Reaction #329570

Reaction equation

ammonium chloride

n-butyl lithium

4-(tert-Butyldiphenylsilyloxymethyl)-5-methyl-1-(2-trimethylsilylethoxymethyl)-1H-imidazole

N-methoxy-N-methylacetamide

→

title compound

1-[4-(tert-Butyldiphenylsilyloxymethyl)-5-methyl-1-(2-trimethylsilylethoxymethyl)-1H-imidazol-2-yl]ethanone

Solvents

THF

Conditions

Workup

1. 1
   workup.STIRRINGby stirring at the same temperature for 30 minutes
2. 2
   workup.STIRRINGstirring
3. 3
   Temperaturewas raised to room temperature
4. 4
   Otherto terminate
5. 5
   Otherthe reaction
6. 6
   Extractionfollowed by extraction with ethyl acetate
7. 7
   ExtractionThe combined extract
8. 8
   Washwas washed with saturated brine
9. 9
   Dryingdried over anhydrous sodium sulfate
10. 10
    workup.DISTILLATIONsubsequently the solvent was distilled off under reduced pressure
11. 11
    OtherThe resulting residue was purified by flash chromatography (ethyl acetate/hexane=0%→50%)

Procedure

4-(tert-Butyldiphenylsilyloxymethyl)-5-methyl-1-(2-trimethylsilylethoxymethyl)-1H-imidazole (24.6 g) was dissolved in THF (300 mL), and cooled to −78° C. while stirring under an argon atmosphere. To the present solution was added dropwise n-butyl lithium (2.66 M hexane solution, 28.9 mL) slowly using a syringe, followed by stirring at the same temperature for 30 minutes. Then, N-methoxy-N-methylacetamide (10.5 mL) was added using a syringe, and stirring was continued for 2 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=0%→50%) using silica gel column (product name: Hi-Flash Column 5 L, manufactured by Yamazen Corporation) to afford the title compound (11.7 g).

Source