Diisopropylamine → 4-(Trifluoromethyl)-6-[4-(methylthio)phenyl]-2-pyridone

HRID 268600Notes

Reaction equation

HRID 268600 reaction equation
C(NC(C)C)(C)C.C([Li])CCC.[F:13][C:14]([F:22])([F:21])[C:15]([CH3:20])=[CH:16][C:17](O)=[O:18].[CH3:23][S:24][C:25]1[CH:32]=[CH:31][C:28]([C:29]#[N:30])=[CH:27][CH:26]=1>C1COCC1.O>[F:13][C:14]([F:22])([F:21])[C:15]1[CH:20]=[C:29]([C:28]2[CH:31]=[CH:32][C:25]([S:24][CH3:23])=[CH:26][CH:27]=2)[NH:30][C:17](=[O:18])[CH:16]=1

Participants

7

Reactant 4

HCID 7912DiisopropylamineHCID 1443384,4,4-Trifluoro-3-methylbut-2-enoic acidHCID 5909604-(Methylthio)benzonitrileHCID 178418339Butyllithium

Product 1

HCID 586039774-(Trifluoromethyl)-6-[4-(methylthio)phenyl]-2-pyridoneYield 43.7%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent3×

Procedure

To a stirred solution of diisopropylamine (11.5 mL, 81.8 mmol) in THF (75 mL) at 0° C. was added n-butyllithium (51.1 mL of a 1.6M solution in hexanes, 81.8 mmol). After stirring for 15 minutes, a solution of 4,4,4-trifluoro-3-methyl-2-butenoic acid (6.0 g, 38.9 mmol) in THF (10 mL) was added dropwise. The reaction was allowed to warm to room temperature and stirred for 30 minutes before being cooled to 0° C. and treated dropwise with a solution of 4-(methylthio)benzonitrile (2.91 g, 19.5 mmol) in THF (10 mL). Upon complete addition, the reaction was heated at reflux for 14 hours. After cooling, water (200 mL) was added and the mixture extracted with ethyl acetate (250 mL). The organic phase was dried over sodium sulfate, filtered and concentrated in vacuo and the resulting residue purified by silica chromatography eluting with 1:1 ethyl acetate/cyclohexane to give the title product (2.43 g) LC retention time 3.10 mins MS m/z 286 (MH+).

Workup

  1. stirringstirred for 30 minutes
  2. temperaturebefore being cooled to 0° C.
  3. additionUpon complete addition
  4. temperaturethe reaction was heated
  5. temperatureat reflux for 14 hours
  6. temperatureAfter cooling
  7. extractionthe mixture extracted with ethyl acetate (250 mL)
  8. dry with materialThe organic phase was dried over sodium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo
  11. customthe resulting residue purified by silica chromatography
  12. washeluting with 1:1 ethyl acetate/cyclohexane

Sources & evidence

ORD record
ord-7254de3c22d74a88b05eb8ca05ec00e5
Source dataset
uspto-grants-2008_11
Patent number
US07446117B2

Reaction notes

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