4-Methylpyridine → (R)-4-(4-bromophenyl)-1-(pyridin-4-yl)-4-o-tolylbutan-2-one

HRID 1617834Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1617834
[CH3:1][C:2]1[CH:7]=[CH:6][N:5]=[CH:4][CH:3]=1.C([Li])CCC.[Br:13][C:14]1[CH:19]=[CH:18][C:17]([C@H:20]([C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][C:29]=2[CH3:34])[CH2:21][C:22](N(OC)C)=[O:23])=[CH:16][CH:15]=1.C(=O)([O-])O.[Na+]>O1CCCC1.C(OCC)(=O)C>[Br:13][C:14]1[CH:15]=[CH:16][C:17]([C@H:20]([C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][C:29]=2[CH3:34])[CH2:21][C:22](=[O:23])[CH2:1][C:2]2[CH:7]=[CH:6][N:5]=[CH:4][CH:3]=2)=[CH:18][CH:19]=1

Komponenten

7

Edukt 4

HCID 79634-MethylpyridineHCID 516892Sodium BicarbonateHCID 71813344(R)-3-(4-Bromophenyl)-N-methoxy-N-methyl-3-o-tolylpropanamideHCID 178418339Butyllithium

Produkt 1

HCID 66666163(R)-4-(4-bromophenyl)-1-(pyridin-4-yl)-4-o-tolylbutan-2-oneAusbeute 51 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 8028TetrahydrofuranLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Versuchsvorschrift

To a solution of 4-methylpyridine (308 mg, 3.31 mmol) in tetrahydrofuran at −78° C. was added dropwise n-butyllithium solution (1.6 M in hexane, 2.07 mL, 3.31 mmol). The reaction mixture was stirred for 1 hour at room temperature and cooled down again to −78° C. (R)-3-(4-bromo-phenyl)-N-methoxy-N-methyl-3-o-tolyl-propionamide (example 142, step 1; 400 mg, 1.1 mmol) was added and the reaction mixture was stirred at room temperature for 3 hours. A saturated solution of sodium hydrogencarbonate and ethyl acetate were added, the phases were separated and the inorganic one was extracted with ethyl acetate (2×). The combined organic layers were washed with brine, dried over sodium sulfate, filtered and concentrated in vacuo. The crude product was purified by flash chromatography on silica gel (10% methanol in dichloromethane) to yield the title compound as a yellow oil (51%), MS (ESI+): m/z=394.0 ([M+H]+).

Aufarbeitung

  1. additionwas added
  2. stirringthe reaction mixture was stirred at room temperature for 3 hours
  3. customthe phases were separated
  4. extractionthe inorganic one was extracted with ethyl acetate (2×)
  5. washThe combined organic layers were washed with brine
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThe crude product was purified by flash chromatography on silica gel (10% methanol in dichloromethane)

Quellen und Nachweise

ORD-Eintrag
ord-5a6132f835d844049163f0accac50737
Quelldatensatz
uspto-grants-2014_07
Patentnummer
US08765730B2

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