Ammonium Chloride → (S)-1-[2-(2-bromo-5-difluoromethoxy-4-methoxy-phenyl)-acetyl]-2-(4-fluoro-phenyl)-2,3-dihydro-1H-pyridin-4-one

HRID 1691787ノート

反応式

HRID 1691787 の反応式
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C@@H:8]2[CH2:13][C:12](=[O:14])[CH:11]=[CH:10][NH:9]2)=[CH:4][CH:3]=1.C([Li])CCC.[Br:20][C:21]1[CH:26]=[C:25]([O:27][CH3:28])[C:24]([O:29][CH:30]([F:32])[F:31])=[CH:23][C:22]=1[CH2:33][C:34](Cl)=[O:35].[Cl-].[NH4+]>C1COCC1>[Br:20][C:21]1[CH:26]=[C:25]([O:27][CH3:28])[C:24]([O:29][CH:30]([F:32])[F:31])=[CH:23][C:22]=1[CH2:33][C:34]([N:9]1[CH:10]=[CH:11][C:12](=[O:14])[CH2:13][C@H:8]1[C:5]1[CH:6]=[CH:7][C:2]([F:1])=[CH:3][CH:4]=1)=[O:35]

参加物

6

反応物 4

HCID 25517Ammonium ChlorideHCID 59377679(S)-2-(4-fluoro-phenyl)-2,3-dihydro-1H-pyridin-4-oneHCID 59377702(2-Bromo-5-difluoromethoxy-4-methoxy-phenyl)-acetic acid chlorideHCID 178418339Butyllithium

生成物 1

HCID 46830905(S)-1-[2-(2-bromo-5-difluoromethoxy-4-methoxy-phenyl)-acetyl]-2-(4-fluoro-phenyl)-2,3-dihydro-1H-pyridin-4-one収率 17.3%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒2 回

反応条件

温度
-78 °C

実験手順

To 108 mg of (S)-2-(4-fluoro-phenyl)-2,3-dihydro-1H-pyridin-4-one in 8 ml THF (anhydrous, inhibitor free) at −78° C. under argon was added 0.18 ml of 2.5 M n-butyl lithium in hexanes. The mixture was stirred at −78° C. for 10 minutes and then 118 mg of (2-bromo-5-difluoromethoxy-4-methoxy-phenyl)-acetic acid chloride dissolved in 2 ml THF was added. The solution was stirred at −78° C. for 30 minutes, then allowed to warm to room temperature for 30 minutes with stirring. To this mixture was then added 10 ml saturated aqueous ammonium chloride. The mixture was extracted with ethyl acetate, the organic layer was dried over sodium sulfate, filtered and the solvent was removed in vacuo. Chromatography (20% Ethyl acetate in hexanes) gave 30 mg (S)-1-[2-(2-bromo-5-difluoromethoxy-4-methoxy-phenyl)-acetyl]-2-(4-fluoro-phenyl)-2,3-dihydro-1H-pyridin-4-one. MS (M+1) 485.

後処理

  1. additionwas added
  2. stirringThe solution was stirred at −78° C. for 30 minutes
  3. temperatureto warm to room temperature for 30 minutes
  4. stirringwith stirring
  5. extractionThe mixture was extracted with ethyl acetate
  6. dry with materialthe organic layer was dried over sodium sulfate
  7. filtrationfiltered
  8. customthe solvent was removed in vacuo

出典と根拠

ORDレコード
ord-adaf8f704cf54cfd8061aa9c74934f8f
出典データセット
uspto-grants-2012_04
特許番号
US08153808B2

反応ノート

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