Hydrogen Peroxide → HCID 178513759, compound

HRID 2227730Notes

Reaction equation

HRID 2227730 reaction equation
[F:1][C:2]1[CH:21]=[CH:20][C:5]([O:6][C:7]2[CH:12]=[CH:11][C:10]([C:13]3[NH:14][CH:15]=[C:16]([C:18]#[N:19])[N:17]=3)=[CH:9][CH:8]=2)=[CH:4][CH:3]=1.[OH-].[K+].OO.O.CC[O:29]C(C)=O>CCO.O>[F:1][C:2]1[CH:21]=[CH:20][C:5]([O:6][C:7]2[CH:8]=[CH:9][C:10]([C:13]3[NH:14][CH:15]=[C:16]([C:18]([NH2:19])=[O:29])[N:17]=3)=[CH:11][CH:12]=2)=[CH:4][CH:3]=1

Participants

7

Reactant 4

HCID 784Hydrogen PeroxideHCID 14797Potassium HydroxideHCID 22728543Water ethylacetateHCID 178510372HCID 178510372, compound

Product 1

HCID 178513759HCID 178513759, compound

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 962WaterSolvent

Procedure

To a solution of 0.56 g (6.83 mmol) of sodium acetate in 10 mL of water was added 1.29 g (4.78 mmol) of 1,1-dibromo-3,3,3-trifluoroacetone. The resulting solution was warmed for 30 minutes and then cooled in an ice/water bath. A solution of 4-(fluorophenoxy)benzaldehyde (789 mg, 3.65 mmol) in MeOH was added, followed by 10 mL of a concentrated aqueous NH4OH solution. Additional MeOH was added until a homogenous solution formed. After stirring at room temperature overnight, the reaction was diluted with water. The precipitate that formed was collected, washed with water and dried. Column chromatography (gradient from 8/2 to 2/3 hexane/EtOAc) afforded 0.6 g of a solid. A mixture of 0.5 g of the solid and 80 mL of a concentrated aqueous NH4OH solution was diluted with MeOH until a solution formed. The reaction was heated in a sealed tube for 1.5 days. After cooling to room temperature, the mixture was added to a water/EtOAc mixture. The aqueous layer was extracted with EtOAc and the combined organic layers were washed with water, dried (Na2SO4), filtered and concentrated to dryness. Column chromatography (1:1 hexane/EtOAc) gave 2-[4-(4-fluorophenoxy)phenyl]-1H-imidazole-4-carbonitrile as a solid. 1H NMR (DMSO-d6): δ13.37 (br s, 1H), 8.23 (s, 1H), 7.95 (d, 2H, J=8.7 Hz), 7.27 (t, 2H, J=8.9 Hz), 7.15 (dd, 2H, J=9.3, 4.5 Hz), 7.08 (d, 2H, J=8.7 Hz). To a solution of the nitrile in EtOH was added 1 g of KOH dissolved in 5 mL of water and 1.5 mL of a 30% aq. H2O2 solution. After heating at reflux for 3 hours, the reaction was added to water/EtOAc. The organic layer was dried (Na2SO4), filtered and evaporated in vacuo. The residue was subjected to flash chromatography (100% EtOAc) affording the title compound as a white solid, TLC Rf 0.34 (5% MeOH/EtOAc). 1H NMR (CDCl3): δ12.90 (br s, 1H), 8.08 (br s, 1H), 7.97 (d, 2H, J=9.0 Hz), 7.70 (s, 1H), 7.63 (br s, 1H), 7.26 (t, 2H, J=8.7 Hz), 7.15-7.10 (m, 2H), 7.07 (d, 2H, J=8.7 Hz).

Workup

  1. temperatureAfter heating
  2. temperatureat reflux for 3 hours
  3. dry with materialThe organic layer was dried (Na2SO4)
  4. filtrationfiltered
  5. customevaporated in vacuo

Sources & evidence

ORD record
ord-92e1b00f89dc494dbacb0ebccfba19c6
Source dataset
uspto-grants-2002_07
Patent number
US06414011B1

Reaction notes

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