Dimethylformamide → 3-Butyl-5-dimethoxymethyl-2-phenyl-3H-imidazole-4-carbaldehyde

HRID 457396Notes

Reaction equation

HRID 457396 reaction equation
[CH2:1]([N:5]1[CH:9]=[C:8]([CH:10]([O:13][CH3:14])[O:11][CH3:12])[N:7]=[C:6]1[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)[CH2:2][CH2:3][CH3:4].[Li]CCCC.CN([CH:29]=[O:30])C.[Cl-].[NH4+]>C1COCC1.C(OCC)(=O)C>[CH2:1]([N:5]1[C:9]([CH:29]=[O:30])=[C:8]([CH:10]([O:13][CH3:14])[O:11][CH3:12])[N:7]=[C:6]1[C:15]1[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=1)[CH2:2][CH2:3][CH3:4]

Participants

7

Reactant 4

HCID 6228DimethylformamideHCID 25517Ammonium ChlorideHCID 184377881-Butyl-4-dimethoxymethyl-2-phenyl-1H-imidazoleHCID 178418339Butyllithium

Product 1

HCID 184378613-Butyl-5-dimethoxymethyl-2-phenyl-3H-imidazole-4-carbaldehyde

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 1-butyl-4-dimethoxymethyl-2-phenyl-1H-imidazole 209 (2.74 g, 10 mmol) in anhydrous THF under nitrogen at −78° C., n-BuLi (1.6 M in hexane, 7.5 ml, 12 mmol) is added dropwise and the mixture is continued stirring at this temperature for 30 min. After anhydrous DMF (4 mL) is added, the mixture is stirred at room temperature for 16 h. Saturated ammonium chloride and ethyl acetate were added at 0° C. and the the organic phase is separated. The aqueous phase is extracted with ethyl acetate and the combined organic phase is washed with brine, dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue is purified by column chromatography to yield the desired product as a white solid. Yield: 1.94 g; LC-MS (MH+): 303. 1H NMR (300 MHz, CDCl3) δ 10.18 (s, 1H), 7.60–7.56 (m, 2H), 7.51–7.46 (m, 3H), 5.63 (s, 1H), 4.32 (t, J=6.3 Hz, 2H), 3.47 (s, 6H), 1.73–1.63 (m, 2H), 1.28–1.16 (m, 2H), 0.82 (t, J=7.2 Hz, 3H).

Workup

  1. stirringthe mixture is stirred at room temperature for 16 h
  2. customthe the organic phase is separated
  3. extractionThe aqueous phase is extracted with ethyl acetate
  4. washthe combined organic phase is washed with brine
  5. dry with materialdried over anhydrous sodium sulfate
  6. concentrationconcentrated under reduced pressure
  7. customThe residue is purified by column chromatography

Sources & evidence

ORD record
ord-20253f7cec2e4097b1c17e0469bbc2ab
Source dataset
uspto-grants-2007_03
Patent number
US07186734B2

Reaction notes

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