1,3-Cyclohexanedione → 4-(3-Trifluoromethoxyphenyl)-2-methyl-4,6,7,8-tetrahydro-5(1H)-quinolone

HRID 54455Notes

Reaction equation

HRID 54455 reaction equation
[F:1][C:2]([F:13])([F:12])[O:3][C:4]1[CH:5]=[C:6]([CH:9]=[CH:10][CH:11]=1)[CH:7]=O.[C:14]1(=[O:21])[CH2:19][CH2:18][CH2:17][C:16](=O)[CH2:15]1.[C:22]([O-])(=O)C.[NH4+].[NH:27]1[CH2:31][CH2:30]CC1>C(O)C.O.C(O)(=O)C.CC(C)=O>[F:1][C:2]([F:13])([F:12])[O:3][C:4]1[CH:5]=[C:6]([CH:7]2[C:15]3[C:14](=[O:21])[CH2:19][CH2:18][CH2:17][C:16]=3[NH:27][C:31]([CH3:30])=[CH:22]2)[CH:9]=[CH:10][CH:11]=1

Participants

9

Reactant 4

HCID 104341,3-CyclohexanedioneHCID 31268PyrrolidineHCID 517165Ammonium AcetateHCID 6051393-(Trifluoromethoxy)benzaldehyde

Product 1

HCID 199589324-(3-Trifluoromethoxyphenyl)-2-methyl-4,6,7,8-tetrahydro-5(1H)-quinoloneYield 13.9%

Reagents, catalysts & solvents 4

HCID 176Acetic AcidSolventHCID 180AcetoneSolventHCID 702EthanolSolvent2×HCID 962WaterSolvent

Procedure

A solution of 3-(trifluoromethoxy)benzaldehyde (10.00 g) and 1,3-cyclohexanedione (5.90 g) in ethanol (50 mL) was stirred at reflux for 3 hours. Ammonium acetate (6.09 g) and acetone (3.67 g) were added to the cooled mixture, followed by a solution of acetic acid (3.79 g) and pyrrolidine (4.49 g) in ethanol (15 mL). The mixture was stirred at reflux overnight, poured into water and extracted with ethyl acetate (2×200 mL). The combined organics were dried and concentrated to an oil which was purified by chromatography (0-40% v/v ethyl acetate in methylene chloride) to yield the title compound (2.36 g) as an off-white solid, mp 144°-146° C.; NMR: 1.74 (s,3, CH3), 1.78-1.92 (m,2, CH2), 2.14-2.19 (m,2, CH2) 2.42-2.47 (m,2, CH2) 4.46 (d,1, J=4.8, CH) 4.63 (d,1, J=4.9, CH) 7.01-7.05 (m,2, Ar) 7.17 (d,1, J=7.7, Ar) 7.36 (dd,1, J=7.7, 3.2, Ar), 8.52 (s,1, NH); (CI, CH4) MS: m/z=324(M+1). Analysis for C17H16NO2F3:Calculated: C, 63.15; H, 4.99; N, 4.33; Found: C, 62.88; H, 5.05; N, 4.33.

Workup

  1. temperatureat reflux for 3 hours
  2. temperatureat reflux overnight
  3. extractionextracted with ethyl acetate (2×200 mL)
  4. customThe combined organics were dried
  5. concentrationconcentrated to an oil which
  6. customwas purified by chromatography (0-40% v/v ethyl acetate in methylene chloride)

Sources & evidence

ORD record
ord-2c0a73fedd684f7d847d60aa333895ff
Source dataset
uspto-grants-1997_04
Patent number
US05622964

Reaction notes

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