4-Fluoroaniline → Ethyl 1-(4-fluorophenyl)imidazole-5-carboxylate

HRID 2368477Notes

Reaction equation

HRID 2368477 reaction equation
[F:1][C:2]1[CH:8]=[CH:7][C:5]([NH2:6])=[CH:4][CH:3]=1.[C:9]([O:13][CH2:14][CH3:15])(=[O:12])[CH:10]=O.C1(C)C(S([CH2:25][N+:26]#[C-:27])(=O)=O)=CC=CC=1.C(=O)([O-])[O-].[K+].[K+]>C1(C)C=CC=CC=1.[Cl-].[Na+].O.C(O)C>[F:1][C:2]1[CH:8]=[CH:7][C:5]([N:6]2[C:10]([C:9]([O:13][CH2:14][CH3:15])=[O:12])=[CH:27][N:26]=[CH:25]2)=[CH:4][CH:3]=1

Participants

8

Reactant 4

HCID 97314-FluoroanilineHCID 11430Potassium CarbonateHCID 70211Ethyl oxoacetateHCID 53627694Toluenesulfonylmethyl isocyanide

Product 1

HCID 55563221Ethyl 1-(4-fluorophenyl)imidazole-5-carboxylate

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 1140TolueneSolventHCID 57417360Sodium chloride; waterSolvent

Procedure

A mixture of 4-fluoroaniline (2.8 g, 25.0 mmol), ethyl glyoxylate (50% solution, 5.14 g, 25.0 mmol), in toluene (30 mL) was refluxed overnight. The reaction was filtered and concentrated in vacuo. To the residue was added ethanol (30 mL), toluenesulfonylmethyl isocyanide (TOSMIC) (4.9 g, 25 mmol), and potassium carbonate (6.9 g, 50.0 mmol) and the mixture was stirred at room temperature for 1 h. Brine was added and mixture was extracted with ethyl acetate. The combined organic layers were dried over sodium sulfate, filtered and concentrated in vacuo. The residue was purified by flash column chromatography on silica gel (0-60% EtOAc in hexanes) to afford ethyl 1-(4-fluorophenyl)-1H-imidazole-5-carboxylate (14a).

Workup

  1. filtrationThe reaction was filtered
  2. concentrationconcentrated in vacuo
  3. extractionmixture was extracted with ethyl acetate
  4. dry with materialThe combined organic layers were dried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by flash column chromatography on silica gel (0-60% EtOAc in hexanes)

Sources & evidence

ORD record
ord-33e79decc8bd413a930d6697c18a1363
Source dataset
uspto-grants-2014_04
Patent number
US08703776B2

Reaction notes

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