Acetonitrile → 5-(tert-butyldiphenylsilyloxymethyl)-4-methyl-1-(2-trimethylsilylethoxymethyl)-1H-imidazole

HRID 242384Notes

Reaction equation

HRID 242384 reaction equation
[Si:1]([O:18][CH2:19][C:20]1[N:21]=[CH:22][N:23]([CH2:25]C=C)[CH:24]=1)([C:14]([CH3:17])([CH3:16])[CH3:15])([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:28][Si:29]([CH3:36])([CH3:35])[CH2:30][CH2:31][O:32][CH2:33]Cl.[C:37](#N)C>>[Si:1]([O:18][CH2:19][C:20]1[N:21]=[CH:22][N:23]([CH2:25][O:32][CH2:31][CH2:30][Si:29]([CH3:36])([CH3:35])[CH3:28])[C:24]=1[CH3:37])([C:14]([CH3:16])([CH3:17])[CH3:15])([C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1)[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1.[Si:1]([O:18][CH2:19][C:20]1[N:21]([CH2:33][O:32][CH2:31][CH2:30][Si:29]([CH3:36])([CH3:35])[CH3:28])[CH:22]=[N:23][C:24]=1[CH3:37])([C:14]([CH3:16])([CH3:17])[CH3:15])([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 6342AcetonitrileHCID 27242712-Chloromethyl 2-(trimethylsilyl)ethyl ether2×HCID 892621944-(tert-Butyldiphenylsilyloxymethyl)-1-(2-propenyl)-1H-imidazole

Product 2

HCID 710871795-(tert-butyldiphenylsilyloxymethyl)-4-methyl-1-(2-trimethylsilylethoxymethyl)-1H-imidazoleHCID 710874044-(tert-butyldiphenylsilyloxymethyl)-5-methyl-1-(2-trimethylsilylethoxymethyl)-1H-imidazole

Procedure

The mixture (35.4 g) obtained in (1) was dissolved in acetonitrile (500 mL), followed by addition of TEA (37.8 mL) and then 2-trimethylsilylethoxymethyl chloride (hereinafter, also referred to as SEMCl) (21.4 mL) while stirring under ice cooling, followed by stirring at 70° C. for 12 hours. The reaction mixture was allowed to cool to room temperature, and the solvent was distilled off under reduced pressure. The residue was diluted with ethyl acetate, subsequently washed with saturated brine, and dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure, and the resulting residue was purified by flash chromatography (ethyl acetate/hexane=15%→50%) using silica gel column (product name: cartridge 65i, manufactured by Biotage, Ltd.) to afford 4-(tert-butyldiphenylsilyloxymethyl)-5-methyl-1-(2-trimethylsilylethoxymethyl)-1H-imidazole (17.9 g) as a low polar component, and 5-(tert-butyldiphenylsilyloxymethyl)-4-methyl-1-(2-trimethylsilylethoxymethyl)-1H-imidazole (9.42 g) as a high polar component.

Workup

  1. stirringby stirring at 70° C. for 12 hours
  2. distillationthe solvent was distilled off under reduced pressure
  3. additionThe residue was diluted with ethyl acetate
  4. washsubsequently washed with saturated brine
  5. dry with materialdried over anhydrous sodium sulfate
  6. distillationThe solvent was distilled off under reduced pressure
  7. customthe resulting residue was purified by flash chromatography (ethyl acetate/hexane=15%→50%)

Sources & evidence

ORD record
ord-bb463b23b33f4b8a8e5b415397b43c1e
Source dataset
uspto-grants-2014_02
Patent number
US08653126B2

Reaction notes

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