p-Toluenesulfonic acid → 1-Methyl-5-[2-(4-trifluoromethyl-phenyl)-ethylamino]-5,6,7,8-tetrahydro-1H-quinolin-2-one

HRID 1195172Notes

Reaction equation

HRID 1195172 reaction equation
[F:1][C:2]([F:13])([F:12])[C:3]1[CH:8]=[CH:7][C:6]([CH2:9][CH2:10][NH2:11])=[CH:5][CH:4]=1.[CH3:14][N:15]1[C:24]2[CH2:23][CH2:22][CH2:21][C:20](=O)[C:19]=2[CH:18]=[CH:17][C:16]1=[O:26].C1(C)C=CC(S(O)(=O)=O)=CC=1>C1(C)C=CC=CC=1>[F:1][C:2]([F:12])([F:13])[C:3]1[CH:4]=[CH:5][C:6]([CH2:9][CH2:10][NH:11][CH:20]2[CH2:21][CH2:22][CH2:23][C:24]3[N:15]([CH3:14])[C:16](=[O:26])[CH:17]=[CH:18][C:19]2=3)=[CH:7][CH:8]=1

Participants

5

Reactant 3

HCID 6101p-Toluenesulfonic acidHCID 19881062-[4-(Trifluoromethyl)phenyl]ethan-1-amineHCID 104422421-Methyl-7,8-dihydroquinoline-2,5(1H,6H)-dione

Product 1

HCID 103379341-Methyl-5-[2-(4-trifluoromethyl-phenyl)-ethylamino]-5,6,7,8-tetrahydro-1H-quinolin-2-oneYield 65%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

A mixture of 2-(4-trifluoromethylphenyl)ethylamine (4.1 g), 5,6,7,8-tetrahydro-1-methyl-5oxo-2(1H)-quinolinone (3.0 g), and para-toluenesulfonic acid (256 mg) was heated in refluxing toluene (50 ml), with azeotropic removal or water, for 40 hrs. An additional 2.0 g of the amine was added and the mixture was refluxed for 36 hr. The solution was cooled, and the mixture was concentrated in vacuo. Sodium borohydride (0.6 g) was added to a solution of the residue in ethyl alcohol (50 ml), and the resulting mixture was stirred at room temperature for 1 hr. The mixture was concentrated in vacuo, the residue was quenched with water, and the mixture was extracted with dichloromethane. The combined organic layers were washed with brine, dried over anhydrous magnesium sulfate, filtered, and the filtrate was concentrated. The residue was recrystallized from ethyl acetate/hexanes to provide, in two crops, 3.8 g (65%) of product, mp 104°-106° C.

Workup

  1. temperaturewas heated
  2. customwith azeotropic removal or water
  3. additionAn additional 2.0 g of the amine was added
  4. temperaturethe mixture was refluxed for 36 hr
  5. temperatureThe solution was cooled
  6. concentrationthe mixture was concentrated in vacuo
  7. additionSodium borohydride (0.6 g) was added to a solution of the residue in ethyl alcohol (50 ml)
  8. concentrationThe mixture was concentrated in vacuo
  9. customthe residue was quenched with water
  10. extractionthe mixture was extracted with dichloromethane
  11. washThe combined organic layers were washed with brine
  12. dry with materialdried over anhydrous magnesium sulfate
  13. filtrationfiltered
  14. concentrationthe filtrate was concentrated
  15. customThe residue was recrystallized from ethyl acetate/hexanes

Sources & evidence

ORD record
ord-0bc2d6547f514ef3b9ef0903c9b4a9eb
Source dataset
uspto-grants-1992_05
Patent number
US05110815

Reaction notes

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