Imidazole → 4-(2-(1H-imidazol-1-yl)ethoxy)benzamide

HRID 980140Notes

Reaction equation

HRID 980140 reaction equation
[H-].[Na+].[NH:3]1[CH:7]=[CH:6][N:5]=[CH:4]1.Cl[CH2:9][CH2:10][O:11][C:12]1[CH:20]=[CH:19][C:15]([C:16]([NH2:18])=[O:17])=[CH:14][CH:13]=1>CN(C)C=O>[C:16]([C:15]1[CH:19]=[CH:20][C:12]([O:11][CH2:10][CH2:9][N:3]2[CH:7]=[CH:6][N:5]=[CH:4]2)=[CH:13][CH:14]=1)(=[O:17])[NH2:18]

Participants

5

Reactant 3

HCID 795ImidazoleHCID 24758Sodium hydrideHCID 135691714-(2-Chloroethoxy)benzamide

Product 1

HCID 135691774-(2-(1H-imidazol-1-yl)ethoxy)benzamideYield 50.8%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
100 °C

Procedure

Sodium hydride (14.4 g, 50% suspension in mineral oil) was added cautiously to a stirred and cooled solution of imidazole (20.4 g) in dry N,N-dimethylformamide (100 ml). After the initial vigorous reaction had subsided the mixture was heated to 100° C. for 10 minutes and then stirred at room temperature for a further 1 hour. A solution of 4-(2-chloroethoxy)benzamide (60.0 g) in the minimum volume of N,N-dimethylformamide was added and the mixture was heated at 100° C. for 5.5 hours. The solvent was evaporated and the residue was poured into water. The mixture was extracted several times with chloroform and the combined chloroform extracts were dried (MgSO4) and evaporated to give a mixture of oil and solid. The mixture was triturated with ether and the solid was collected and crystallised from a mixture of methanol and ethyl acetate to give 1-[2-(4-carbamoyl phenoxy)ethyl]imidazole (35.2 g), m.p. 148°-149° C. Found: C, 62.25; H, 5.61; N, 18.54. C12H13N3O2 requires C, 62.32; H, 5.67; N, 18.17%.

Workup

  1. customAfter the initial vigorous reaction
  2. stirringstirred at room temperature for a further 1 hour
  3. temperaturethe mixture was heated at 100° C. for 5.5 hours
  4. customThe solvent was evaporated
  5. additionthe residue was poured into water
  6. extractionThe mixture was extracted several times with chloroform
  7. dry with materialthe combined chloroform extracts were dried (MgSO4)
  8. customevaporated
  9. customto give
  10. additiona mixture of oil and solid
  11. customThe mixture was triturated with ether
  12. customthe solid was collected
  13. customcrystallised from a mixture of methanol and ethyl acetate

Sources & evidence

ORD record
ord-6562182901ca4904af4a1c1351837531
Source dataset
uspto-grants-1987_01
Patent number
US04636500

Reaction notes

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