Sodium hydride → tert-Butyl 3-(tert-butoxycarbonylphenylmethyl)-5-cyano-2-oxo-2,3-dihydro-benzimidazole-1-carboxylate

HRID 1631962Notes

Reaction equation

HRID 1631962 reaction equation
[C:1]([O:5][C:6]([N:8]1[C:12]2[CH:13]=[CH:14][C:15]([C:17]#[N:18])=[CH:16][C:11]=2[NH:10][C:9]1=[O:19])=[O:7])([CH3:4])([CH3:3])[CH3:2].[H-].[Na+].[C:22]([O:26][C:27](=[O:36])[CH:28](Br)[C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1)([CH3:25])([CH3:24])[CH3:23]>CN(C=O)C.C(OCC)(=O)C>[C:1]([O:5][C:6]([N:8]1[C:12]2[CH:13]=[CH:14][C:15]([C:17]#[N:18])=[CH:16][C:11]=2[N:10]([CH:28]([C:27]([O:26][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:36])[C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=2)[C:9]1=[O:19])=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 11000147Tert-butyl 2-bromo-2-phenylacetateHCID 249009585-Cyano-2-oxo-2,3-dihydro-benzoimidazole-1-carboxylic acid tert-butyl ester

Product 1

HCID 66755109tert-Butyl 3-(tert-butoxycarbonylphenylmethyl)-5-cyano-2-oxo-2,3-dihydro-benzimidazole-1-carboxylateYield 78.9%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

To a chilled solution of 5-cyano-2-oxo-2,3-dihydro-benzoimidazole-1-carboxylic acid tert-butyl ester (808 mg, 3.1 mmol) in dry DMF (15 mL) was added NaH (60% dispersion mineral oil, 131 mg, 3.3 mmol) under N2 atmosphere. The reaction was stirred at room temperature for 15 min. Then at 0° C., a solution of bromophenylacetic acid tert-butyl ester (887 mg, 3.3 mmol) in DMF (5 mL) was added. The reaction was stirred at room temperature for 2 hours, diluted with ethyl acetate, washed with water, with a saturated NH4Cl aqueous solution, brine, dried over Na2SO4, filtered and concentrated in vacuo. The residue was purified by flash chromatography in silica gel using 15% ethyl acetate in n-heptane as eluent to afford 3-(tert-butoxycarbonyl-phenyl methyl)-5-cyano-2-oxo-2,3-dihydro-benzoimidazole-1-carboxylic acid tert-butyl ester (VIIc) (1.1 g, 78%) as a white solid.

Workup

  1. stirringThe reaction was stirred at room temperature for 2 hours
  2. washwashed with water, with a saturated NH4Cl aqueous solution, brine
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified by flash chromatography in silica gel using 15% ethyl acetate in n-heptane as eluent

Sources & evidence

ORD record
ord-260c8e5e77784ce99259530eb96ebb57
Source dataset
uspto-grants-2014_07
Patent number
US08791148B2

Reaction notes

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