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

HRID 1628384Notes

Reaction equation

HRID 1628384 reaction equation
[CH2:1]([CH:3]([C:6]1[C:11]2[N:12]([CH2:16][C:17]([O:19][CH:20]([CH3:22])[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:35]N1C(=O)CCC1=O.C(=O)([O-])O.[Na+]>ClC1C=CC=CC=1>[Cl:35][C:9]1[C:10]2[NH:14][C:13](=[O:15])[N:12]([CH2:16][C:17]([O:19][CH:20]([CH3:22])[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

6

Reactant 4

HCID 6547AzobisisobutyronitrileHCID 31398ChlorosuccinimideHCID 516892Sodium BicarbonateHCID 86632855Isopropyl [7-(1-ethylpropyl)-2-oxo-2,3-dihydro-1H-benzimidazol-1-yl]acetate

Product 1

HCID 86632856Isopropyl [4-chloro-7-(1-ethylpropyl)-2-oxo-2,3-dihydro-1H-benzimidazol-1-yl]acetateYield 75.3%

Reagents, catalysts & solvents 1

HCID 7964ChlorobenzeneSolvent

Conditions

Temperature
70 °C

Procedure

To a solution of isopropyl [7-(1-ethylpropyl)-2-oxo-2,3-dihydro-1H-benzimidazol-1-yl]acetate (17.9 g, 58.8 mmol) and 2,2′-azobisisobutyronitrile (966 mg, 5.88 mmol) in chlorobenzene (170 mL) was added portionwise N-chlorosuccinimide (7.85 g, 58.8 mmol) at 65° C., and the mixture was stirred at 70° C. for 3.5 days. After cooling, the reaction mixture was neutralized with saturated aqueous sodium hydrogen carbonate (200 mL), and the aqueous layer was separated and extracted with ethyl acetate (200 mL). The combined organic layer was washed with aqueous sodium chloride (200 mL) and brine (150 mL), dried over anhydrous sodium sulfate and concentrated in vacuo. The residue was purified by silica gel column chromatography eluting with a 15-25% ethyl acetate/n-hexane gradient mixture to give the title compound (15.0 g, 44.3 mmol, 75.3%) as a solid.

Workup

  1. temperatureAfter cooling
  2. customthe aqueous layer was separated
  3. extractionextracted with ethyl acetate (200 mL)
  4. washThe combined organic layer was washed with aqueous sodium chloride (200 mL) and brine (150 mL)
  5. dry with materialdried over anhydrous sodium sulfate
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by silica gel column chromatography
  8. washeluting with a 15-25% ethyl acetate/n-hexane gradient mixture

Sources & evidence

ORD record
ord-99d09a64713e42f58b921623065af749
Source dataset
uspto-grants-2014_07
Patent number
US08785460B2

Reaction notes

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