Toluene → 7-(2,5-Difluorophenyl)-4-methyl-5,6,7,8-tetrahydroquinolin-5-one

HRID 49206Notes

Reaction equation

HRID 49206 reaction equation
[NH2:1][CH:2]1[CH2:7][CH:6]([C:8]2[CH:13]=[C:12]([F:14])[CH:11]=[CH:10][C:9]=2[F:15])[CH2:5][C:4](=[O:16])[CH2:3]1.[C:17]1(C)[CH:22]=CC=[CH:19][CH:18]=1.[OH-].[K+]>C(O)C>[F:15][C:9]1[CH:10]=[CH:11][C:12]([F:14])=[CH:13][C:8]=1[CH:6]1[CH2:7][C:2]2[N:1]=[CH:22][CH:17]=[C:18]([CH3:19])[C:3]=2[C:4](=[O:16])[CH2:5]1

Participants

5

Reactant 3

HCID 1140TolueneHCID 14797Potassium Hydroxide4×HCID 178239181-Amino-5-(2,5-difluorophenyl)cyclohexan-3-one

Product 1

HCID 110869317-(2,5-Difluorophenyl)-4-methyl-5,6,7,8-tetrahydroquinolin-5-one

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

A mixture of 1-amino-5-(2,5-difluorophenyl)cyclohexan-3-one (3.7 g), 3-oxobutylaldehyde dimethyl acetal (5.5 g), toluene (120 ml) and ethanol (70 ml) was stirred at 115° C. with adding potassium hydroxide powder (0.77 g). The mixture was combined with potassium hydroxide powder (0.16 g) after 30 minutes and with potassium hydroxide powder (0.16 g) and 3-oxobutylaldehyde dimethyl acetal (0.44 g) after 1 hour and further with potassium hydroxide powder (0.16 g) after 1 hour and 30 minutes, and then stirred at the same temperature for 5 hours. After cooling, the solvent was distilled off under reduced pressure and ethyl acetate was added. The organic layer was washed successively with water and saturated brine, and dried over magnesium sulfate. Ethyl acetate was distilled off under reduced pressure, and the residue was subjected to a silica gel column (ethyl acetate-hexane), and the resultant crystal was recrystallized from ethyl acetate-hexane to obtain 7-(2,5-difluorophenyl)-4-methyl-5,6,7,8-tetrahydroquinolin-5-one (2.3 g).

Workup

  1. temperatureAfter cooling
  2. distillationthe solvent was distilled off under reduced pressure and ethyl acetate
  3. additionwas added
  4. washThe organic layer was washed successively with water and saturated brine
  5. dry with materialdried over magnesium sulfate
  6. distillationEthyl acetate was distilled off under reduced pressure
  7. customthe resultant crystal was recrystallized from ethyl acetate-hexane

Sources & evidence

ORD record
ord-3fe9e8daa96740db9eec1b3ce3c7b005
Source dataset
uspto-grants-2004_03
Patent number
US06706732B1

Reaction notes

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