Sodium Hydroxide → 1-(2-Chloro-4-fluorophenyl)2-(5-trifluoromethyl-2-pyridinyl)ethanone

HRID 354248Notes

Reaction equation

HRID 354248 reaction equation
[H-].[Na+].Cl[C:4]1[CH:9]=[CH:8][C:7]([C:10]([F:13])([F:12])[F:11])=[CH:6][N:5]=1.[CH3:14][C:15]([C:17]1[CH:22]=[CH:21][C:20]([F:23])=[CH:19][C:18]=1[Cl:24])=[O:16].[OH-].[Na+]>COCCOC>[Cl:24][C:18]1[CH:19]=[C:20]([F:23])[CH:21]=[CH:22][C:17]=1[C:15](=[O:16])[CH2:14][C:4]1[CH:9]=[CH:8][C:7]([C:10]([F:13])([F:12])[F:11])=[CH:6][N:5]=1

Participants

6

Reactant 4

HCID 14798Sodium HydroxideHCID 24758Sodium hydrideHCID 923422-Chloro-5-(trifluoromethyl)pyridineHCID 27365072'-Chloro-4'-fluoroacetophenone

Product 1

HCID 235133431-(2-Chloro-4-fluorophenyl)2-(5-trifluoromethyl-2-pyridinyl)ethanoneYield 67%

Reagents, catalysts & solvents 1

HCID 80711,2-DimethoxyethaneSolvent2×

Procedure

A reaction vessel was charged with sodium hydride (as a 60% oil dispersion, 5.0 g, 125 mmol), DME (40 ml) and 2-chloro-5-trifluoromethylpyridine (6.93 g, 38.2 mmol). 2-Chloro-4-fluoroacetophenone (6.8 g, 39.4 mmol) in DME (10 ml) was added in portions to the mixture under nitrogen at room temperature. The mixture was stirred at ambient temperature for one hour then at 40-45° C. overnight. Upon the completion of the reaction, the mixture was cooled to 5° C. and 10% aqueous sodium hydroxide solution (20 ml) was slowly added to the reaction mixture. The mixture was partitioned between diethylether (300 ml) and water (300 ml). The layers were separated, the organics dried over magnesium sulfate and concentrated to dryness. The residue was purified by column chromatography on silica eluting with diethylether-cyclohexane (1:3). Concentration of the appropriate fractions afforded 8.10 g (67%) of the title compound.

Workup

  1. customat 40-45° C.
  2. customovernight
  3. customUpon the completion of the reaction
  4. temperaturethe mixture was cooled to 5° C.
  5. customThe mixture was partitioned between diethylether (300 ml) and water (300 ml)
  6. customThe layers were separated
  7. dry with materialthe organics dried over magnesium sulfate
  8. concentrationconcentrated to dryness
  9. customThe residue was purified by column chromatography on silica eluting with diethylether-cyclohexane (1:3)

Sources & evidence

ORD record
ord-8ed8c08550b9403abfd323dccabec7f2
Source dataset
uspto-grants-2004_06
Patent number
US06756498B2

Reaction notes

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