Acetonitrile → 5,5-Dimethyl-1-(2-chloropyrid-4-ylmethyl)-3-(4-trifluoromethoxyphenyl)imidazolidine-2,4-dione

HRID 899974Notes

Reaction equation

HRID 899974 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:23][C:24]1[CH:29]=[C:28]([CH2:30]Br)[CH:27]=[CH:26][N:25]=1.C(#N)C>CN(C)C=O.O>[CH3:3][C:4]1([CH3:22])[N:8]([CH2:30][C:28]2[CH:27]=[CH:26][N:25]=[C:24]([Cl:23])[CH:29]=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 6342AcetonitrileHCID 24758Sodium hydrideHCID 129548074-(Bromomethyl)-2-chloropyridineHCID 132680675,5-Dimethyl-3-[4-(trifluoromethoxy)phenyl]imidazolidine-2,4-dione

Product 1

HCID 596942465,5-Dimethyl-1-(2-chloropyrid-4-ylmethyl)-3-(4-trifluoromethoxyphenyl)imidazolidine-2,4-dioneYield 69.7%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent2×

Procedure

0.028 g of sodium hydride is added to a solution of 0.1 g of 5,5-dimethyl-3-(4-trifluoromethoxyphenyl)imidazolidine-2,4-dione in 2 ml of anhydrous dimethylformamide, under an inert atmosphere of argon at a temperature in the region of 20° C. Stirring is continued at this temperature for 30 minutes. A solution of 0.1 g of 2-chloro-4-(bromomethyl)pyridine in 2 ml of dimethylformamide is added, followed by addition of ice-cold water after reaction for 10 minutes. The reaction medium is placed on a cartridge 20 mm in diameter packed with 17 g of octadecyl-grafted 50 μm silica conditioned successively with acetonitrile and then with water. The elution is performed by gradient using the mixture (water/acetonitrile) of from 0 to 100% acetonitrile. The fractions containing the expected product are concentrated under reduced pressure. 0.130 g of crude product is thus obtained, which product is purified by a double chromatography using a cartridge packed with 10 g of 20-40 μm of conditioned silica, and then eluted with a mixture (cyclohexane/ethyl acetate), (8/2) (v/v) at a flow rate of 5 ml/minute. The fractions between 30 and 75 ml are concentrated under reduced pressure. 0.1 g of 5,5-dimethyl-1-(2-chloropyrid-4-ylmethyl)-3-(4-trifluoromethoxyphenyl)imidazolidine-2,4-dione is thus obtained in the form of a white powder, the characteristics of which product are as follows:

Workup

  1. additionfollowed by addition of ice-cold water
  2. customafter reaction for 10 minutes
  3. washThe elution
  4. additionThe fractions containing the expected product
  5. concentrationare concentrated under reduced pressure
  6. custom0.130 g of crude product is thus obtained
  7. customwhich product is purified by a double chromatography
  8. washeluted with a mixture (cyclohexane/ethyl acetate), (8/2) (v/v) at a flow rate of 5 ml/minute
  9. concentrationThe fractions between 30 and 75 ml are concentrated under reduced pressure

Sources & evidence

ORD record
ord-80a0c0351a1c4c0a827f6e6d00c42c9f
Source dataset
uspto-grants-2008_04
Patent number
US07354933B2

Reaction notes

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