4'-Fluoroacetophenone → HCID 68550158, compound

HRID 731708Notes

Reaction equation

HRID 731708 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8](=O)[CH2:9][C:10]2[CH:15]=[CH:14][C:13]([C:16]([F:19])([F:18])[F:17])=[CH:12][N:11]=2)=[CH:4][CH:3]=1.C[C:22]([C:24]1[CH:29]=CC(F)=C[CH:25]=1)=[O:23].ClC1C=CC(C(F)(F)F)=C[N:33]=1.[H-].[Na+]>C1COCC1>[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:9]([C:22](=[O:23])[CH:24]([CH3:29])[CH3:25])=[C:10]3[CH:15]=[CH:14][C:13]([C:16]([F:19])([F:18])[F:17])=[CH:12][N:11]3[N:33]=2)=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 98284'-FluoroacetophenoneHCID 24758Sodium hydrideHCID 923422-Chloro-5-(trifluoromethyl)pyridineHCID 18987643Ethanone, 1-(4-fluorophenyl)-2-[5-(trifluoromethyl)-2-pyridinyl]-

Product 1

HCID 68550158HCID 68550158, compoundYield 79%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

1-(4-fluorophenyl)-2-(5-(trifluoromethyl)pyridin-2-yl)ethanone. To a solution of 4-fluoroacetophenone (13.8 g, 100 mmol) and 2-chloro-5-trifluoromethylpyridine (20.0 g, 110 mmol) in 400 ml of anhydrous THF was added NaH (5.56 g, 220 mmol) (washed with pentane prior to use) in several portions. The reaction was stirred under argon at room temperature for 3 days. The reaction was carefully quenched with H2O (300 ml), followed by addition of diethyl ether (200 ml). The organic layer was separated and extracted with 6N HCl (2×300 ml). The aqueous extracts were cooled to 0° C. and 6N NaOH was added dropwise to adjust the pH of the solution to pH 11-12. The mixture was then extracted with diethyl ether (4×150 ml) and the combined organic layers were then dried over MgSO4. Filtration and concentration furnished 22.4 g (79%) of the title compound as a tautomeric mixture.

Workup

  1. washwashed with pentane
  2. customThe reaction was carefully quenched with H2O (300 ml)
  3. additionfollowed by addition of diethyl ether (200 ml)
  4. customThe organic layer was separated
  5. extractionextracted with 6N HCl (2×300 ml)
  6. temperatureThe aqueous extracts were cooled to 0° C.
  7. addition6N NaOH was added dropwise
  8. extractionThe mixture was then extracted with diethyl ether (4×150 ml)
  9. dry with materialthe combined organic layers were then dried over MgSO4
  10. filtrationFiltration and concentration

Sources & evidence

ORD record
ord-a18da572edf548b1859b36100ed076ee
Source dataset
uspto-grants-2009_09
Patent number
US07585875B2

Reaction notes

Loading…