Sodium hydride → [1-(3,4-Dichloro-benzyl)-2-propyl-1H-benzoimidazol-5-yl]-phenyl-methanone

HRID 1595311Notes

Reaction equation

HRID 1595311 reaction equation
[C:1]1([C:7]([C:9]2[CH:20]=[CH:19][C:12]3[NH:13][C:14]([CH2:16][CH2:17][CH3:18])=[N:15][C:11]=3[CH:10]=2)=[O:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[H-].[Na+].[Cl:23][C:24]1[CH:25]=[C:26]([CH:29]=[CH:30][C:31]=1[Cl:32])[CH2:27]Br>CN(C=O)C>[Cl:23][C:24]1[CH:25]=[C:26]([CH:29]=[CH:30][C:31]=1[Cl:32])[CH2:27][N:13]1[C:12]2[CH:19]=[CH:20][C:9]([C:7]([C:1]3[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=3)=[O:8])=[CH:10][C:11]=2[N:15]=[C:14]1[CH2:16][CH2:17][CH3:18]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 6397264-(Bromomethyl)-1,2-dichlorobenzeneHCID 178439943HCID 178439943, compound

Product 1

HCID 21705040[1-(3,4-Dichloro-benzyl)-2-propyl-1H-benzoimidazol-5-yl]-phenyl-methanoneYield 50%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of phenyl-(2-propyl-1H-benzoimidazol-5-yl)methanone (5.28 g; 0.02 mol) in DMF (80 mL) was stirred under an atmosphere of nitrogen. Sodium hydride (60% dispersion in oil, 0.8 g; 0.02 mol) was added. The mixture was then stirred for 0.5 hour at ambient temperature. 3,4-dichlorobenzyl bromide (4.8 g; 0.02 mol) was then added in portions. The mixture was stirred at 80-90° C. for 3.5 hours, then at ambient temperature for 18 hours. The solvent was evaporated under vacuum. The residue was extracted with ethyl acetate (300 mL) and washed with water (2×200 mL). The organic phase was evaporated. Purification was achieved by flash chromatography on silica gel (EtOAc/Hexane; 1:9 to 1:3). Recrystallization from ethyl acetate affords the tide compound (4.2 g; 50% yield) as a white solid, m.p. 168-169° C. Anal. Calcd. for C24H20Cl2N2O: C, 68.09; H, 4.76; N, 6.62. Found: C, 67.70; H, 4.46; N, 6.49. Mass spectrum (DEI; M+) m/z 422, 424, 426. 1H-NMR (DMSO -d6; 400 MHz) δ7.94 (d, 1H), 7.73 (d, 2H), 7.64-7.72 (m, 3H), 7.59 (m, 1H), 7.56 (t, 2H), 7.47 (d, 1H), 6.98 (dd, 1H), 5.59 (s, 2H), 2.84 (t, 2H), 1.76 (m, 2H) and 0.94 ppm (t, 3H).

Workup

  1. stirringThe mixture was stirred at 80-90° C. for 3.5 hours
  2. waitat ambient temperature for 18 hours
  3. customThe solvent was evaporated under vacuum
  4. extractionThe residue was extracted with ethyl acetate (300 mL)
  5. washwashed with water (2×200 mL)
  6. customThe organic phase was evaporated
  7. customPurification
  8. customRecrystallization from ethyl acetate
  9. customaffords the tide compound (4.2 g; 50% yield) as a white solid, m.p. 168-169° C

Sources & evidence

ORD record
ord-6c1518151e554c40b63258b1ecf1346f
Source dataset
uspto-grants-2001_09
Patent number
US06288100B1

Reaction notes

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