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

HRID 481980ノート

反応式

HRID 481980 の反応式
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

参加物

7

反応物 4

HCID 807Iodine2 回HCID 793424-chloro-N-methylpiperidineHCID 5462224MagnesiumHCID 19064553N-methyl-N-methoxy 2-(4-acetamidophenoxy)acetamide

生成物 1

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

試薬・触媒・溶媒 2

HCID 112011,1-Dibromoethane触媒HCID 8028Tetrahydrofuran溶媒

反応条件

温度
0 °C

実験手順

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 After the exothermic reaction no longer maintained reflux temperature, the reaction mixture was heated at reflux for 30 minutes and was then cooled to 0° C. To the cold mixture was added the previously prepared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.

後処理

  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

出典と根拠

ORDレコード
ord-e1ff3663367d447fbbd9479ae00b1b43
出典データセット
uspto-grants-1998_08
特許番号
US05792763

反応ノート

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