Potassium Carbonate → 7-(2,5-Dichlorothiophen-3-yl)-4-trifluoromethyl-5,6,7,8-tetrahydrocinnolin-5-one

HRID 1700648Notes

Reaction equation

HRID 1700648 reaction equation
[Cl:1][C:2]1[S:3][C:4]([Cl:26])=[CH:5][C:6]=1[CH:7]1[CH2:12][C:11]([NH:13][NH:14]S(C2C=CC(C)=CC=2)(=O)=O)=[CH:10][C:9](=[O:25])[CH2:8]1.C(=O)([O-])[O-].[K+].[K+].Br[CH2:34][C:35](=O)[C:36]([F:39])([F:38])[F:37]>CO>[Cl:1][C:2]1[S:3][C:4]([Cl:26])=[CH:5][C:6]=1[CH:7]1[CH2:12][C:11]2[N:13]=[N:14][CH:34]=[C:35]([C:36]([F:39])([F:38])[F:37])[C:10]=2[C:9](=[O:25])[CH2:8]1

Participants

5

Reactant 3

HCID 11430Potassium Carbonate2×HCID 790083-Bromo-1,1,1-trifluoro-2-propanoneHCID 183175305-(2,5-Dichlorothiophen-3-yl)-1-[2-(4-methylphenylsulfonyl)hydrazino]cyclohexen-3-one

Product 1

HCID 183174187-(2,5-Dichlorothiophen-3-yl)-4-trifluoromethyl-5,6,7,8-tetrahydrocinnolin-5-oneYield 50.9%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a mixture of 5-(2,5-dichlorothiophen-3-yl)-1-[2-(4-methylphenylsulfonyl)hydrazino]cyclohexen-3-one (2.0 g), anhydrous potassium carbonate (0.9 g) and methanol (20 ml) was added, under ice-cooling, 1-bromo-3,3,3-trifluoropropan-2-one (1.24 g), and the mixture was stirred at the same temperature for 0.5 hours. To the mixture was added anhydrous potassium carbonate (1.2 g), and the mixture was refluxed for 2 hours. Under reduced pressure, the solvent was evaporated, and the residue was extracted with ethyl acetate. The organic layer was concentrated, and the residue was dissolved in acetic acid (15 ml). To the solution was added concentrated sulfuric acid (0.6 ml), and the mixture was refluxed for 30 minutes. To the reaction solution was added water (120 ml), and the mixture was concentrated under reduced pressure. The residue was extracted with ethyl acetate, and the organic layer was washed with sodium hydrogen carbonate solution and concentrated. The residue was purified with silica gel column chromatography to give 7-(2,5-dichlorothiophen-3-yl)-4-trifluoromethyl-5,6,7,8-tetrahydrocinnolin-5-one (0.867 g) as oil.

Workup

  1. additionwas added, under ice-
  2. temperaturecooling
  3. temperaturethe mixture was refluxed for 2 hours
  4. customUnder reduced pressure, the solvent was evaporated
  5. extractionthe residue was extracted with ethyl acetate
  6. concentrationThe organic layer was concentrated
  7. dissolutionthe residue was dissolved in acetic acid (15 ml)
  8. additionTo the solution was added concentrated sulfuric acid (0.6 ml)
  9. temperaturethe mixture was refluxed for 30 minutes
  10. additionTo the reaction solution was added water (120 ml)
  11. concentrationthe mixture was concentrated under reduced pressure
  12. extractionThe residue was extracted with ethyl acetate
  13. washthe organic layer was washed with sodium hydrogen carbonate solution
  14. concentrationconcentrated
  15. customThe residue was purified with silica gel column chromatography

Sources & evidence

ORD record
ord-8c6f491c77174a66a5fa6ba82387f764
Source dataset
uspto-grants-2002_02
Patent number
US06350749B1

Reaction notes

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