Methyl iodide → 1-Bromo-4-chloro-2-fluoro-3-methoxybenzene

HRID 2249361Notes

Reaction equation

HRID 2249361 reaction equation
[Br:1][C:2]1[C:3]([F:10])=[C:4]([OH:9])[C:5]([Cl:8])=[CH:6][CH:7]=1.CI.[C:13](=O)([O-])[O-].[K+].[K+]>C(#N)C.O>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([Cl:8])=[C:4]([O:9][CH3:13])[C:3]=1[F:10]

Participants

6

Reactant 3

HCID 6328Methyl iodideHCID 11430Potassium CarbonateHCID 666010023-Bromo-6-chloro-2-fluorophenol

Product 1

HCID 666003671-Bromo-4-chloro-2-fluoro-3-methoxybenzeneYield 96.9%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6342AcetonitrileSolvent

Procedure

A heterogeneous mixture of 3-bromo-6-chloro-2-fluorophenol (14.4 g, 0.064 mol), methyl iodide (13.5 g, 0.096 mol) and potassium carbonate (8.8 g, 0.064 mol) in acetonitrile (100 mL) was heated under reflux for 2 hours. The mixture was cooled, diluted with water (100 mL) and extracted with ethyl ether (2×150 mL). The combined extracts were dried and concentrated. The dark oil was purified by chromatography (5% ethyl acetate in hexanes) to give 1-bromo-4-chloro-2-fluoro-3-methoxybenzene (14.8 g, 0.062 mol): 1H NMR (CDCl3): δ 7.20 (m, 1H), 7.10 (dd, 1H), 4.0 (s, 3H).

Workup

  1. temperaturewas heated
  2. temperatureunder reflux for 2 hours
  3. temperatureThe mixture was cooled
  4. extractionextracted with ethyl ether (2×150 mL)
  5. customThe combined extracts were dried
  6. concentrationconcentrated
  7. customThe dark oil was purified by chromatography (5% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-c0b47a637c3d4e7883b36936b0f709e4
Source dataset
uspto-grants-2008_01
Patent number
US07314849B2

Reaction notes

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