Methyl iodide → Methyl 4-bromo-5-fluoro-2-nitrobenzoate

HRID 924376Notes

Reaction equation

HRID 924376 reaction equation
[Br:1][C:2]1[C:10]([F:11])=[CH:9][C:5]([C:6]([OH:8])=[O:7])=[C:4]([N+:12]([O-:14])=[O:13])[CH:3]=1.[C:15](=O)([O-])[O-].[K+].[K+].CI>CN(C=O)C>[Br:1][C:2]1[C:10]([F:11])=[CH:9][C:5]([C:6]([O:8][CH3:15])=[O:7])=[C:4]([N+:12]([O-:14])=[O:13])[CH:3]=1

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 11430Potassium CarbonateHCID 299192484-Bromo-5-fluoro-2-nitrobenzoic acid

Product 1

HCID 67473451Methyl 4-bromo-5-fluoro-2-nitrobenzoateYield 94.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

To a stirred solution of 4-bromo-5-fluoro-2-nitrobenzoic acid (Ark Pharm, 5.387 g, 20.40 mmol) in DMF (80.0 mL) at 0° C. was added potassium carbonate (5.870 g, 42.47 mmol), followed by methyl iodide (8.789 g, 61.92 mmol). After stirring at 0° C. for 15 min., the reaction was heated to 40° C. for 2 h. The mixture was filtered and concentrated. The residue was dissolved in EtOAc (150 mL), washed with water (2×100 mL), brine (100 mL), dried over Na2SO4, and concentrated under reduced pressure. The resulting residue was purified by flash chromatography on silica gel (0-50% EtOAc in hexanes) to give the sub-title compound as a pale yellow oil (5.348 g, 94%). LCMS calc. for C8H6BrFNO4 (M+H)+: m/z=277.9. found no ionization.

Workup

  1. temperaturethe reaction was heated to 40° C. for 2 h
  2. filtrationThe mixture was filtered
  3. concentrationconcentrated
  4. dissolutionThe residue was dissolved in EtOAc (150 mL)
  5. washwashed with water (2×100 mL), brine (100 mL)
  6. dry with materialdried over Na2SO4
  7. concentrationconcentrated under reduced pressure
  8. customThe resulting residue was purified by flash chromatography on silica gel (0-50% EtOAc in hexanes)

Sources & evidence

ORD record
ord-aa6cf5100eb64b44b5dbf16d7a018040
Source dataset
uspto-grants-2016_03
Patent number
US09278950B2

Reaction notes

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