Dabco → 1-(2,4-Difluorophenyl)-6-methyl-2-oxo-1,2-dihydropyridine-3-carbonitrile

HRID 2095851Notes

Reaction equation

HRID 2095851 reaction equation
[C:1]([CH2:3][C:4]([NH:6][C:7]1[CH:12]=[CH:11][C:10]([F:13])=[CH:9][C:8]=1[F:14])=[O:5])#[N:2].CO/[CH:17]=[CH:18]/[C:19](=O)[CH3:20].N12CCN(CC1)CC2>COCCO.Cl.O1CCCC1.C(OCC)(=O)C>[F:14][C:8]1[CH:9]=[C:10]([F:13])[CH:11]=[CH:12][C:7]=1[N:6]1[C:19]([CH3:20])=[CH:18][CH:17]=[C:3]([C:1]#[N:2])[C:4]1=[O:5]

Participants

8

Reactant 3

HCID 9237DabcoHCID 639675(3E)-4-Methoxy-3-buten-2-oneHCID 7375122-cyano-N-(2,4-difluorophenyl)acetamide

Product 1

HCID 581584621-(2,4-Difluorophenyl)-6-methyl-2-oxo-1,2-dihydropyridine-3-carbonitrileYield 9.4%

Reagents, catalysts & solvents 4

HCID 313Hydrochloric AcidSolventHCID 80192-MethoxyethanolSolventHCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
120 °C

Procedure

To a solution of 2-cyano-N-(2,4-difluorophenyl)acetamide (5.5 g, 28 mmol) and (3E)-4-methoxybut-3-en-2-one (3.65 g, 36.5 mmol) in dimethyleneglycol monomethylether (50 mL) was added 1,4-diazabicyclo[2.2.2]octane (3.14 g, 28 mmol), and the mixture was stirred at 120° C. for 12 hr. The reaction mixture was diluted with 2N hydrochloric acid, tetrahydrofuran and ethyl acetate, and 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 washed with ethyl acetate to give a slightly yellow solid. The slightly yellow solid was suspended in tetrahydrofuran at 80° C., and the suspension was stirred for 30 min. The suspension was filtrated, and the obtained solid was washed with tetrahydrofuran to give the title compound (650 mg, 9.4%) as a white solid.

Workup

  1. extractionextracted 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. washThe obtained residue was washed with ethyl acetate
  7. customto give a slightly yellow solid
  8. stirringthe suspension was stirred for 30 min
  9. filtrationThe suspension was filtrated
  10. washthe obtained solid was washed with tetrahydrofuran

Sources & evidence

ORD record
ord-93b22f8105d94c18b026de6b677b93d2
Source dataset
uspto-grants-2013_05
Patent number
US08445509B2

Reaction notes

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