Cesium carbonate → 2-Chloro-4-((6-nitropyridin-3-yl)oxy)pyridine

HRID 626495

Reaktionsgleichung

Reaktionsgleichung von HRID 626495
Br[C:2]1[CH:3]=[CH:4][C:5]([N+:8]([O-:10])=[O:9])=[N:6][CH:7]=1.C([O-])([O-])=O.[Cs+].[Cs+].[Cl:17][C:18]1[CH:23]=[C:22]([OH:24])[CH:21]=[CH:20][N:19]=1>CN(C=O)C>[Cl:17][C:18]1[CH:23]=[C:22]([O:24][C:2]2[CH:7]=[N:6][C:5]([N+:8]([O-:10])=[O:9])=[CH:4][CH:3]=2)[CH:21]=[CH:20][N:19]=1

Komponenten

5

Edukt 3

HCID 10796Cesium carbonateHCID 8176205-Bromo-2-nitropyridineHCID 178516507HCID 178516507, Verbindung

Produkt 1

HCID 593227792-Chloro-4-((6-nitropyridin-3-yl)oxy)pyridineAusbeute 33 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel

Reaktionsbedingungen

Temperatur
85 °C

Versuchsvorschrift

A solution of 5-bromo-2-nitropyridine (15 g, 73.9 mmol) in DMF (300 mL) was sparged with Ar, treated with Cs2CO3 (48.2 g, 148 mmol) and 2-chloro-4-hydroxypyridine (10.53 g, 81 mmol), sparged again with Ar and heated at 85° C. overnight. The mixture was cooled to RT, filtered through a bed of silica gel, washed thoroughly with EtOAc, and the filtrate treated with 5% LiCl and stirred overnight. The layers were separated, the aqueous layer extracted with additional EtOAc (4×) and the combined organics were dried over Na2SO4 and concentrated to dryness. The residue was dissolved in EtOAc, treated with 5% LiCl, stirred for 1 h, the layers separated and the aqueous layer extracted with EtOAc (3×). The combined organics were dried over Na2SO4, concentrated to dryness and purified via silica gel chromatography (EtOAc/Hex). The material was suspended in MTBE, sonicated and the resulting solid collected via filtration to afford 2-chloro-4-((6-nitropyridin-3-yl)oxy)pyridine (6.06 g, 33%). 1H NMR (400 MHz, DMSO-d6): δ 8.62 (d, J=2.4, 1H), 8.43-8.39 (m, 2H), 8.06 (dd, J=8.8, 2.8 Hz, 1H), 7.36 (d, J=2.0 Hz, 1H), 7.23 (dd, J=5.6, 2.0 Hz, 1H); MS (ESI) m/z: 252.0 (M+H+).

Aufarbeitung

  1. customsparged again with Ar
  2. temperatureThe mixture was cooled to RT
  3. filtrationfiltered through a bed of silica gel
  4. washwashed thoroughly with EtOAc
  5. additionthe filtrate treated with 5% LiCl
  6. customThe layers were separated
  7. extractionthe aqueous layer extracted with additional EtOAc (4×)
  8. dry with materialthe combined organics were dried over Na2SO4
  9. concentrationconcentrated to dryness
  10. dissolutionThe residue was dissolved in EtOAc
  11. additiontreated with 5% LiCl
  12. stirringstirred for 1 h
  13. customthe layers separated
  14. extractionthe aqueous layer extracted with EtOAc (3×)
  15. dry with materialThe combined organics were dried over Na2SO4
  16. concentrationconcentrated to dryness
  17. custompurified via silica gel chromatography (EtOAc/Hex)
  18. customsonicated
  19. filtrationthe resulting solid collected via filtration

Quellen und Nachweise

ORD-Eintrag
ord-7786721a14c14a5da4a7f7909c3ccfc7
Quelldatensatz
uspto-grants-2016_04
Patentnummer
US09309224B2

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