3-(Trifluoromethyl)phenol → 3-Chloro-2-(3-(trifluoromethyl)phenoxy)pyridine

HRID 566582Notes

Reaction equation

HRID 566582 reaction equation
[F:1][C:2]([F:11])([F:10])[C:3]1[CH:4]=[C:5]([OH:9])[CH:6]=[CH:7][CH:8]=1.Cl[C:13]1[C:18]([Cl:19])=[CH:17][CH:16]=[CH:15][N:14]=1>CN(C)C=O>[Cl:19][C:18]1[C:13]([O:9][C:5]2[CH:6]=[CH:7][CH:8]=[C:3]([C:2]([F:10])([F:11])[F:1])[CH:4]=2)=[N:14][CH:15]=[CH:16][CH:17]=1

Participants

4

Reactant 2

HCID 73763-(Trifluoromethyl)phenolHCID 169882,3-Dichloropyridine

Product 1

HCID 180084773-Chloro-2-(3-(trifluoromethyl)phenoxy)pyridine

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
120 °C

Procedure

7.68 g of sodium hydride dispersion (ca. 50 percent in mineral oil) was washed with pentane under nitrogen and 100 ml of N,N-dimethylformamide was then added. 21.92 g (135 mmol) of 3-(trifluoromethyl)phenol was added dropwise over 30 minutes at room temperature. The resultant phenate solution was added dropwise over 2 hours, under nitrogen, to a solution of 20.1 g (136 mmol) of 2,3-dichloropyridine in 80 ml of N,N-dimethylformamide, heated to 120° C. After a reaction time of 3 hours, the mixture was cooled to room temperature, the precipitate of sodium chloride was filtered off and the filtrate was concentrated. The residue was extracted with toluene and 0.1N hydrochloric acid and the organic phase was washed with saturated sodium chloride solution and concentrated. The oily residue was distilled under vacuum. The yield of the title compound was 24.75 g (67 percent) of a colorless oil, content (GC) 99.7 percent. Other data concerning the title compound was:

Workup

  1. wash7.68 g of sodium hydride dispersion (ca. 50 percent in mineral oil) was washed with pentane under nitrogen
  2. addition100 ml of N,N-dimethylformamide was then added
  3. temperatureAfter a reaction time of 3 hours, the mixture was cooled to room temperature
  4. filtrationthe precipitate of sodium chloride was filtered off
  5. concentrationthe filtrate was concentrated
  6. extractionThe residue was extracted with toluene and 0.1N hydrochloric acid
  7. washthe organic phase was washed with saturated sodium chloride solution
  8. concentrationconcentrated
  9. distillationThe oily residue was distilled under vacuum

Sources & evidence

ORD record
ord-8fa5951e29814a2f8f13a8276bbeba29
Source dataset
uspto-grants-2001_01
Patent number
US06175011B1

Reaction notes

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