Malononitrile → 2-amino-1-(4-bromo-2,6-dimethylphenyl)-4-methyl-5-oxo-4,5-dihydro-1H-pyrrole-3-carbonitrile

HRID 1253828Notes

Reaction equation

HRID 1253828 reaction equation
[H-].[Na+].[C:3](#[N:7])[CH2:4][C:5]#[N:6].Br[CH:9]([CH3:22])[C:10]([NH:12][C:13]1[C:18]([CH3:19])=[CH:17][C:16]([Br:20])=[CH:15][C:14]=1[CH3:21])=[O:11].[Cl-].[NH4+]>O1CCCC1>[NH2:6][C:5]1[N:12]([C:13]2[C:18]([CH3:19])=[CH:17][C:16]([Br:20])=[CH:15][C:14]=2[CH3:21])[C:10](=[O:11])[CH:9]([CH3:22])[C:4]=1[C:3]#[N:7]

Participants

6

Reactant 4

HCID 8010MalononitrileHCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 600353552-bromo-N-(4-bromo-2,6-dimethylphenyl)propionamide

Product 1

HCID 671036822-amino-1-(4-bromo-2,6-dimethylphenyl)-4-methyl-5-oxo-4,5-dihydro-1H-pyrrole-3-carbonitrileYield 96%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a suspension of NaH (17.2 g) in tetrahydrofuran (500 mL) was added a solution of malononitrile (28.4 g) in tetrahydrofuran (100 mL) under ice-cooling and the mixture was stirred at room temperature for 1 hour. 2-Bromo-N-(4-bromo-2,6-dimethylphenyl)propionamide (120 g) was added and the mixture was heated at reflux for 1 hour. With ice-cooling, an ammonium chloride aqueous solution was added and extracted with ethyl acetate. The organic layer was washed with brine, dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated under reduced pressure to give a solid. The solid was washed with a mixture of diisopropylether and ethyl acetate and filtered, dried to give 2-amino-1-(4-bromo-2,6-dimethylphenyl)-4-methyl-5-oxo-4,5-dihydro-1H-pyrrole-3-carbonitrile (110.1 g).

Workup

  1. temperaturecooling
  2. temperaturethe mixture was heated
  3. temperatureat reflux for 1 hour
  4. temperatureWith ice-cooling
  5. extractionextracted with ethyl acetate
  6. washThe organic layer was washed with brine
  7. dry with materialdried over anhydrous sodium sulfate
  8. filtrationfiltered
  9. concentrationThe filtrate was concentrated under reduced pressure
  10. customto give a solid
  11. washThe solid was washed with a mixture of diisopropylether and ethyl acetate
  12. filtrationfiltered
  13. customdried

Sources & evidence

ORD record
ord-d7ccaa947a30472094bbdd663e11d824
Source dataset
uspto-grants-2013_06
Patent number
US08455511B2

Reaction notes

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