Benzimidazole → 1-benzyloxymethyl-1H-benzimidazole

HRID 2104950Notes

Reaction equation

HRID 2104950 reaction equation
[N:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[NH:3][CH:2]=1.[H-].[Na+].[CH2:12](Cl)[O:13][CH2:14][C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1>CN(C=O)C.CCOC(C)=O>[CH2:14]([O:13][CH2:12][N:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[CH:2]1)[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1

Participants

6

Reactant 3

HCID 5798BenzimidazoleHCID 24758Sodium hydrideHCID 137983Benzyl chloromethyl ether

Product 1

HCID 113223751-benzyloxymethyl-1H-benzimidazoleYield 44.9%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of benzimidazole (500 mg, 4.23 mmol) in 10 mL DMF at 0° C., was added NaH (60%, 169 mg, 4.23 mmol). The mixture was stirred for 20 min, then BOM-Cl (802 μL, 4.65 mmol) was added. The mixture was stirred at rt for 4 h, then was diluted with EtOAc. The organic phase was washed with H2O (3×) and brine, dried (Na2SO4), filtered through 1″ SiO2 (eluting with EtOAc). The crude product was purified by flash chromatography (30 to 100% EtOAc/hexanes gradient) to afford 453 mg of Intermediate 10.1 as a white crystalline solid.

Workup

  1. stirringThe mixture was stirred at rt for 4 h
  2. washThe organic phase was washed with H2O (3×) and brine
  3. dry with materialdried (Na2SO4)
  4. filtrationfiltered through 1″ SiO2 (eluting with EtOAc)
  5. customThe crude product was purified by flash chromatography (30 to 100% EtOAc/hexanes gradient)

Sources & evidence

ORD record
ord-6a113195cba24441b53b5251ada9945f
Source dataset
uspto-grants-2009_08
Patent number
US07576098B2

Reaction notes

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