Ammonia → 6-Methyl-3-phenylquinolin-2(1H)-one

HRID 1357770Notes

Reaction equation

HRID 1357770 reaction equation
[CH3:1]N(C)C=O.O=P(Cl)(Cl)Cl.[CH3:11][C:12]1[CH:17]=[CH:16][C:15]([NH:18][C:19](=[O:27])[CH2:20][C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)=[CH:14][CH:13]=1.N>C(O)(=O)C.O>[CH3:11][C:12]1[CH:17]=[C:16]2[C:15](=[CH:14][CH:13]=1)[NH:18][C:19](=[O:27])[C:20]([C:21]1[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=1)=[CH:1]2

Participants

7

Reactant 4

HCID 222AmmoniaHCID 6228DimethylformamideHCID 24813Phosphorus oxychlorideHCID 854300N-(4-methylphenyl)-2-phenylacetamide

Product 1

HCID 125588576-Methyl-3-phenylquinolin-2(1H)-oneYield 10%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 962WaterSolvent

Conditions

Temperature
-30 °C

Procedure

0.41 ml (5.3 mmol, 1.5 eq) of N,N-dimethylformamide is added dropwise to 3.3 ml (25 mmol, 7 eq) of POCl3, under a nitrogen atmosphere and at −30° C. The medium is stirred for 15 min at −30° C. and 800 mg of amide 47 (3.5 mmol) are then added. The reaction mixture is warmed to room temperature with stirring and the reaction is then heated at 75° C. for 1.5 h. At the end of the reaction, this solution is poured onto crushed ice, neutralized with aqueous 30% ammonia solution and then extracted with dichloromethane. The organic phase is dried over MgSO4 and then evaporated. The residue obtained is dissolved in 5.4 ml of glacial acetic acid and 0.2 ml of water and the final solution is then refluxed for 3 h. The acetic acid is evaporated off. The residue is dissolved in water, neutralized with 25% sodium hydroxide solution and then finally extracted with dichloromethane. The organic phase is dried over MgSO4 and then evaporated under reduced pressure. The residue is taken up in ethyl acetate, which brings about precipitation of the final product. The crystals thus obtained are filtered off to give 80 mg (10%) of compound 48.

Workup

  1. temperatureThe reaction mixture is warmed to room temperature
  2. stirringwith stirring
  3. temperaturethe reaction is then heated at 75° C. for 1.5 h
  4. customAt the end of the reaction
  5. additionthis solution is poured
  6. customonto crushed ice
  7. extractionextracted with dichloromethane
  8. dry with materialThe organic phase is dried over MgSO4
  9. customevaporated
  10. customThe residue obtained
  11. customThe acetic acid is evaporated off
  12. dissolutionThe residue is dissolved in water
  13. extractionfinally extracted with dichloromethane
  14. dry with materialThe organic phase is dried over MgSO4
  15. customevaporated under reduced pressure
  16. customwhich brings about precipitation of the final product
  17. customThe crystals thus obtained
  18. filtrationare filtered off

Sources & evidence

ORD record
ord-50097923fa744a549f8b4e21d4597f8b
Source dataset
uspto-grants-2003_07
Patent number
US06593342B1

Reaction notes

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