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

HRID 1691782노트

반응식

HRID 1691782 반응식
[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]([CH3:27])[C:24]([O:28][CH3:29])=[CH:23][C:22]=1[CH2:30][C:31](Cl)=[O:32].[Cl-].[NH4+]>C1COCC1>[Br:20][C:21]1[CH:26]=[C:25]([CH3:27])[C:24]([O:28][CH3:29])=[CH:23][C:22]=1[CH2:30][C:31]([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:32]

참가 물질

6

반응물 4

HCID 25517Ammonium ChlorideHCID 59377679(S)-2-(4-fluoro-phenyl)-2,3-dihydro-1H-pyridin-4-oneHCID 59377714(2-Bromo-5-methoxy-4-methyl-phenyl)-acetic acid chlorideHCID 178418339Butyllithium

생성물 1

HCID 59377669(S)-1-[2-(2-bromo-5-methoxy-4-methyl-phenyl)-acetyl]-2-(4-fluoro-phenyl)-2,3-dihydro-1H-pyridin-4-one

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매2회

반응 조건

온도
-78 °C

실험 절차

To a solution of (S)-2-(4-fluoro-phenyl)-2,3-dihydro-1H-pyridin-4-one (80 mg) in THF (1.5 mL) at −78° C. under argon was added n-butyllithium (0.184 mL, 2.5M in hexanes). After ten minutes a solution of (2-bromo-5-methoxy-4-methyl-phenyl)-acetic acid chloride (116 mg) in THF (1 mL) was added. The mixture was stirred at −78° C. for 30 minutes, then at room temperature for 30 minutes. Saturated aqueous ammonium chloride was added and the mixture was extracted with ethyl acetate. The combined organic extracts were washed with brine, dried (Na2SO4), filtered and concentrated to dryness under reduced pressure. Purification of the residue by flash chromatography (hexanes/ethyl acetate gradient) gave (S)-1-[2-(2-bromo-5-methoxy-4-methyl-phenyl)-acetyl]-2-(4-fluoro-phenyl)-2,3-dihydro-1H-pyridin-4-one as a foam. MS (M+H) 433.

후처리

  1. waitat room temperature for 30 minutes
  2. extractionthe mixture was extracted with ethyl acetate
  3. washThe combined organic extracts were washed with brine
  4. dry with materialdried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated to dryness under reduced pressure
  7. customPurification of the residue by flash chromatography (hexanes/ethyl acetate gradient)

출처 및 근거

ORD 기록
ord-31e9837716044988a13be9915aea90a6
출처 데이터셋
uspto-grants-2012_04
특허 번호
US08153808B2

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