Azobisisobutyronitrile → Ethyl [4-chloro-7-(1-ethylpropyl)-2-oxo-2,3-dihydro-1H-benzimidazol-1-yl]acetate

HRID 1398744Notes

Reaction equation

HRID 1398744 reaction equation
[CH2:1]([CH:3]([C:6]1[C:11]2[N:12]([CH2:16][C:17]([O:19][CH2:20][CH3:21])=[O:18])[C:13](=[O:15])[NH:14][C:10]=2[CH:9]=[CH:8][CH:7]=1)[CH2:4][CH3:5])[CH3:2].N(C(C)(C)C#N)=NC(C)(C)C#N.[Cl:34]N1C(=O)CCC1=O>ClC1C=CC=CC=1>[Cl:34][C:9]1[C:10]2[NH:14][C:13](=[O:15])[N:12]([CH2:16][C:17]([O:19][CH2:20][CH3:21])=[O:18])[C:11]=2[C:6]([CH:3]([CH2:4][CH3:5])[CH2:1][CH3:2])=[CH:7][CH:8]=1

Participants

5

Reactant 3

HCID 6547AzobisisobutyronitrileHCID 31398ChlorosuccinimideHCID 86632858Ethyl [7-(1-ethylpropyl)-2-oxo-2,3-dihydro-1H-benzimidazol-1-yl]acetate

Product 1

HCID 86632859Ethyl [4-chloro-7-(1-ethylpropyl)-2-oxo-2,3-dihydro-1H-benzimidazol-1-yl]acetateYield 63.2%

Reagents, catalysts & solvents 1

HCID 7964ChlorobenzeneSolvent

Conditions

Temperature
70 °C

Procedure

To a solution of ethyl [7-(1-ethylpropyl)-2-oxo-2,3-dihydro-1H-benzimidazol-1-yl]acetate (3.91 g, 13.5 mmol) and 2,2′-azobisisobutyronitrile (222 mg, 1.35 mmol) in chlorobenzene (40 mL) was added portionwise N-chlorosuccinimide (1.80 g, 13.5 mmol) at 65° C., and the mixture was stirred at 70° C. for 2 days. After cooling, the reaction mixture was washed with saturated aqueous sodium hydrogen carbonate. The aqueous layer was separated and extracted with ethyl acetate. The organic layer was washed with brine, dried over anhydrous sodium sulfate and concentrated in vacuo. The residue was purified by silica gel column chromatography eluting with a 15-50% ethyl acetate/n-hexane gradient mixture, and the fractions containing the title compound were concentrated in vacuo. The mixture was suspended in diisopropyl ether, and the suspension was stirred at 60° C. for 2 hr. After cooling, the resulting solid was collected by filtration and washed with n-hexane to give the title compound (2.77 g, 8.53 mmol, 63%) as a colorless solid.

Workup

  1. temperatureAfter cooling
  2. washthe reaction mixture was washed with saturated aqueous sodium hydrogen carbonate
  3. customThe aqueous layer was separated
  4. extractionextracted with ethyl acetate
  5. washThe organic layer was washed with brine
  6. dry with materialdried over anhydrous sodium sulfate
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by silica gel column chromatography
  9. washeluting with a 15-50% ethyl acetate/n-hexane gradient mixture
  10. additionthe fractions containing the title compound
  11. concentrationwere concentrated in vacuo
  12. stirringthe suspension was stirred at 60° C. for 2 hr
  13. temperatureAfter cooling
  14. filtrationthe resulting solid was collected by filtration
  15. washwashed with n-hexane

Sources & evidence

ORD record
ord-8e7ae5947c1048ac9dd8c88f359fc793
Source dataset
uspto-grants-2014_12
Patent number
US08901141B2

Reaction notes

Loading…