Triethylamine → 5-Formyl-1-(3-(1-piperidinyl)phenyl)benzimidazole oxime

HRID 324732Notes

Reaction equation

HRID 324732 reaction equation
[C:1]([C:3]1[CH:23]=[CH:22][C:6]2[N:7]([C:10]3[CH:15]=[CH:14][CH:13]=[C:12]([N:16]4[CH2:21][CH2:20][CH2:19][CH2:18][CH2:17]4)[CH:11]=3)[CH:8]=[N:9][C:5]=2[CH:4]=1)#[N:2].Cl.[OH:25]N.C(N(CC)CC)C>C(O)=O.O.[Ni]>[CH:1](=[N:2][OH:25])[C:3]1[CH:23]=[CH:22][C:6]2[N:7]([C:10]3[CH:15]=[CH:14][CH:13]=[C:12]([N:16]4[CH2:17][CH2:18][CH2:19][CH2:20][CH2:21]4)[CH:11]=3)[CH:8]=[N:9][C:5]=2[CH:4]=1

Participants

7

Reactant 3

HCID 8471Triethylamine2×HCID 443297Hydroxyamine hydrochlorideHCID 22741908HCID 22741908, compound

Product 1

HCID 867566235-Formyl-1-(3-(1-piperidinyl)phenyl)benzimidazole oximeYield 70%

Reagents, catalysts & solvents 3

HCID 935NickelCatalystHCID 284Formic AcidSolventHCID 962WaterSolvent2×

Procedure

To a solution of 3a1 (3.83 g, 12.9 mmol) in a mixture of formic acid (45 ml) and water (15 ml) was added Raney Ni (2.14 g, slurry in water). The mixture was refluxed with stirring for 3 hours. After cooling the mixture was filtered through celite and the filtrate was evaporated to dryness. The residue was partitioned between ethyl acetate and aqueous sodium bicarbonate (1M). The organic phase was dried over sodium sulfate and concentrated under reduced pressure. The concentrate was eluted through a short silica gel is column with ethyl acetate. Evaporation of the solvent left 5-formyl-1-(3-(1-piperidinyl)phenyl)-benzimidazole (3.86 g, 100%) as an oil. This oil was dissolved in refluxing ethanol (15 ml). Hydroxyl amine hydrochloride (2.64 g, 38.0 mmol) and triethylamine (1.70 ml) was added and reflux was continued for 5 hours. The cooled mixture was rendered basic by addition of triethylamine. Water was added and the pricipitate was filtered off, washed with water and dried to yield 3b1 (2.89 g, 70%). M.p. 213-214° C.

Workup

  1. temperatureThe mixture was refluxed
  2. temperatureAfter cooling the mixture
  3. filtrationwas filtered through celite
  4. customthe filtrate was evaporated to dryness
  5. customThe residue was partitioned between ethyl acetate and aqueous sodium bicarbonate (1M)
  6. dry with materialThe organic phase was dried over sodium sulfate
  7. concentrationconcentrated under reduced pressure
  8. washThe concentrate was eluted through a short silica gel
  9. customEvaporation of the solvent
  10. waitleft 5-formyl-1-(3-(1-piperidinyl)phenyl)-benzimidazole (3.86 g, 100%) as an oil
  11. dissolutionThis oil was dissolved
  12. temperaturein refluxing ethanol (15 ml)
  13. temperaturereflux
  14. waitwas continued for 5 hours
  15. filtrationthe pricipitate was filtered off
  16. washwashed with water
  17. customdried

Sources & evidence

ORD record
ord-4eab5ad1aeb443a6a850b1c623377e71
Source dataset
uspto-grants-2001_04
Patent number
US06218547B1

Reaction notes

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