Sodium hydride → 3-Cyclopropyl-1-(5-fluoro-2-trifluoromethyl-benzyl)-4-methyl-1,3-dihydro-imidazol-2-one

HRID 1092312Notes

Reaction equation

HRID 1092312 reaction equation
[CH:1]1([N:4]2[C:8]([CH3:9])=[CH:7][NH:6][C:5]2=[O:10])[CH2:3][CH2:2]1.[H-].[Na+].[F:13][C:14]([F:25])([F:24])[C:15]1[CH:22]=[CH:21][C:20]([F:23])=[CH:19][C:16]=1[CH2:17]Br>CN(C=O)C.[Cl-].[Na+].O>[CH:1]1([N:4]2[C:8]([CH3:9])=[CH:7][N:6]([CH2:17][C:16]3[CH:19]=[C:20]([F:23])[CH:21]=[CH:22][C:15]=3[C:14]([F:24])([F:13])[F:25])[C:5]2=[O:10])[CH2:3][CH2:2]1

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 27375785-Fluoro-2-(trifluoromethyl)benzyl bromideHCID 55300021Cyclopropyl-5-methyl-1,3-dihydro-imidazol-2-one

Product 1

HCID 249651543-Cyclopropyl-1-(5-fluoro-2-trifluoromethyl-benzyl)-4-methyl-1,3-dihydro-imidazol-2-oneYield 58.9%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent2×HCID 57417360Sodium chloride; waterSolvent

Procedure

Cyclopropyl-5-methyl-1,3-dihydro-imidazol-2-one (150 mg) was dissolved in DMF (5 mL) under argon and sodium hydride (55% in mineral oil, 71 mg) was added in one portion. The mixture was stirred until gas evolution stopped (approx. 20 minutes) and then a solution of 2-trifluoromethyl-5-fluorobenzyl bromide (307 mg) in DMF (2 mL) was added over 5 minutes. Stirring was continued for 1 hour and then the reaction mixture was poured into brine. The aqueous solution was extracted with ethyl acetate and the organic layer was separated and washed with brine. The combined organic extracts were dried over Na2SO4 and evaporated. Residual DMF was removed by co-evaporation with toluene. The crude material was purified by flash chromatography using a gradient of 20 to 50% ethyl acetate in heptane as an eluent. Fractions containing the desired product were combined and evaporated to give 3-cyclopropyl-1-(5-fluoro-2-trifluoromethyl-benzyl)-4-methyl-1,3-dihydro-imidazol-2-one as a colorless oil (201 mg). MS (ESI): 315.1 (MH+).

Workup

  1. custom(approx. 20 minutes)
  2. stirringStirring
  3. extractionThe aqueous solution was extracted with ethyl acetate
  4. customthe organic layer was separated
  5. washwashed with brine
  6. dry with materialThe combined organic extracts were dried over Na2SO4
  7. customevaporated
  8. customResidual DMF was removed by co-evaporation with toluene
  9. customThe crude material was purified by flash chromatography
  10. additionFractions containing the desired product
  11. customevaporated

Sources & evidence

ORD record
ord-da4ead1c4bcb490babe7c427c5025ed7
Source dataset
uspto-grants-2012_03
Patent number
US08129423B2

Reaction notes

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