Sodium hydride → (E)-2-Styryl-1-(3-trifluoromethylpyridin-2-yl)-1H-benzimidazole

HRID 50869

Reaction equation

HRID 50869 reaction equation
[CH:1](/[C:9]1[NH:13][C:12]2[CH:14]=[CH:15][CH:16]=[CH:17][C:11]=2[N:10]=1)=[CH:2]\[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.[H-].[Na+].Cl[C:21]1[C:26]([C:27]([F:30])([F:29])[F:28])=[CH:25][CH:24]=[CH:23][N:22]=1>CC(N(C)C)=O.[Cu]>[CH:1](/[C:9]1[N:10]([C:21]2[C:26]([C:27]([F:30])([F:29])[F:28])=[CH:25][CH:24]=[CH:23][N:22]=2)[C:11]2[CH:17]=[CH:16][CH:15]=[CH:14][C:12]=2[N:13]=1)=[CH:2]\[C:3]1[CH:4]=[CH:5][CH:6]=[CH:7][CH:8]=1

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 5898332-Chloro-3-(trifluoromethyl)pyridineHCID 57080032-[(E)-2-phenylethenyl]-1H-benzimidazole

Product 1

HCID 22736647(E)-2-Styryl-1-(3-trifluoromethylpyridin-2-yl)-1H-benzimidazoleYield 5%

Reagents, catalysts & solvents 2

HCID 23978CopperCatalystHCID 31374DimethylacetamideSolvent2×

Conditions

Temperature
0 °C

Procedure

To a stirred solution of (E)-2-styryl-1H-benzimidazole (0.49 g, 2.2 mmol) in dimethylacetamide (20 ml) at 0° C. under a nitrogen atmosphere was added sodium hydride (0.11 g, 2.8 mmol). After stirring at 0° C. for 20 min. and then at room temperature for 30 min., a solution of 2-Chloro-3-trifluoromethylpyridine (0.60 g, 3.3 mmol) in dimethylacetamide (5 ml) was added. The resulting mixture was heated to reflux for about 3 h 20 min. After cooling, copper bronze (0.45 g, 7.1 mg-atom) was added and heating was continued for 9 h 20 min. The reaction mixture was filtered through a pad of celite and the filtrate was diluted with dichloromethane (200 ml), washed consecutively with water (3×200 ml) and brine (100 ml), dried (magnesium sulfate) and concentrated to dryness. Purification by column chromatography (silica gel, 150 g; n-hexane/ethyl acetate (2/1)) followed by recrystallization from a mixture of isopropyl ether and n-hexane yielded 37 mg (5%) of the titled compound as white solids. MW: 365.36; mp: 156.0-157.0° C.; 1H-NMR (CDCl3) δ: 8.96 (1H, dd, J=4.8, 1.8 Hz), 8.36 (1H, dd, J=8.1, 1.8 Hz), 7.90 (1H, d, J=15.8 Hz), 7.84 (1H, d, J=8.1 Hz), 7.76 (1H, d, J=8.1, 4.8 Hz), 7.45-7.20 (7H, m), 6.92 (1H, d, J=7.7 Hz), 6.47 (1H, d, J=15.8 Hz).

Workup

  1. waitat room temperature for 30 min.
  2. temperatureThe resulting mixture was heated
  3. temperatureto reflux for about 3 h 20 min
  4. temperatureAfter cooling
  5. temperatureheating
  6. waitwas continued for 9 h 20 min
  7. filtrationThe reaction mixture was filtered through a pad of celite
  8. additionthe filtrate was diluted with dichloromethane (200 ml)
  9. washwashed consecutively with water (3×200 ml) and brine (100 ml)
  10. dry with materialdried (magnesium sulfate)
  11. concentrationconcentrated to dryness
  12. customPurification by column chromatography (silica gel, 150 g; n-hexane/ethyl acetate (2/1))
  13. customfollowed by recrystallization from a mixture of isopropyl ether and n-hexane

Sources & evidence

ORD record
ord-61cef2dd26354f48a48b428e9f443eab
Source dataset
uspto-grants-2004_03
Patent number
US06713482B2

Linked notes

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