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

HRID 1776366
Notizen
Druckvorschau

Reaktionsgleichung

Reaktionsgleichung von HRID 1776366
Br[C:2]1[C:3](=[O:18])[C:4]([CH3:17])([CH3:16])[O:5][C:6]=1[C:7]1[CH:12]=[CH:11][C:10]([O:13][CH3:14])=[C:9]([Cl:15])[CH:8]=1.CC1(C)C(C)(C)OB([C:27]2[CH:44]=[CH:43][C:30]([O:31][CH2:32][C:33]3[CH:42]=[CH:41][C:40]4[C:35](=[CH:36][CH:37]=[CH:38][CH:39]=4)[N:34]=3)=[CH:29][CH:28]=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]>[Cl:15][C:9]1[CH:8]=[C:7]([C:6]2[O:5][C:4]([CH3:17])([CH3:16])[C:3](=[O:18])[C:2]=2[C:27]2[CH:28]=[CH:29][C:30]([O:31][CH2:32][C:33]3[CH:42]=[CH:41][C:40]4[C:35](=[CH:36][CH:37]=[CH:38][CH:39]=4)[N:34]=3)=[CH:43][CH:44]=2)[CH:12]=[CH:11][C:10]=1[O:13][CH3:14]
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 593547584-bromo-5-(3-chloro-4-methoxyphenyl)-2,2-dimethylfuran-3(2H)-one

Produkt 1

HCID 445943265-(3-chloro-4-methoxyphenyl)-2,2-dimethyl-4-(4-(quinolin-2-ylmethoxy)phenyl)furan-3(2H)-oneAusbeute 24,6 %

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 solution of 4-bromo-5-(3-chloro-4-methoxyphenyl)-2,2-dimethylfuran-3(2H)-one 0.34 g, 1.021 mmol), 2-((4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenoxy)methyl)quinoline (0.37 g, 1.021 mmol), and Cs2CO3 (1.67 g, 5.130 mmol) in toluene (6 mL) and water (3 mL) was degassed. Then, Pd(dppf)Cl2(0.167 g, 0.204 mmol) was added under an inert atmosphere and the solution was again degassed. Then the reaction mixture was refluxed for 1 h, filtered through a pad of Celite® and the filtrate was diluted with EtOAc (20 mL). The combined organic layers were washed with water (5 mL) and 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 5-(3-chloro-4-methoxyphenyl)-2,2-dimethyl-4-(4-(quinolin-2-ylmethoxy)phenyl)furan-3(2H)-one (122 mg, 23%) as a solid. 1H NMR (500 MHz, d6-DMSO): δ 8.42 (d, J=8.5 Hz, 1 H), 8.02 (t, J=7.9 Hz, 2 H), 7.79 (t, 7.4 Hz, 1 H), 7.70 (d, J=8.2 Hz, 1 H), 7.65-7.59 (m, 2H), 7.51 (d, J=8.1 Hz, 1 H), 7.22-7.18 (m, 3 H), 7.12 (d, J=7.5 Hz, 2 H), 5.40 (s, 2H), 3.91 (s, 3H), 1.46 (s, 6 H). MS: [M+Na]: m/z=508.2, [M+H]: m/z=486.2. HPLC: 96%, 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. customthe solution was again degassed
  2. temperatureThen the reaction mixture was refluxed for 1 h
  3. filtrationfiltered through a pad of Celite®
  4. additionthe filtrate was diluted with EtOAc (20 mL)
  5. washThe combined organic layers were washed with water (5 mL) and brine (5 mL)
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customto obtain the crude product
  10. customThe crude material was purified via silica gel column chromatography

Quellen und Nachweise

ORD-Eintrag
ord-9349537e1f5b4bb882acbfd53df4640f
Quelldatensatz
uspto-grants-2016_02
DOI
10.6084/m9.figshare.5104873.v1
Patentnummer
US09265767B2

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