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Cesium carbonate → 2,2-dimethyl-4-(4-(quinolin-2-ylmethoxy)phenyl)-5-(thiazol-4-yl)furan-3(2H)-one

HRID 1425904
Notizen
Druckvorschau

Reaktionsgleichung

Reaktionsgleichung von HRID 1425904
Br[C:2]1[C:3](=[O:14])[C:4]([CH3:13])([CH3:12])[O:5][C:6]=1[C:7]1[N:8]=[CH:9][S:10][CH:11]=1.CC1(C)C(C)(C)OB([C:23]2[CH:40]=[CH:39][C:26]([O:27][CH2:28][C:29]3[CH:38]=[CH:37][C:36]4[C:31](=[CH:32][CH:33]=[CH:34][CH:35]=4)[N:30]=3)=[CH:25][CH:24]=2)O1.C([O-])([O-])=O.[Cs+].[Cs+]>C1(C)C=CC=CC=1.O.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]>[CH3:12][C:4]1([CH3:13])[C:3](=[O:14])[C:2]([C:23]2[CH:24]=[CH:25][C:26]([O:27][CH2:28][C:29]3[CH:38]=[CH:37][C:36]4[C:31](=[CH:32][CH:33]=[CH:34][CH:35]=4)[N:30]=3)=[CH:39][CH:40]=2)=[C:6]([C:7]2[N:8]=[CH:9][S:10][CH:11]=2)[O:5]1
KomponentenVersuchsvorschriftAufarbeitungQuellen und NachweiseNotizen zur Reaktion

Komponenten

7

Edukt 3

HCID 10796Cesium carbonateHCID 583680032-((4-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)phenoxy)methyl)quinolineHCID 593548524-bromo-2,2-dimethyl-5-(thiazol-4-yl)furan-3(2H)-one

Produkt 1

HCID 593547932,2-dimethyl-4-(4-(quinolin-2-ylmethoxy)phenyl)-5-(thiazol-4-yl)furan-3(2H)-oneAusbeute 18,9 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 44119782
Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)
Katalysator
HCID 962WaterLösungsmittel
HCID 1140TolueneLösungsmittel

Versuchsvorschrift

A mixture of 4-bromo-2,2-dimethyl-5-(thiazol-4-yl) furan-3(2H)-one (0.1 g, 0.37 mmol), 2-((4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenoxy)methyl)quinoline (0.164 g, 0.454 mmol), and Cs2CO3 (0.673 g, 2.06 mmol) in toluene (1 mL) and water (1 mL) was degassed and Pd(dppf)Cl2 (0.067 g, 0.082 mmol) was added under an inert atmosphere, and degassed once more. Then the reaction was refluxed for 2 h and was filtered through a pad of Celite®, the filtrate was diluted with EtOAc (10 mL), washed with water (5 mL), brine (5 mL), dried over Na2SO4, filtered and concentrated in vacuo to obtain the crude product. The crude material was purified via silica gel column chromatography to afford 2,2-dimethyl-4-(4-(quinolin-2-ylmethoxy)phenyl)-5-(thiazol-4-yl) furan-3(2H)-one (30 mg, 18%) as a solid. 1H NMR (500 MHz, d6-DMSO): δ 9.17 (s, 1H), 8.43 (d, J=8.5 Hz, 1H), 8.30 (s, 1H), 8.02-7.98 (m, 2H), 7.80 (t, J=8.2 Hz, 1H), 7.70 (d, J=8.2 Hz, 1H), 7.62 (t, J=8.5 Hz, 1H), 7.24 (d, J=7.5 Hz, 2H), 7.08 (d, J=7.4 Hz, 2H), 5.38 (s, 2H), 1.42 (s, 6H). MS: [M+H]: m/z=429.1. HPLC: 97.9% (RT-2.36 min), Column: Acquity BEH-C-18, 50×2.1 mm, 1.7 um. Mobile Phase: 0.025% TFA in Water (A), ACN (B), Flow rate: 0.5 ml/min (Gradient).

Aufarbeitung

  1. customwas degassed
  2. customdegassed once more
  3. temperatureThen the reaction was refluxed for 2 h
  4. filtrationwas filtered through a pad of Celite®
  5. additionthe filtrate was diluted with EtOAc (10 mL)
  6. washwashed with water (5 mL), brine (5 mL)
  7. dry with materialdried over Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customto obtain the crude product
  11. customThe crude material was purified via silica gel column chromatography

Quellen und Nachweise

ORD-Eintrag
ord-e49d29bee4974eea8e7c27c8fb8196d8
Quelldatensatz
uspto-grants-2015_01
DOI
10.6084/m9.figshare.5104873.v1
Patentnummer
US08933074B2

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