Sodium hydride → Methyl 1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazole-4-carboxylate

HRID 528989Notes

Reaction equation

HRID 528989 reaction equation
[H-].[Na+].[NH:3]1[CH:7]=[C:6]([C:8]([O:10][CH3:11])=[O:9])[N:5]=[CH:4]1.Cl[CH2:13][O:14][CH2:15][CH2:16][Si:17]([CH3:20])([CH3:19])[CH3:18]>CN(C=O)C>[CH3:18][Si:17]([CH3:20])([CH3:19])[CH2:16][CH2:15][O:14][CH2:13][N:3]1[CH:7]=[C:6]([C:8]([O:10][CH3:11])=[O:9])[N:5]=[CH:4]1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 27242712-Chloromethyl 2-(trimethylsilyl)ethyl etherHCID 178418785HCID 178418785, compound

Product 1

HCID 22954042Methyl 1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazole-4-carboxylateYield 73.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

To a stirred suspension of sodium hydride (572 mg, 23.8 mmol, 94%) in dry DMF (50 mL) at 0° C. was added methyl 1H-imidazole-4-carboxylate (3.0 g, 23.8 mmol) in DMF (90 mL) and was allowed to warm up to room temperature over 30 min. The reaction mixture was cooled to 0° C. and was treated dropwise with (2-(chloromethoxy)ethyl)trimethylsilane (Aldrich, 4.77 g, 28.6 mmol). The cold bath was removed and the mixture was stirred for 16 h. The reaction mixture was quenched by the addition of ice-flakes and then by water, and extracted with EtOAc (3×). The combined organic layers were washed with brine, dried over Na2SO4 and concentrated in vacuo to give crude product. The crude material was purified by flash chromatography (gradient from 2 to 5% MeOH/CH2Cl2) to provide the title compound (4.46 g, 73%). 1H NMR (CDCl3) δ 7.72 (s, 1H), 7.61 (s, 1H), 5.29 (s, 2H), 3.90 (s, 3H), 3.49 (t, J=8.0 Hz, 2H), 0.90 (t, J=8.0 Hz, 2H), 0.01 (s, 9H); MS(ESI+) m/z 257.2 (M+H)+.

Workup

  1. temperatureThe reaction mixture was cooled to 0° C.
  2. customThe cold bath was removed
  3. customThe reaction mixture was quenched by the addition of ice-flakes
  4. extractionby water, and extracted with EtOAc (3×)
  5. washThe combined organic layers were washed with brine
  6. dry with materialdried over Na2SO4
  7. concentrationconcentrated in vacuo
  8. customto give crude product
  9. customThe crude material was purified by flash chromatography (gradient from 2 to 5% MeOH/CH2Cl2)

Sources & evidence

ORD record
ord-d714189769174fac8d2fb400d81e0f77
Source dataset
uspto-grants-2016_05
Patent number
US09346795B2

Reaction notes

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