to afford 1-bromo-5-fluoro-4-methoxy-2-methylbenzene (38 g, 89% yield) as a colorless liquid. No [M+H] peak by LCMS. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 2.24 (s, 3 H) 3.76 (s, 3 H) 6.73 (d, J=8.80 Hz, 1 H) 7.13 (d, J=10.56 Hz, 1 H)

Workup

  1. filtrationfiltered
  2. washThe solution was washed with water twice
  3. dry with materialdried with anhydrous sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe product was purified via silica gel column chromatography (RediSep 330 g column)

Sources & evidence

ORD record
ord-0efaa89499574fd28dbb3d529f32cee5
Source dataset
uspto-grants-2015_02
Patent number
US08957083B2

Reaction notes

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