Water → 5,5-Dimethyl-1-(6-methoxyquinolin-4-ylmethyl)-3-(4-trifluoromethoxyphenyl)imidazolidine-2,4-dione

HRID 899965Notes

Reaction equation

HRID 899965 reaction equation
[H-].[Na+].[CH3:3][C:4]1([CH3:22])[NH:8][C:7](=[O:9])[N:6]([C:10]2[CH:15]=[CH:14][C:13]([O:16][C:17]([F:20])([F:19])[F:18])=[CH:12][CH:11]=2)[C:5]1=[O:21].Cl[CH2:24][C:25]1[C:34]2[C:29](=[CH:30][CH:31]=[C:32]([O:35][CH3:36])[CH:33]=2)[N:28]=[CH:27][CH:26]=1.O>C1COCC1.C(OCC)(=O)C>[CH3:3][C:4]1([CH3:22])[N:8]([CH2:24][C:25]2[C:34]3[C:29](=[CH:30][CH:31]=[C:32]([O:35][CH3:36])[CH:33]=3)[N:28]=[CH:27][CH:26]=2)[C:7](=[O:9])[N:6]([C:10]2[CH:15]=[CH:14][C:13]([O:16][C:17]([F:20])([F:19])[F:18])=[CH:12][CH:11]=2)[C:5]1=[O:21]

Participants

7

Reactant 4

HCID 962WaterHCID 24758Sodium hydrideHCID 132680675,5-Dimethyl-3-[4-(trifluoromethoxy)phenyl]imidazolidine-2,4-dioneHCID 179006174-(Chloromethyl)-6-methoxy-quinoline

Product 1

HCID 596942685,5-Dimethyl-1-(6-methoxyquinolin-4-ylmethyl)-3-(4-trifluoromethoxyphenyl)imidazolidine-2,4-dioneYield 34.7%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

0.1 g of sodium hydride (at 60%) is added to a solution of 0.65 g of 5,5-dimethyl-3-(4-trifluoromethoxyphenyl)imidazolidine-2,4-dione in 40 ml of anhydrous THF, under an inert atmosphere of argon at a temperature in the region of 20° C. Stirring is maintained at this temperature for 30 minutes. 0.47 g of 4-chloromethyl-6-methoxyquinoline dissolved in 10 ml of THF is added. The reaction medium is refluxed for 16 hours. After cooling, 100 ml of water and 75 ml of ethyl acetate are added. After separation of the phases by settling, the organic phase is dried over sodium sulfate, filtered and then concentrated under reduced pressure. The brown oil obtained is purified by flash chromatography (SiO2, EtOAc/cyclohexane, 50/50 by volume, as eluent, Ar). The fractions containing the product are concentrated under reduced pressure. 0.36 g of 5,5-dimethyl-1-(6-methoxyquinolin-4-ylmethyl)-3-(4-trifluoromethoxyphenyl)imidazolidine-2,4-dione is thus obtained, the characteristics of which product are as follows:

Workup

  1. temperatureis maintained at this temperature for 30 minutes
  2. additionis added
  3. temperatureThe reaction medium is refluxed for 16 hours
  4. temperatureAfter cooling
  5. customAfter separation of the phases
  6. dry with materialthe organic phase is dried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customThe brown oil obtained
  10. customis purified by flash chromatography (SiO2, EtOAc/cyclohexane, 50/50 by volume, as eluent, Ar)
  11. additionThe fractions containing the product
  12. concentrationare concentrated under reduced pressure

Sources & evidence

ORD record
ord-2f4e1175186049d4a006854feae08b45
Source dataset
uspto-grants-2008_04
Patent number
US07354933B2

Reaction notes

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