Diisopropylamine → Methyl 5-(4-fluorophenyl)-6-hydroxynicotinate

HRID 1909146Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1909146
Br[C:2]1[C:7](=[O:8])[NH:6][CH:5]=[C:4]([C:9]([O:11][CH3:12])=[O:10])[CH:3]=1.[F:13][C:14]1[CH:19]=[CH:18][C:17](B(O)O)=[CH:16][CH:15]=1.[Na+].O.S(C1C=C(P(C2C=CC=C(S([O-])(=O)=O)C=2)C2C=CC=C(S([O-])(=O)=O)C=2)C=CC=1)([O-])(=O)=O.[Na+].[Na+].C(NC(C)C)(C)C>CN(C=O)C.O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[F:13][C:14]1[CH:19]=[CH:18][C:17]([C:2]2[C:7](=[O:8])[NH:6][CH:5]=[C:4]([C:9]([O:11][CH3:12])=[O:10])[CH:3]=2)=[CH:16][CH:15]=1

Komponenten

8

Edukt 4

HCID 7912DiisopropylamineHCID 2856454-Fluorophenylboronic acidHCID 2764315Methyl 5-bromo-6-hydroxynicotinateHCID 53487040Sodium 3,3',3''-phosphinetriyltribenzenesulfonate hydrate

Produkt 1

HCID 67339481Methyl 5-(4-fluorophenyl)-6-hydroxynicotinateAusbeute 65,5 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 167845palladium(II) acetateKatalysatorHCID 962WaterLösungsmittelHCID 6228DimethylformamideLösungsmittel

Reaktionsbedingungen

Temperatur
125 °C

Versuchsvorschrift

To a solution of methyl 5-bromo-6-oxo-1,6-dihydropyridine-3-carboxylate (0.50 g, 2.16 mmol) in DMF (8.1 mL) and water 2.7 mL) were added (4-fluorophenyl)boronic acid (0.38 g, 2.69 mmol), palladium(II) acetate (36.3 mg, 0.16 mmol), tris(3-sulfonatophenyl)phosphine hydrate sodium salt (0.31 g, 0.49 mmol) and diisopropylamine (1.54 mL, 10.8 mmol). The mixture was heated in the microwave reactor at 125° C. for 15 min. The mixture was filtered and water was added to the filtrate. The mixture was extracted with ethyl acetate and the organic layer was washed with water (3×), brine, dried over sodium sulfate, filtered and concentrated. Purification by silica gel chromatography (100% dichloromethane→70% dichloromethane/ethyl acetate) gave the title compound (0.35 g). MS 248.1 (M+1).

Aufarbeitung

  1. filtrationThe mixture was filtered
  2. additionwater was added to the filtrate
  3. extractionThe mixture was extracted with ethyl acetate
  4. washthe organic layer was washed with water (3×), brine
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customPurification by silica gel chromatography (100% dichloromethane→70% dichloromethane/ethyl acetate)

Quellen und Nachweise

ORD-Eintrag
ord-7fe2dbd998bd44f5a858cda2e4786074
Quelldatensatz
uspto-grants-2013_12
Patentnummer
US08598209B2

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