Sodium hydride → HCID 86750056, compound

HRID 1080746Notes

Reaction equation

HRID 1080746 reaction equation
[CH2:1]([O:3][C:4](=[O:11])[CH2:5][C:6]1[N:7]=[CH:8][NH:9][CH:10]=1)[CH3:2].[H-].[Na+].[CH3:14][Si:15]([CH3:22])([CH3:21])[CH2:16][CH2:17][O:18][CH2:19]Cl>O1CCCC1.C(OCC)(=O)C>[CH3:14][Si:15]([CH3:22])([CH3:21])[CH2:16][CH2:17][O:18][CH2:19][N:9]1[CH:10]=[C:6]([CH2:5][C:4]([O:3][CH2:1][CH3:2])=[O:11])[N:7]=[CH:8]1

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 27242712-Chloromethyl 2-(trimethylsilyl)ethyl etherHCID 178470744HCID 178470744, compound

Product 1

HCID 86750056HCID 86750056, compoundYield 48.5%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 383 gm (2.48 mmol) of 1H-imidazole-4-acetic acid ethyl ester (prepared according to the procedure of Bashkin et al; J. Org. Chem., 1990, 55, 5125-5132.) in 5 mL of dry tetrahydrofuran under a nitrogen atmosphere was added 109 mg (2.73 mmol) of 60% sodium hydride/oil dispersion. The resulting mixture was stirred for 30 minutes at which time was added dropwise by syringe 0.53 mL (3.0 mmol) of 2-trimethylsilylethoxymethyl chloride. The reaction mixture was stirred for 4 hours at room temperature then diluted with 150 mL of ethyl acetate. The solution was washed with saturated aqueous sodium bicarbonate, dried over magnesium sulfate, filtered and the solvent removed under vacuum. The resulting material was purified by column chromatography on silica gel, eluting with chloroform/10% concentrated ammonium hydroxide in methanol (96:4), to afford 342 mg (48%) of the products in a 1.5:1 ratio of N-1:N-3 imidazole regioisomers as a colorless oil. FAB-MS: calculated for C13H24N2O3Si 284; found 285 (M+H, 100%). 1H NMR (200 MHz, CDCl3): 0.00 (s, 18H), 0.90 (m, 4H), 1.25 (t, 7 Hz, 6H), 3.45 (m, 4H), 3.65 (s, 2H), 3.70 (s, 2H), 4.15 (m, 4H), 5.20 (s, 2H), 5.35 (s, 2H), 7.00 (s, 1H), 7.02 (s, 1H), 7.65 (s, 1H), 7.97 (s, 1H).

Workup

  1. stirringThe reaction mixture was stirred for 4 hours at room temperature
  2. washThe solution was washed with saturated aqueous sodium bicarbonate
  3. dry with materialdried over magnesium sulfate
  4. filtrationfiltered
  5. customthe solvent removed under vacuum
  6. customThe resulting material was purified by column chromatography on silica gel
  7. washeluting with chloroform/10% concentrated ammonium hydroxide in methanol (96:4)

Sources & evidence

ORD record
ord-18931681826942cfa78c0206340f46e8
Source dataset
uspto-grants-1996_12
Patent number
US05583130

Reaction notes

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