Tributyl(4-fluorophenyl)stannane → 7-(4-Fluoro-phenyl)-4-hydroxy-isoquinoline-3-carboxylic acid ethyl ester

HRID 1481157Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1481157
[CH2:1]([O:3][C:4]([C:6]1[N:7]=[CH:8][C:9]2[C:14]([C:15]=1[OH:16])=[CH:13][CH:12]=[C:11](Br)[CH:10]=2)=[O:5])[CH3:2].[F:18][C:19]1[CH:24]=[CH:23][C:22]([Sn](CCCC)(CCCC)CCCC)=[CH:21][CH:20]=1>CN(C=O)C.C(OCC)(=O)C.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[CH2:1]([O:3][C:4]([C:6]1[N:7]=[CH:8][C:9]2[C:14]([C:15]=1[OH:16])=[CH:13][CH:12]=[C:11]([C:22]1[CH:23]=[CH:24][C:19]([F:18])=[CH:20][CH:21]=1)[CH:10]=2)=[O:5])[CH3:2]

Komponenten

6

Edukt 2

HCID 2737524Tributyl(4-fluorophenyl)stannaneHCID 89813095Ethyl 7-bromo-4-hydroxyisoquinoline-3-carboxylate

Produkt 1

HCID 898130357-(4-Fluoro-phenyl)-4-hydroxy-isoquinoline-3-carboxylic acid ethyl esterAusbeute 55 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 178418476HCID 178418476, VerbindungKatalysatorHCID 6228DimethylformamideLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Reaktionsbedingungen

Temperatur
120 °C

Versuchsvorschrift

7-Bromo-4-hydroxy-isoquinoline-3-carboxylic acid ethyl ester (250 mg, 0.8443 mmol) was dissolved in dry DMF and 4 Å molecular sieves were added to maintain dryness. 4-fluorophenyl-tri-n-butylstannane (392 mg, 1.013 mmol) and bis(triphenylphosphine)palladium(II) dichloride (71 mg, 0.1013 mmol) were added sequentially and the reaction heated to 120° C. in an oil bath. Upon completion, the reaction was cooled and diluted with ethyl acetate. The solution was washed with water then brine and the organic phase dried over sodium sulfate. The crude material was purified by medium pressure liquid chromatography (15 to 45% ethyl acetate in hexanes) to give the desired material in 55% yield as a thick yellow oil. 1H NMR (200 MHz, CDCl3): δ ppm=11.88 (s, 1H), 8.83 (s, 1H), 8.41 (d, 1H), 8.05 (s, 1H), 7.93 (d, 1H), 7.66 (m, 2H), 7.18 (t, 2H), 4.57 (q, 2H), 1.52 (t, 3H.)

Aufarbeitung

  1. addition4 Å molecular sieves were added
  2. temperatureto maintain dryness
  3. temperatureUpon completion, the reaction was cooled
  4. washThe solution was washed with water
  5. dry with materialbrine and the organic phase dried over sodium sulfate
  6. customThe crude material was purified by medium pressure liquid chromatography (15 to 45% ethyl acetate in hexanes)

Quellen und Nachweise

ORD-Eintrag
ord-c1adf59fe0944e8c8de281fa0156e174
Quelldatensatz
uspto-grants-2016_08
Patentnummer
US09409892B2

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