Hydroxylamine → HCID 178494171, compound

HRID 70705Notes

Reaction equation

HRID 70705 reaction equation
[C:1]([C:5]1[CH:10]=[CH:9][C:8](/[C:11](/[C:16]2[CH:21]=[CH:20][C:19]([Cl:22])=[C:18]([O:23][CH3:24])[N:17]=2)=[CH:12]\[CH2:13][C:14]#[N:15])=[CH:7][CH:6]=1)([CH3:4])([CH3:3])[CH3:2].[NH2:25][OH:26].[CH:27]([OH:30])(C)C>>[C:1]([C:5]1[CH:10]=[CH:9][C:8](/[C:11](/[C:16]2[CH:21]=[CH:20][C:19]([Cl:22])=[C:18]([O:23][CH3:24])[N:17]=2)=[CH:12]\[CH2:13][C:14]2[NH:25][O:26][C:27](=[O:30])[N:15]=2)=[CH:7][CH:6]=1)([CH3:4])([CH3:2])[CH3:3]

Participants

4

Reactant 3

HCID 787HydroxylamineHCID 3776IsopropanolHCID 58452831(3E)-4-(4-tert-Butylphenyl)-4-(5-chloro-6-methoxypyridin-2-yl)but-3-enenitrile

Product 1

HCID 178494171HCID 178494171, compoundYield 62%

Procedure

A solution of (3E)-4-(4-tert-butylphenyl)-4-(5-chloro-6-methoxypyridin-2-yl)but-3-enenitrile obtained in Reference Example 4-13 (101 mg) in isopropanol (3 mL) was stirred at 105° C., during which a 50% hydroxylamine solution (0.1 mL) was added dropwise thereto. The mixture was stirred at the same temperature for two hours. The reaction solution was left to cool and then the solvent was evaporated under reduced pressure. Carbonyldiimidazole (72 mg) was added to a solution of the residue in 1,4-dioxane (3 mL), and the mixture was stirred at 120° C. for 30 minutes. Carbonyldiimidazole (55 mg) was further added and the mixture was stirred at 140° C. for 30 minutes. The reaction solution was left to cool and then water was added, followed by extraction with ethyl acetate. The organic layer was washed with brine, dried over sodium sulfate and filtered, after which the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (chloroform:methanol=10:0→9:1) to give 3-[(2E)-3-(4-tert-butylphenyl)-3-(5-chloro-6-methoxypyridin-2-yl)prop-2-en-1-yl]-1,2,4-oxadiazol-5(2H)-one as an orange oil (73 mg, 62%).

Workup

  1. additionwas added dropwise
  2. waitThe reaction solution was left
  3. temperatureto cool
  4. customthe solvent was evaporated under reduced pressure
  5. additionCarbonyldiimidazole (72 mg) was added to a solution of the residue in 1,4-dioxane (3 mL)
  6. stirringthe mixture was stirred at 120° C. for 30 minutes
  7. additionCarbonyldiimidazole (55 mg) was further added
  8. stirringthe mixture was stirred at 140° C. for 30 minutes
  9. waitThe reaction solution was left
  10. temperatureto cool
  11. additionwater was added
  12. extractionfollowed by extraction with ethyl acetate
  13. washThe organic layer was washed with brine
  14. dry with materialdried over sodium sulfate
  15. filtrationfiltered
  16. customafter which the solvent was evaporated under reduced pressure
  17. customThe residue was purified by silica gel column chromatography (chloroform:methanol=10:0→9:1)

Sources & evidence

ORD record
ord-8a84ac815c154b038546d680bfcf6347
Source dataset
uspto-grants-2014_09
Patent number
US08822503B2

Reaction notes

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