Potassium Fluoride → Methyl 2-(2,6-difluoro-4-hydroxyphenyl)thiazole-4-carboxylate

HRID 521936Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 521936
Br[C:2]1[S:3][CH:4]=[C:5]([C:7]([O:9][CH3:10])=[O:8])[N:6]=1.[F:11][C:12]1[CH:17]=[C:16]([OH:18])[CH:15]=[C:14]([F:19])[C:13]=1B(O)O.[F-].[K+]>O1CCCC1.O.CC(C)([P](C(C)(C)C)([Pd][P](C(C)(C)C)(C(C)(C)C)C(C)(C)C)C(C)(C)C)C>[F:11][C:12]1[CH:17]=[C:16]([OH:18])[CH:15]=[C:14]([F:19])[C:13]=1[C:2]1[S:3][CH:4]=[C:5]([C:7]([O:9][CH3:10])=[O:8])[N:6]=1

Komponenten

7

Edukt 3

HCID 522689Potassium FluorideHCID 2763213Methyl 2-bromothiazole-4-carboxylateHCID 459336202,6-Difluoro-4-hydroxybenzeneboronic acid

Produkt 1

HCID 136377230Methyl 2-(2,6-difluoro-4-hydroxyphenyl)thiazole-4-carboxylateAusbeute 41,1 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 178418851HCID 178418851, VerbindungKatalysatorHCID 962WaterLösungsmittelHCID 8028TetrahydrofuranLösungsmittel

Reaktionsbedingungen

Temperatur
120 °C

Versuchsvorschrift

To a suspension of methyl 2-bromothiazole-4-carboxylate (500 mg, 2.16 mmol), 2,6-difluoro-4-hydroxyphenylboronic acid (2 equiv., 767 mg) and potassium fluoride (3.3 equiv., 414 mg) in tetrahydrofuran (10 mL) and water (1 mL) was added bis(tri-tert-butylphosphine)palladium(0) (0.1 equiv., 110 mg) and the mixture was heated to 120° C. for 15 min in the microwave reactor. After in vacuo concentration, the reaction mixture was purified by CombiFlash (0 to 100% EtOAc in heptane) to provide 241 mg of the title compound as a ˜1:1 mixture with methyl 2-bromothiazole-4-carboxylate, which was used directly without further purification.

Aufarbeitung

  1. concentrationAfter in vacuo concentration
  2. customthe reaction mixture was purified by CombiFlash (0 to 100% EtOAc in heptane)

Quellen und Nachweise

ORD-Eintrag
ord-504fae86a77148f69a34eb17da84e96c
Quelldatensatz
uspto-grants-2016_05
Patentnummer
US09328106B2

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