Ethyl bromoacetate → HCID 69789022, compound

HRID 488743Notes

Reaction equation

HRID 488743 reaction equation
[Br:1][C:2]1[CH:26]=[CH:25][C:5]([CH2:6][C:7]23[CH2:24][CH2:23][CH2:22][CH:21]=[C:8]2[N:9]([C:13]2[CH:18]=[C:17]([Cl:19])[CH:16]=[C:15]([Cl:20])[CH:14]=2)[C:10](=[O:12])[NH:11]3)=[CH:4][CH:3]=1.[H-].[Na+].Br[CH2:30][C:31]([O:33][CH2:34][CH3:35])=[O:32]>CN(C=O)C>[CH2:34]([O:33][C:31](=[O:32])[CH2:30][C:8]12[CH2:21][CH2:22][CH2:23][CH2:24][C:7]1([CH2:6][C:5]1[CH:25]=[CH:26][C:2]([Br:1])=[CH:3][CH:4]=1)[NH:11][C:10](=[O:12])[N:9]2[C:13]1[CH:14]=[C:15]([Cl:20])[CH:16]=[C:17]([Cl:19])[CH:18]=1)[CH3:35]

Participants

5

Reactant 3

HCID 7748Ethyl bromoacetateHCID 24758Sodium hydrideHCID 9846654HCID 9846654, compound

Product 1

HCID 69789022HCID 69789022, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

3a-(4-Bromo-benzyl)-1-(3,5-dichlorophenyl)-1,3,3a,4,5,6-hexahydro-benzimidazol-2-one (190 mg) (0.42 mmol) in DMF (5 ml) was carefully dropped on a suspension of NaH 60% (20.2 mg) (1.2 eq) in DMF (5 ml) at RT. The reaction mixture was stirred 1 h at RT, then ethyl bromoacetate (0.094 ml) (2.0 eq) was added. After one night at RT, the mixture was heated to 100° C. for 8 h, then the reaction mixture was poured on water and extracted with tBuOMe. The organic layer was washed with water, dried over Na2SO4 and concentrated. The residue was purified on SiO2 chromatography (eluent EtOAc/cyclohexane—1/10) to give [7a-(4-Bromo-benzyl)-3-(3,5-dichlorophenyl)-2-oxo-2,3,5,6,7,7a-hexahydro-benzimidazol-3a-yl]-acetic acid ethyl ester (30.2 mg) as a yellow oil. 1H NMR (CDCl3): 7.35 (2H, d), 7.10 (1H, m), 6.95 (2H, d), 6.8 (2H, m), 4.95 (1H, m), 4.45 (1H, d), 4.2 (2H, q), 3.7 (1H, d), 2.9 (1H, d), 2.8 (1H, d), 2.45-2.1 (2H, m), 2.0-1.8 (4H, m), 1.25 (3H, t).

Workup

  1. waitAfter one night at RT
  2. temperaturethe mixture was heated to 100° C. for 8 h
  3. additionthe reaction mixture was poured on water
  4. extractionextracted with tBuOMe
  5. washThe organic layer was washed with water
  6. dry with materialdried over Na2SO4
  7. concentrationconcentrated
  8. customThe residue was purified on SiO2 chromatography (eluent EtOAc/cyclohexane—1/10)

Sources & evidence

ORD record
ord-08ee9488a5564cb4a34ab014697dca4d
Source dataset
uspto-grants-2005_12
Patent number
US06974815B2

Reaction notes

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