1-Bromo-3-chloro-5-fluorobenzene → 2-[(3-Bromo-5-chlorophenyl)oxy]-1-chloro-3-fluoro-4-methylbenzene

HRID 1875145Notes

Reaction equation

HRID 1875145 reaction equation
[Cl:1][C:2]1[C:7]([OH:8])=[C:6]([F:9])[C:5]([CH3:10])=[CH:4][CH:3]=1.CC(C)([O-])C.[K+].[Br:17][C:18]1[CH:23]=[C:22](F)[CH:21]=[C:20]([Cl:25])[CH:19]=1>CS(C)=O.CCOC(C)=O>[Br:17][C:18]1[CH:23]=[C:22]([O:8][C:7]2[C:6]([F:9])=[C:5]([CH3:10])[CH:4]=[CH:3][C:2]=2[Cl:1])[CH:21]=[C:20]([Cl:25])[CH:19]=1

Participants

6

Reactant 3

HCID 27362231-Bromo-3-chloro-5-fluorobenzeneHCID 27736846-Chloro-2-fluoro-3-methylphenolHCID 23665647Potassium tert-butoxide

Product 1

HCID 684866152-[(3-Bromo-5-chlorophenyl)oxy]-1-chloro-3-fluoro-4-methylbenzeneYield 57.2%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 6-chloro-2-fluoro-3-methylphenol (7.67 g, 47.7 mmol) in DMSO (100 ml) was added potassium t-butoxide (1.0 M solution in THF) (50.1 ml, 50.1 mmol) and the mixture was stirred at room temperature for 30 minutes. Next, 1-bromo-3-chloro-5-fluorobenzene (10.0 g, 47.7 mmol) was added and the mixture was heated at 135° C. for 3 days. The reaction mixture was cooled to room temperature, diluted with EtOAc and washed with water. The solvent was removed to give 2-[(3-bromo-5-chlorophenyl)oxy]-1-chloro-3-fluoro-4-methylbenzene (9.54 g, 27.3 mmol, 57% yield) which was used in the next step without further purification. 1H NMR (400 MHz, DMSO-d6) δ ppm 7.44 (s, 1H), 7.33-7.40 (m, 1H), 7.27 (t, 1H), 7.07 (s, 1H), 6.95-7.02 (m, 1H), 2.23 (d, 3H).

Workup

  1. temperaturethe mixture was heated at 135° C. for 3 days
  2. temperatureThe reaction mixture was cooled to room temperature
  3. washwashed with water
  4. customThe solvent was removed

Sources & evidence

ORD record
ord-22a94a675c3941e391d2068a221ad20c
Source dataset
uspto-grants-2012_11
Patent number
US08304419B2

Reaction notes

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