Potassium Carbonate → (4'-{4-[(R)-1-(2-Fluoro-phenyl)-ethoxycarbonylamino]-5-methyl-isoxazol-3-yl}-biphenyl-4-yl)-acetic acid

HRID 2045835Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2045835
[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C@H:8]([O:10][C:11](=[O:26])[NH:12][C:13]1[C:14]([C:19]2[CH:24]=[CH:23][C:22](Br)=[CH:21][CH:20]=2)=[N:15][O:16][C:17]=1[CH3:18])[CH3:9].C([O:29][C:30]([CH2:32][C:33]1[CH:38]=[CH:37][C:36](B(O)O)=[CH:35][CH:34]=1)=[O:31])C.C(=O)([O-])[O-].[K+].[K+]>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.COCCOC>[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C@H:8]([O:10][C:11]([NH:12][C:13]1[C:14]([C:19]2[CH:24]=[CH:23][C:22]([C:36]3[CH:37]=[CH:38][C:33]([CH2:32][C:30]([OH:31])=[O:29])=[CH:34][CH:35]=3)=[CH:21][CH:20]=2)=[N:15][O:16][C:17]=1[CH3:18])=[O:26])[CH3:9]

Komponenten

6

Edukt 3

HCID 11430Potassium CarbonateHCID 457900024-Ethoxycarbonylmethylphenylboronic acidHCID 68184602[3-(4-Bromo-phenyl)-5-methyl-isoxazol-4-yl]-carbamic acid (R)-1-(2-fluoro-phenyl)-ethyl ester

Produkt 1

HCID 49858424(4'-{4-[(R)-1-(2-Fluoro-phenyl)-ethoxycarbonylamino]-5-methyl-isoxazol-3-yl}-biphenyl-4-yl)-acetic acid

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 178418476HCID 178418476, VerbindungKatalysatorHCID 80711,2-DimethoxyethaneLösungsmittel

Reaktionsbedingungen

Temperatur
90 °C

Versuchsvorschrift

[3-(4-Bromo-phenyl)-5-methyl-isoxazol-4-yl]-carbamic acid (R)-1-(2-fluoro-phenyl)-ethyl ester (0.080 g, 0.16 mmol), (4-ethoxycarbonylmethylphenyl)boronic acid, pinacol ester (0.055 g, 0.19 mmol), potassium carbonate (0.055 g, 0.40 mmol), and bis(triphenylphosphine)palladium(II) dichloride (0.011 g, 0.016 mmol) were combined in 2:1 DME:H2O and degassed with N2 for 5 minutes. The reaction was stirred at 90° C. for 3 hours, until no starting material was seen by analytical LCMS. 1N Aqueous LiOH (0.5 mL) was added, and the reaction was stirred at room temperature until no ester starting material was seen by analytical LCMS. After acidic work-up, the crude material was purified by preparative HPLC to give the title compound. Mass spectometric data [M+H]=475.

Aufarbeitung

  1. customH2O and degassed with N2 for 5 minutes
  2. addition1N Aqueous LiOH (0.5 mL) was added
  3. stirringthe reaction was stirred at room temperature until no ester starting material
  4. customAfter acidic work-up, the crude material was purified by preparative HPLC

Quellen und Nachweise

ORD-Eintrag
ord-8f72ed58532c4f7ba32f256a8f81f9a0
Quelldatensatz
uspto-grants-2013_11
Patentnummer
US08592402B2

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