Diisopropylamine → Methyl 5-(4-fluorophenyl)-6-oxo-1-(3-oxobutan-2-yl)-1,6-dihydropyridine-3-carboxylate

HRID 1909155

Reaktionsgleichung

Reaktionsgleichung von HRID 1909155
Br[C:2]1[C:7](=[O:8])[N:6]([CH:9]([C:11](=[O:13])[CH3:12])[CH3:10])[CH:5]=[C:4]([C:14]([O:16][CH3:17])=[O:15])[CH:3]=1.[F:18][C:19]1[CH:24]=[CH:23][C:22](B(O)O)=[CH:21][CH:20]=1.[Na+].[Na+].[Na+].P(C1C=C(S([O-])(=O)=O)C=CC=1)(C1C=C(S([O-])(=O)=O)C=CC=1)C1C=C(S([O-])(=O)=O)C=CC=1.C(NC(C)C)(C)C.C(=O)(O)[O-].[Na+]>CN(C)C=O.O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[F:18][C:19]1[CH:24]=[CH:23][C:22]([C:2]2[C:7](=[O:8])[N:6]([CH:9]([C:11](=[O:13])[CH3:12])[CH3:10])[CH:5]=[C:4]([C:14]([O:16][CH3:17])=[O:15])[CH:3]=2)=[CH:21][CH:20]=1

Komponenten

9

Edukt 5

HCID 7912DiisopropylamineHCID 2856454-Fluorophenylboronic acidHCID 516892Sodium BicarbonateHCID 6099338Trisodium 3,3',3''-phosphinetriyltris(benzene-1-sulphonate)HCID 67338151Methyl 5-bromo-6-oxo-1-(3-oxobutan-2-yl)-1,6-dihydropyridine-3-carboxylate

Produkt 1

HCID 67338493Methyl 5-(4-fluorophenyl)-6-oxo-1-(3-oxobutan-2-yl)-1,6-dihydropyridine-3-carboxylate

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 167845palladium(II) acetateKatalysatorHCID 962WaterLösungsmittel2×HCID 6228DimethylformamideLösungsmittel

Reaktionsbedingungen

Temperatur
80 °C

Versuchsvorschrift

To a solution of methyl 5-bromo-6-oxo-1-(3-oxobutan-2-yl)-1,6-dihydropyridine-3-carboxylate (11.3 g, 37.4 mmol) in N,N-dimethylformamide (112 mL) and water (37 mL) were added 4-fluorophenylboronic acid (6.28 g, 44.9 mmol), palladium acetate (0.17 g, 0.75 mmol), 3,3′,3″-phosphinidynetris(benzenesulfonic acid) trisodium salt (1.28 g, 2.24 mmol) and diisopropylamine (13.3 mL, 94.0 mmol). The reaction mixture was heated to 80° C. After 30 min, the mixture was cooled to ambient temperature. Saturated aqueous sodium bicarbonate and water were added. The mixture was extracted with ethyl acetate (3×). The combined organic extracts were washed with water (3×), brine, dried over magnesium sulfate, filtered and concentrated. Purification by silica gel chromatography (100% dichloromethane→80% dichloromethane/ethyl acetate) gave the title compound. MS 318.2 (M+1).

Aufarbeitung

  1. temperaturethe mixture was cooled to ambient temperature
  2. extractionThe mixture was extracted with ethyl acetate (3×)
  3. washThe combined organic extracts were washed with water (3×), brine
  4. dry with materialdried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customPurification by silica gel chromatography (100% dichloromethane→80% dichloromethane/ethyl acetate)

Quellen und Nachweise

ORD-Eintrag
ord-89367e96c07f45b7866ac7f2f6b4ff2f
Quelldatensatz
uspto-grants-2013_12
Patentnummer
US08598209B2

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