Dabco → 1-(4-Fluorophenyl)-2-oxo-6-(trifluoromethyl)-1,2-dihydropyridine-3-carbonitrile

HRID 2095853Notes

Reaction equation

HRID 2095853 reaction equation
[C:1]([CH2:3][C:4]([NH:6][C:7]1[CH:12]=[CH:11][C:10]([F:13])=[CH:9][CH:8]=1)=[O:5])#[N:2].C(O/[CH:17]=[CH:18]/[C:19](=O)[C:20]([F:23])([F:22])[F:21])C.N12CCN(CC1)CC2>COCCO.Cl.C(OCC)(=O)C>[F:13][C:10]1[CH:9]=[CH:8][C:7]([N:6]2[C:19]([C:20]([F:23])([F:22])[F:21])=[CH:18][CH:17]=[C:3]([C:1]#[N:2])[C:4]2=[O:5])=[CH:12][CH:11]=1

Participants

7

Reactant 3

HCID 9237DabcoHCID 6931482-Cyano-N-(4-fluorophenyl)acetamideHCID 5709222(3E)-4-Ethoxy-1,1,1-trifluoro-3-buten-2-one

Product 1

HCID 581584831-(4-Fluorophenyl)-2-oxo-6-(trifluoromethyl)-1,2-dihydropyridine-3-carbonitrileYield 7.3%

Reagents, catalysts & solvents 3

HCID 313Hydrochloric AcidSolventHCID 80192-MethoxyethanolSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
120 °C

Procedure

To a solution of 2-cyano-N-(4-fluorophenyl)acetamide (2 g, 11.2 mmol) and (3E)-4-ethoxy-1,1,1-trifluorobut-3-en-2-one (2.26 g, 13.4 mmol) in dimethyleneglycol monomethylether (20 mL) was added 1,4-diazabicyclo[2.2.2]octane (1.26 g, 11.2 mmol), and the mixture was stirred at 120° C. for 6 hr. The reaction mixture was diluted with 1N hydrochloric acid and ethyl acetate, and the mixture was extracted 3 times with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate and filtered. The solvent was evaporated under reduced pressure. The obtained residue was purified by silica gel column chromatography (NH silica gel, ethyl acetate/hexane=1/2→1/1) to give a white solid. The white solid was washed with ethyl acetate and collected by filtration to give the title compound (230 mg, 7.2%) as a white solid.

Workup

  1. extractionthe mixture was extracted 3 times with ethyl acetate
  2. washThe organic layer was washed with saturated brine
  3. dry with materialdried over anhydrous magnesium sulfate
  4. filtrationfiltered
  5. customThe solvent was evaporated under reduced pressure
  6. customThe obtained residue was purified by silica gel column chromatography (NH silica gel, ethyl acetate/hexane=1/2→1/1)
  7. customto give a white solid
  8. washThe white solid was washed with ethyl acetate
  9. filtrationcollected by filtration

Sources & evidence

ORD record
ord-479ff93a4f734902bc4102c156dd5156
Source dataset
uspto-grants-2013_05
Patent number
US08445509B2

Reaction notes

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