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

HRID 1496876Notes

Reaction equation

HRID 1496876 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 two hours. The mixture was cooled, diluted with water (100 mL) and extracted with diethyl 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 two hours
  3. temperatureThe mixture was cooled
  4. extractionextracted with diethyl 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-98f349e22971404c8df68a78d534f2bf
Source dataset
uspto-grants-2015_12
Patent number
US09199943B2

Reaction notes

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