Benzimidazole → 1-[(4-fluorophenyl)methyl]-1H-1,3-benzodiazole

HRID 1647044Notes

Reaction equation

HRID 1647044 reaction equation
[N:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[NH:3][CH:2]=1.CN(C=O)C.[H-].[Na+].[F:17][C:18]1[CH:25]=[CH:24][C:21]([CH2:22]Cl)=[CH:20][CH:19]=1>C1(C)C=CC=CC=1.C(OCC)(=O)C.O>[F:17][C:18]1[CH:25]=[CH:24][C:21]([CH2:22][N:1]2[C:5]3[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=3[N:3]=[CH:2]2)=[CH:20][CH:19]=1

Participants

8

Reactant 4

HCID 5798BenzimidazoleHCID 6228DimethylformamideHCID 96024-Fluorobenzyl chlorideHCID 24758Sodium hydride

Product 1

HCID 7555721-[(4-fluorophenyl)methyl]-1H-1,3-benzodiazole

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a stirred, room temperature, solution of benzimidazole (11.8 g, 1.00×10-1 mole) and dry DMF (100 ml) was added portion-wise sodium hydride (4.4 g, 1.1×10-1 mole, 60% oil dispersion). After ca. 30 minutes, 4-fluorobenzyl chloride (14.6 g, 1.01×10-1 mole) was added. The reaction was stirred at room temperature for ca. 17 hours and was then poured into a separatory funnel containing water and a 2:1 mixture of ethyl acetate:toluene. The two phases were mixed and the aqueous layer was separated. The organic layer was washed two times with H20 and once with saturated aqueous NaCl before being dried over anhydrous Na2SO4. The drying agent was removed by filtration and the filtrate was evaporated at reduced pressure leaving an oil which was purified by flash chromatography (20% acetone/ethyl acetate). The resulting oil was kugelrohr distilled (230-245° C./0.3 mm) affording 1-[(4-fluorophenyl)methyl]-1H-benzimidazole as an oil which solidified giving a colorless solid: 17.4 g (77%), m.p. 60-62° C.

Workup

  1. additionwas then poured into a separatory funnel
  2. additionThe two phases were mixed
  3. customthe aqueous layer was separated
  4. washThe organic layer was washed two times with H20
  5. dry with materialonce with saturated aqueous NaCl before being dried over anhydrous Na2SO4
  6. customThe drying agent was removed by filtration
  7. customthe filtrate was evaporated at reduced pressure
  8. customleaving an oil which
  9. customwas purified by flash chromatography (20% acetone/ethyl acetate)
  10. distillationdistilled (230-245° C./0.3 mm)

Sources & evidence

ORD record
ord-641c41f19eff4965859ab1c1d7c29650
Source dataset
uspto-grants-1993_01
Patent number
US05182399

Reaction notes

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