Sodium Carbonate → 1-phenyl-5-pyridin-4-yl-1H-benzoimidazole

HRID 991501Notes

Reaction equation

HRID 991501 reaction equation
Br[C:2]1[CH:16]=[CH:15][C:5]2[N:6]([C:9]3[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=3)[CH:7]=[N:8][C:4]=2[CH:3]=1.[N:17]1[CH:22]=[CH:21][C:20](B(O)O)=[CH:19][CH:18]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(=O)([O-])[O-].[Na+].[Na+]>C(O)CC.O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[C:9]1([N:6]2[C:5]3[CH:15]=[CH:16][C:2]([C:20]4[CH:21]=[CH:22][N:17]=[CH:18][CH:19]=4)=[CH:3][C:4]=3[N:8]=[CH:7]2)[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1

Participants

8

Reactant 4

HCID 10340Sodium CarbonateHCID 11776TriphenylphosphineHCID 2734379(Pyridin-4-yl)boronic acidHCID 120181715-Bromo-1-phenyl-1H-benzoimidazole

Product 1

HCID 184142461-phenyl-5-pyridin-4-yl-1H-benzoimidazoleYield 66.2%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolvent2×HCID 10311-PropanolSolvent2×

Procedure

5-Bromo-1-phenyl-1H-benzoimidazole (11) (13.4 g, 49.1 mmol), 4-pyridylboronic acid (6.63 g, 54.0 mmol), palladium(II) acetate (551 mg, 2.45 mmol) and triphenylphosphine (1.93 g, 7.36 mmol) were stirred in 80 mL of n-PrOH in a flask equipped with a reflux condenser, under Ar. Sodium carbonate (6.24 g, 58.9 mmol) was dissolved in 30 mL of water and the resulting solution was added to the nPrOH mixture. The resulting mixture was degassed three times by alternating vacuum and argon atmoshphere. The reaction was then heated to reflux. After 18 h the reaction as cooled, diluted with water and extracted three times with EtOAc. The combined extracts were washed with sat. NaCl (aq), dried over sodium sulfate, filtered and concentrated. Purification by flash column chromatography (95:5 CH2Cl2/MeOH) afforded 8.82 g of 1-phenyl-5-pyridin4-yl-1H-benzoimidazole (66% yield). 1H NMR (CDCl3) δ8.68 (d, J=6.0 Hz, 2H), 8.18 (s, 1H), 8.17 (s, 1H), 7.63-7.59 (m, 6H), 7.56-7.51 (m, 3H). Mass Spectrometry (for C18H13N3): [M+H]+ 272.1182, theoretical 272.1182.

Workup

  1. customequipped with a reflux condenser, under Ar
  2. customThe resulting mixture was degassed three times
  3. temperatureThe reaction was then heated to reflux
  4. customAfter 18 h the reaction
  5. temperatureas cooled
  6. extractionextracted three times with EtOAc
  7. washThe combined extracts were washed with sat. NaCl (aq)
  8. dry with materialdried over sodium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customPurification by flash column chromatography (95:5 CH2Cl2/MeOH)

Sources & evidence

ORD record
ord-d71875f8b8f848fd8b4378f323afedad
Source dataset
uspto-grants-2002_10
Patent number
US06465484B1

Reaction notes

Loading…