Cesium carbonate → [4-Difluoromethoxy-2-ethyl-8-fluoro-3-(4-thiazol-2-ylbenzyl)quinolin-5-yloxy]acetic acid

HRID 1944299Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1944299
C[O:2][C:3](=[O:39])[CH2:4][O:5][C:6]1[CH:15]=[CH:14][C:13]([F:16])=[C:12]2[C:7]=1[C:8]([O:35][CH:36]([F:38])[F:37])=[C:9]([CH2:19][C:20]1[CH:25]=[CH:24][C:23](B3OC(C)(C)C(C)(C)O3)=[CH:22][CH:21]=1)[C:10]([CH2:17][CH3:18])=[N:11]2.Br[C:41]1[S:42][CH:43]=[CH:44][N:45]=1.O1CCOCC1.C(=O)([O-])[O-].[Cs+].[Cs+]>C(OCC)(=O)C.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[F:37][CH:36]([F:38])[O:35][C:8]1[C:7]2[C:12](=[C:13]([F:16])[CH:14]=[CH:15][C:6]=2[O:5][CH2:4][C:3]([OH:2])=[O:39])[N:11]=[C:10]([CH2:17][CH3:18])[C:9]=1[CH2:19][C:20]1[CH:21]=[CH:22][C:23]([C:41]2[S:42][CH:43]=[CH:44][N:45]=2)=[CH:24][CH:25]=1

Komponenten

7

Edukt 4

HCID 10796Cesium carbonateHCID 312751,4-DioxaneHCID 764302-BromothiazoleHCID 67458783{4-Difluoromethoxy-2-ethyl-8-fluoro-3-[4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)benzyl]quinolin-5-yloxy}acetic acid methyl ester

Produkt 1

HCID 25095818[4-Difluoromethoxy-2-ethyl-8-fluoro-3-(4-thiazol-2-ylbenzyl)quinolin-5-yloxy]acetic acidAusbeute 42,9 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)KatalysatorHCID 8857Ethyl AcetateLösungsmittel

Reaktionsbedingungen

Temperatur
90 °C

Versuchsvorschrift

A mixture of {4-difluoromethoxy-2-ethyl-8-fluoro-3-[4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)benzyl]quinolin-5-yloxy}acetic acid methyl ester (0.052 g), 2-bromothiazole (0.076 g), [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium (0.060 g), 1,4-dioxane (2.0 mL) and 2.0M aqueous cesium carbonate solution (0.19 mL) was heated at 90° C. overnight. The mixture was cooled to room temperature, diluted with ethyl acetate and filtered. The filtrate was concentrated under reduced pressure, and the residue dissolved in tetrahydrofuran (5.0 mL) and 1.0M aqueous lithium hydroxide solution (0.19 mL), and the resulting mixture was stirred at room temperature for 1 hour. The mixture was concentrate to low bulk under reduced pressure, and the residue acidified by the addition 0.1M aqueous hydrochloric acid solution and then extracted with ethyl acetate. The combined extracts were dried over magnesium sulfate and then concentrated under reduced pressure. Purification of the residue by column chromatography on C-18 column gave title compound (0.020 g).

Aufarbeitung

  1. temperatureThe mixture was cooled to room temperature
  2. filtrationfiltered
  3. concentrationThe filtrate was concentrated under reduced pressure
  4. dissolutionthe residue dissolved in tetrahydrofuran (5.0 mL)
  5. concentrationThe mixture was concentrate to low bulk under reduced pressure
  6. additionthe residue acidified by the addition 0.1M aqueous hydrochloric acid solution
  7. extractionextracted with ethyl acetate
  8. dry with materialThe combined extracts were dried over magnesium sulfate
  9. concentrationconcentrated under reduced pressure
  10. customPurification of the residue by column chromatography on C-18 column

Quellen und Nachweise

ORD-Eintrag
ord-8949485628a54b5aa6db3c0a0be8f8a6
Quelldatensatz
uspto-grants-2013_03
Patentnummer
US08394830B2

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