Pyridine → HCID 73474168, compound

HRID 1939323Notes

Reaction equation

HRID 1939323 reaction equation
O=[C:2]([C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1)[CH2:3][CH2:4][CH2:5][N:6]1[CH2:11][CH2:10][CH:9]([N:12]2[C:16]3[CH:17]=[CH:18][CH:19]=[CH:20][C:15]=3[NH:14][C:13]2=[O:21])[CH2:8][CH2:7]1.[ClH:28].Cl.[NH2:30][CH2:31][CH2:32][O:33][NH2:34].N1C=CC=CC=1>C(O)C>[ClH:28].[ClH:28].[NH2:30][CH2:31][CH2:32][O:33][N:34]=[C:2]([C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1)[CH2:3][CH2:4][CH2:5][N:6]1[CH2:11][CH2:10][CH:9]([N:12]2[C:16]3[CH:17]=[CH:18][CH:19]=[CH:20][C:15]=3[NH:14][C:13]2=[O:21])[CH2:8][CH2:7]1

Participants

5

Reactant 3

HCID 1049PyridineHCID 143623262-(O-aminooxy)ethylamine dihydrochlorideHCID 19078339HCID 19078339, compound

Product 1

HCID 73474168HCID 73474168, compoundYield 47.8%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

A mixture of 1-[1-(4-oxo-4-phenylbutyl)-4-piperidinyl]-1,3-dihydro-2-benzimidazolone (3.85 g), O-(2-aminoethyl)hydroxylamine dihydrochloride (1.89 g), 3 equivalents of pyridine, and absolute ethanol (75 ml) was heated under reflux, under nitrogen, with stirring, for three hrs. The reaction mixture was partitioned between 10% sodium hydroxide solution and ethyl acetate. The layers were separated and the aqueous phase extracted with ethyl acetate. The combined organic extracts were dried over anhydrous sodium sulfate, filtered, and the filtrate was evaporated. The residue was taken up in toluene and evaporated. The residue was purified by flash chromatography (180:19:1 dichloromethane/methanol/ammonium hydroxide). The appropriate fractions were collected and evaporated. The residue was dissolved in absolute ethanol and treated with ethereal hydrogen chloride. The solvent was evaporated and the residue was taken up in hot 2-propanol and chilled. The precipitate was collected and recrystallized from 2-propanol and then twice from ethanol/ether to give 1.5 g (29%) of product, mp 175°-180° C. (dec).

Workup

  1. temperaturewas heated
  2. temperatureunder reflux, under nitrogen
  3. customThe reaction mixture was partitioned between 10% sodium hydroxide solution and ethyl acetate
  4. customThe layers were separated
  5. extractionthe aqueous phase extracted with ethyl acetate
  6. dry with materialThe combined organic extracts were dried over anhydrous sodium sulfate
  7. filtrationfiltered
  8. customthe filtrate was evaporated
  9. customevaporated
  10. customThe residue was purified by flash chromatography (180:19:1 dichloromethane/methanol/ammonium hydroxide)
  11. customThe appropriate fractions were collected
  12. customevaporated
  13. dissolutionThe residue was dissolved in absolute ethanol
  14. additiontreated with ethereal hydrogen chloride
  15. customThe solvent was evaporated
  16. temperaturechilled
  17. customThe precipitate was collected
  18. customrecrystallized from 2-propanol

Sources & evidence

ORD record
ord-0999bf0e0503479fa963db4864f2f548
Source dataset
uspto-grants-1997_12
Patent number
US05696142

Reaction notes

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