Diisopropylamine → Ethyl 5-(2-fluoro-4-methylphenyl)nicotinate

HRID 1909148

Reaktionsgleichung

Reaktionsgleichung von HRID 1909148
Br[C:2]1[CH:3]=[N:4][CH:5]=[C:6]([CH:12]=1)[C:7]([O:9][CH2:10][CH3:11])=[O:8].[F:13][C:14]1[CH:19]=[C:18]([CH3:20])[CH:17]=[CH:16][C:15]=1B(O)O.[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+]>C(#N)C.O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[F:13][C:14]1[CH:19]=[C:18]([CH3:20])[CH:17]=[CH:16][C:15]=1[C:2]1[CH:3]=[N:4][CH:5]=[C:6]([CH:12]=1)[C:7]([O:9][CH2:10][CH3:11])=[O:8]

Komponenten

9

Edukt 5

HCID 7912DiisopropylamineHCID 140785Ethyl 5-bromopyridine-3-carboxylateHCID 516892Sodium BicarbonateHCID 2783132(2-Fluoro-4-methylphenyl)boronic acidHCID 6099338Trisodium 3,3',3''-phosphinetriyltris(benzene-1-sulphonate)

Produkt 1

HCID 67338384Ethyl 5-(2-fluoro-4-methylphenyl)nicotinateAusbeute 102,1 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 167845palladium(II) acetateKatalysatorHCID 962WaterLösungsmittelHCID 6342AcetonitrileLösungsmittel

Reaktionsbedingungen

Temperatur
80 °C

Versuchsvorschrift

To a solution of ethyl 5-bromonicotinate (0.58 g, 2.53 mmol) in acetonitrile (15 mL) and water (5 mL) were added (2-fluoro-4-methylphenyl)boronic acid (0.47 g, 3.04 mmol), 3,3′,3″-phosphinidynetris(benzenesulfonic acid) trisodium salt (0.22 g, 0.38 mmol), palladium(II)acetate (28.4 mg, 0.13 mmol) and diisopropylamine (0.90 mL, 6.32 mmol). The mixture was heated to 80° C. After 1 h, the mixture was cooled to ambient temperature and saturated aqueous NaHCO3 was added. The mixture was extracted with ethyl acetate (3×). The combined organic extracts were washed with brine, dried over sodium sulfate, filtered and concentrated. Purification by silica gel chromatography (100% hexanes→70% hexanes/ethyl acetate) gave the title compound (0.67 g). MS 260.1 (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 brine
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customPurification by silica gel chromatography (100% hexanes→70% hexanes/ethyl acetate)

Quellen und Nachweise

ORD-Eintrag
ord-394117abaf164211983341ba147be7a0
Quelldatensatz
uspto-grants-2013_12
Patentnummer
US08598209B2

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