Pyridine → HCID 86751066, compound

HRID 265282Notes

Reaction equation

HRID 265282 reaction equation
O=[C:2]([C:22]1[CH:27]=[CH:26][C:25]([Cl:28])=[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:29].Cl.[NH2:31][CH2:32][CH2:33][O:34][NH2:35].N1C=CC=CC=1>C(O)C>[ClH:28].[ClH:29].[NH2:31][CH2:32][CH2:33][O:34][N:35]=[C:2]([C:22]1[CH:27]=[CH:26][C:25]([Cl:28])=[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 19078362HCID 19078362, compound

Product 1

HCID 86751066HCID 86751066, compoundYield 105.3%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

A mixture of 1-{1-[4-oxo-4-(4-chlorophenyl)butyl]-4-piperidinyl}-1,3-dihydro-2-benzimidazolone (3.00 g), O-(2-aminoethyl)hydroxylamine dihydrochloride (1.35 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 twice from absolute ethanol/ether to give 2.1 g (53%) of product, mp 140°-145° 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 twice from absolute ethanol/ether

Sources & evidence

ORD record
ord-ad4ebdd453e94b9ca0d46d32a376ddc0
Source dataset
uspto-grants-1997_07
Patent number
US05648367

Reaction notes

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