Sodium hydride → 5,5-Dimethyl-1-(2-bromopyrid-4-ylmethyl)-3-(4-trifluoromethoxyphenyl)imidazolidine-2,4-dione

HRID 899978Notes

Reaction equation

HRID 899978 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].[Br:23][C:24]1[CH:29]=[C:28]([CH2:30]Br)[CH:27]=[CH:26][N:25]=1.O.C(#N)C>CN(C)C=O>[CH3:3][C:4]1([CH3:22])[N:8]([CH2:30][C:28]2[CH:27]=[CH:26][N:25]=[C:24]([Br: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

6

Reactant 4

HCID 24758Sodium hydrideHCID 129548062-Bromo-4-(bromomethyl)pyridineHCID 132680675,5-Dimethyl-3-[4-(trifluoromethoxy)phenyl]imidazolidine-2,4-dioneHCID 18373917Acetonitrile--water (1/1)2×

Product 1

HCID 596942545,5-Dimethyl-1-(2-bromopyrid-4-ylmethyl)-3-(4-trifluoromethoxyphenyl)imidazolidine-2,4-dioneYield 11.6%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

0.023 g of sodium hydride is added to a solution of 0.081 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 35 minutes. A solution of 0.071 g of 2-bromo-4-(bromomethyl)pyridine in 1 ml of anhydrous dimethylformamide is added, followed by addition of ice-cold water after reaction for 15 minutes. The reaction mixture is placed on a cartridge 16 mm in diameter packed with 5 g of octadecyl-grafted 40-60 μm silica conditioned successively with the mixture (water/acetonitrile) (5/95) (v/v) and then the mixture (water/acetonitrile) (95/5) (v/v). The elution was performed with a linear gradient of from 5% to 95% of acetonitrile over 30 minutes then with a mixture (water/acetonitrile) (5/95) (v/v) over 10 minutes, at a flow rate of 5 ml/minute. The fractions between 90 and 100 ml are concentrated under reduced pressure. 0.015 g of 5,5-dimethyl-1-(2-bromopyrid-4-ylmethyl)-3-(4-trifluoromethoxyphenyl)-imidazolidine-2,4-dione is thus obtained in the form of a white foam, the characteristics of which product are as follows:

Workup

  1. additionfollowed by addition of ice-cold water
  2. customafter reaction for 15 minutes
  3. washThe elution
  4. waitwas performed with a linear gradient of from 5% to 95% of acetonitrile over 30 minutes
  5. waitwith a mixture (water/acetonitrile) (5/95) (v/v) over 10 minutes
  6. concentrationThe fractions between 90 and 100 ml are concentrated under reduced pressure

Sources & evidence

ORD record
ord-0419463d2229473397c16a249186d565
Source dataset
uspto-grants-2008_04
Patent number
US07354933B2

Reaction notes

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