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

HRID 529414Notes

Reaction equation

HRID 529414 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-fcffb780bad24fd6b9522ba514240085
Source dataset
uspto-grants-2016_05
Patent number
US09346827B2

Reaction notes

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