Ammonium Chloride → 1-[1-Ethoxymethyl-4-(triethylsilyloxymethyl)-1H-imidazol-2-yl]ethanone

HRID 242371

Reaction equation

HRID 242371 reaction equation
[CH2:1]([O:3][CH2:4][N:5]1[CH:9]=[C:8]([CH2:10][O:11][Si:12]([CH2:17][CH3:18])([CH2:15][CH3:16])[CH2:13][CH3:14])[N:7]=[CH:6]1)[CH3:2].C([Li])CCC.CON(C)[C:27](=[O:29])[CH3:28].[Cl-].[NH4+]>C1COCC1>[CH2:1]([O:3][CH2:4][N:5]1[CH:9]=[C:8]([CH2:10][O:11][Si:12]([CH2:13][CH3:14])([CH2:17][CH3:18])[CH2:15][CH3:16])[N:7]=[C:6]1[C:27](=[O:29])[CH3:28])[CH3:2]

Participants

6

Reactant 4

HCID 25517Ammonium ChlorideHCID 537505N-Methoxy-N-methylacetamideHCID 710871261-Ethoxymethyl-4-(triethylsilyloxymethyl)-1H-imidazoleHCID 178418339Butyllithium

Product 1

HCID 710871971-[1-Ethoxymethyl-4-(triethylsilyloxymethyl)-1H-imidazol-2-yl]ethanone

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

The compound (665 mg) obtained in (3) was dissolved in THF (20 mL), and cooled to −78° C. while stirring under an argon atmosphere. To the present solution was added dropwise n-butyl lithium (2.69 M hexane solution, 1.50 mL) slowly using a syringe, followed by stirring at the same temperature for 30 minutes. Then, N-methoxy-N-methylacetamide (0.50 mL) was added using a syringe, and stirring was continued for 17 hours while the temperature was raised to room temperature. A saturated aqueous ammonium chloride solution was added to the reaction solution to terminate the reaction, followed by extraction with ethyl acetate. The combined extract was washed with saturated brine, dried over anhydrous sodium sulfate, and subsequently the solvent was distilled off under reduced pressure. The resulting residue was purified by flash chromatography (ethyl acetate/hexane=5%→30%) using silica gel column (product name: SNAP Cartridge KP-Sil 50 g, manufactured by Biotage, Ltd.) to afford the title compound (520 mg).

Workup

  1. stirringby stirring at the same temperature for 30 minutes
  2. stirringstirring
  3. temperaturewas raised to room temperature
  4. customto terminate
  5. customthe reaction
  6. extractionfollowed by extraction with ethyl acetate
  7. extractionThe combined extract
  8. washwas washed with saturated brine
  9. dry with materialdried over anhydrous sodium sulfate
  10. distillationsubsequently the solvent was distilled off under reduced pressure
  11. customThe resulting residue was purified by flash chromatography (ethyl acetate/hexane=5%→30%)

Sources & evidence

ORD record
ord-73cc6da7e7a2401c83c4203824121362
Source dataset
uspto-grants-2014_02
Patent number
US08653126B2

Linked notes

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