Iodine → 1-Methyl-4-(2-(4-acetamidophenoxy)acetyl)piperidine

HRID 481980노트

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HRID 481980 반응식
II.[Mg].[CH3:4][N:5]1[CH2:10][CH2:9][CH:8](Cl)[CH2:7][CH2:6]1.CN(OC)[C:14](=[O:27])[CH2:15][O:16][C:17]1[CH:22]=[CH:21][C:20]([NH:23][C:24](=[O:26])[CH3:25])=[CH:19][CH:18]=1>BrC(Br)C.O1CCCC1>[CH3:4][N:5]1[CH2:10][CH2:9][CH:8]([C:14](=[O:27])[CH2:15][O:16][C:17]2[CH:22]=[CH:21][C:20]([NH:23][C:24](=[O:26])[CH3:25])=[CH:19][CH:18]=2)[CH2:7][CH2:6]1

참가 물질

7

반응물 4

HCID 807Iodine2회HCID 793424-chloro-N-methylpiperidineHCID 5462224MagnesiumHCID 19064553N-methyl-N-methoxy 2-(4-acetamidophenoxy)acetamide

생성물 1

HCID 190645761-Methyl-4-(2-(4-acetamidophenoxy)acetyl)piperidine수율 47%

시약·촉매·용매 2

HCID 112011,1-Dibromoethane촉매HCID 8028Tetrahydrofuran용매

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온도
0 °C

실험 절차

A crystal of iodine was added to 0.45 gm (18.7 mMol) magnesium turnings covered with 6 mL tetrahydrofuran. To this mixture were added 5-6 drops of dibromoethane and the mixture was heated with a heat gun to initiate the reaction. Once the iodine color disappeared, 2 mL (15 mMol) 1-methyl-4-chloropiperidine were added and heating continued for an additional 30 seconds. After the exothermic reaction no longer maintained reflux temperature, the reaction mixture was heated at reflux for 30 minutes and was then cooled to 0° C. To the cold mixture was added the previously prepared N-methyl-N-methoxy 2-(4-acetamidophenoxy)acetamide and the resulting mixture stirred for 30 minutes at 0° C. and then an additional hour after warming to room temperature. The reaction was quenched by the addition of water and the resulting mixture extracted well with ethyl acetate. The combined organic extracts were washed saturated aqueous ammonium chloride, dried over magnesium sulfate, and concentrated under reduced pressure. The resulting residue was subjected to silica gel chromatography, eluting with dichloromethane containing 5% methanol. Fractions shown to contain product were combined and concentrated under reduced pressure to provide 0.90 gm (47%) of the desired ketone.

후처리

  1. temperaturethe mixture was heated with a heat gun
  2. customthe reaction
  3. temperatureheating
  4. customAfter the exothermic reaction
  5. temperatureno longer maintained
  6. temperaturereflux temperature
  7. temperaturethe reaction mixture was heated
  8. temperatureat reflux for 30 minutes
  9. temperaturean additional hour after warming to room temperature
  10. customThe reaction was quenched by the addition of water
  11. extractionthe resulting mixture extracted well with ethyl acetate
  12. washThe combined organic extracts were washed saturated aqueous ammonium chloride
  13. dry with materialdried over magnesium sulfate
  14. concentrationconcentrated under reduced pressure
  15. washeluting with dichloromethane containing 5% methanol
  16. concentrationconcentrated under reduced pressure

출처 및 근거

ORD 기록
ord-e1ff3663367d447fbbd9479ae00b1b43
출처 데이터셋
uspto-grants-1998_08
특허 번호
US05792763

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