Acetic Anhydride → HCID 57782258, compound

HRID 1670849Notes

Reaction equation

HRID 1670849 reaction equation
[Li]CCCC.CC(OC(C)=O)=O.[CH2:13]([N:15]1[C:19]([C:20](=[O:22])[CH3:21])=[CH:18][N:17]=[C:16]1[O:23][C:24]1[CH:29]=[CH:28][C:27]([CH3:30])=[CH:26][CH:25]=1)[CH3:14].C(N1C=CN=C1OC1C=CC(C)=CC=1)C.[BH4-].[Na+]>C1COCC1.C(=O)(O)[O-].[Na+].CO>[CH2:13]([N:15]1[C:19]([CH:20]([OH:22])[CH3:21])=[CH:18][N:17]=[C:16]1[O:23][C:24]1[CH:25]=[CH:26][C:27]([CH3:30])=[CH:28][CH:29]=1)[CH3:14]

Participants

9

Reactant 5

HCID 7918Acetic AnhydrideHCID 4311764Sodium borohydrideHCID 57782331HCID 57782331, compoundHCID 67347287HCID 67347287, compoundHCID 178418339Butyllithium

Product 1

HCID 57782258HCID 57782258, compound

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolventHCID 516892Sodium BicarbonateSolvent

Conditions

Temperature
-100 °C

Procedure

To a solution of the compound obtained in Example 1-(2) (2.493 g) in THF (123 ml), n-BuLi (4.8 ml, 2.59 N in hexane) was added dropwise at −78° C. under an argon atmosphere and stirred at the same temperature for 3.5 hours. The reaction mixture was cooled to −100° C., mixed with Ac2O (2.3 ml), warmed to −65° C. over 50 minutes, diluted with saturated aqueous sodium bicarbonate, and extracted with AcOEt. After washing with brine, the organic layer was dried over MgSO4, filtered and then evaporated to remove the solvent. The resulting crude product was purified by column chromatography (NH-type silica gel, AcOEt/hexane=10% to 30%) to give a mixture of 1-(3-ethyl-2(4-methylphenoxy)-3H-imidazol-4-yl)-ethanone and 1-ethyl-2(4-methylphenoxy)-1H-imidazole (1.509 g, colorless oil). To a solution of the resulting compounds (1.508 g) in MeOH (13 ml), NaBH4 (243 mg) was added at 0° C. and stirred at the same temperature for 15 minutes and then at room temperature for 15 minutes. The reaction mixture was concentrated, diluted with water, and extracted with AcOEt. After washing with brine, the organic layer was dried over MgSO4, filtered and then evaporated to remove the solvent. The resulting crude product was purified by column chromatography (NH-type silica gel, AcOEt/hexane=20% to 99%) to give the titled compound (1.131 g, colorless oil).

Workup

  1. temperaturewarmed to −65° C. over 50 minutes
  2. extractionextracted with AcOEt
  3. washAfter washing with brine
  4. dry with materialthe organic layer was dried over MgSO4
  5. filtrationfiltered
  6. customevaporated
  7. customto remove the solvent
  8. customThe resulting crude product was purified by column chromatography (NH-type silica gel, AcOEt/hexane=10% to 30%)
  9. customto give
  10. stirringstirred at the same temperature for 15 minutes
  11. waitat room temperature for 15 minutes
  12. concentrationThe reaction mixture was concentrated
  13. additiondiluted with water
  14. extractionextracted with AcOEt
  15. washAfter washing with brine
  16. dry with materialthe organic layer was dried over MgSO4
  17. filtrationfiltered
  18. customevaporated
  19. customto remove the solvent
  20. customThe resulting crude product was purified by column chromatography (NH-type silica gel, AcOEt/hexane=20% to 99%)

Sources & evidence

ORD record
ord-1116a6154e4e478cafdc7ae8a996e0cb
Source dataset
uspto-grants-2011_08
Patent number
US07994204B2

Reaction notes

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