(S)-2-(4-fluoro-phenyl)-2,3-dihydro-1H-pyridin-4-one → 2-(4-Fluoro-phenyl)-4-oxo-3,4-dihydro-2H-pyridine-1-carboxylic acid (2-fluoro-5-methoxy-4-methyl-phenyl)-amide

HRID 1691816Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1691816
[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.[Li]CCCC.[F:20][C:21]1[CH:26]=[C:25]([CH3:27])[C:24]([O:28][CH3:29])=[CH:23][C:22]=1[N:30]=[C:31]=[O:32]>C1COCC1>[F:20][C:21]1[CH:26]=[C:25]([CH3:27])[C:24]([O:28][CH3:29])=[CH:23][C:22]=1[NH:30][C:31]([N:9]1[CH:10]=[CH:11][C:12](=[O:14])[CH2:13][CH:8]1[C:5]1[CH:6]=[CH:7][C:2]([F:1])=[CH:3][CH:4]=1)=[O:32]

Komponenten

5

Edukt 3

HCID 59377679(S)-2-(4-fluoro-phenyl)-2,3-dihydro-1H-pyridin-4-oneHCID 593778971-Fluoro-2-isocyanato-4-methoxy-5-methyl-benzeneHCID 178418339Butyllithium

Produkt 1

HCID 669077172-(4-Fluoro-phenyl)-4-oxo-3,4-dihydro-2H-pyridine-1-carboxylic acid (2-fluoro-5-methoxy-4-methyl-phenyl)-amideAusbeute 24,9 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel

Versuchsvorschrift

(S)-2-(4-Fluoro-phenyl)-2,3-dihydro-1H-pyridin-4-one (95 mg, 0.50 mmol) was dissolved in THF and cooled to −40° C. n-BuLi (1.1 eq, 0.34 ml of 2.5M solution) was added dropwise, forming a purple suspension. The mixture was allowed to stir for 30 minutes until the purple color changed to white. 1-Fluoro-2-isocyanato-4-methoxy-5-methyl-benzene (1 eq, 90 mg) was added. The mixture was allowed to stir for 1 hour at −40° C., then allowed to warm to room temperature and stirred for 2 hours. The reaction was quenched with saturated ammonium chloride solution. The mixture was diluted with water and extracted with ethyl acetate. The combined organic extracts were washed with brine, dried over anhydrous sodium sulfate, and concentrated in vacuo. The residue was purified by flash chromatography (gradient 9:1 to 1:1 hexanes/ethyl acetate) to give 2-(4-Fluoro-phenyl)-4-oxo-3,4-dihydro-2H-pyridine-1-carboxylic acid (2-fluoro-5-methoxy-4-methyl-phenyl)-amide (46 mg, 24.7%) as a foam. MS (ES+) m/z 373 (M+H).

Aufarbeitung

  1. additionwas added dropwise
  2. customforming a purple suspension
  3. stirringto stir for 1 hour at −40° C.
  4. stirringstirred for 2 hours
  5. customThe reaction was quenched with saturated ammonium chloride solution
  6. additionThe mixture was diluted with water
  7. extractionextracted with ethyl acetate
  8. washThe combined organic extracts were washed with brine
  9. dry with materialdried over anhydrous sodium sulfate
  10. concentrationconcentrated in vacuo
  11. customThe residue was purified by flash chromatography (gradient 9:1 to 1:1 hexanes/ethyl acetate)

Quellen und Nachweise

ORD-Eintrag
ord-f3b554c6d21340be9342ca7aae6fc32b
Quelldatensatz
uspto-grants-2012_04
Patentnummer
US08153809B2

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