Hydroxylamine → HCID 178494171, 화합물

HRID 70705노트

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HRID 70705 반응식
[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]

참가 물질

4

반응물 3

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

생성물 1

HCID 178494171HCID 178494171, 화합물수율 62%

실험 절차

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%).

후처리

  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)

출처 및 근거

ORD 기록
ord-8a84ac815c154b038546d680bfcf6347
출처 데이터셋
uspto-grants-2014_09
특허 번호
US08822503B2

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