Ethyl cyanoacetate → Cyano-(4-methoxy-2-nitro-phenyl)-acetic acid ethyl ester

HRID 1913426

Reaktionsgleichung

Reaktionsgleichung von HRID 1913426
[C:1]([CH2:3][C:4]([O:6][CH2:7][CH3:8])=[O:5])#[N:2].[H-].[Na+].Cl[C:12]1[CH:17]=[CH:16][C:15]([O:18][CH3:19])=[CH:14][C:13]=1[N+:20]([O-:22])=[O:21]>CN(C=O)C.[F-].[Cs+]>[CH2:7]([O:6][C:4](=[O:5])[CH:3]([C:1]#[N:2])[C:12]1[CH:17]=[CH:16][C:15]([O:18][CH3:19])=[CH:14][C:13]=1[N+:20]([O-:22])=[O:21])[CH3:8]

Komponenten

6

Edukt 3

HCID 7764Ethyl cyanoacetateHCID 24758Sodium hydrideHCID 251404-Chloro-3-nitroanisole

Produkt 1

HCID 11086625Cyano-(4-methoxy-2-nitro-phenyl)-acetic acid ethyl esterAusbeute 87 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 25953Cesium fluorideKatalysatorHCID 6228DimethylformamideLösungsmittel2×

Versuchsvorschrift

Ethyl cyanoacetate (2.56 mL, 24.0 mmol) was added dropwise to a suspension of 959 mg of NaH (60%, 24.0 mmol) in 10 mL of DMF. The mixture was stirred for 1 h at room temperature. CsF (61 mg, 0.4 mmol) and a solution of 4-chloro-3-nitro-anisole (1.5 g, 8.0 mmol) in 2 mL of DMF were added and the mixture was stirred overnight at 70° C. The reaction mixture was cooled to room temperature and was quenched by the addition of 5 mL of water. Aqueous 1N HCl (5 mL) was added to adjust the pH to 3-4 and the mixture was diluted with dichloromethane. The organic layer was washed with saturated brine, dried over Na2SO4, and dried in vacuo. The crude product was purified on a Biotage (Biotage Inc.) 50 g silica column, eluting with 0-40% EtOAc in heptane over 40 minutes to provide 1.83 g (87%) of cyano-(4-methoxy-2-nitro-phenyl)-acetic acid ethyl ester.

Aufarbeitung

  1. stirringthe mixture was stirred overnight at 70° C
  2. temperatureThe reaction mixture was cooled to room temperature
  3. customwas quenched by the addition of 5 mL of water
  4. additionAqueous 1N HCl (5 mL) was added
  5. additionthe mixture was diluted with dichloromethane
  6. washThe organic layer was washed with saturated brine
  7. dry with materialdried over Na2SO4
  8. customdried in vacuo
  9. customThe crude product was purified on a Biotage (Biotage Inc.) 50 g silica column
  10. washeluting with 0-40% EtOAc in heptane over 40 minutes

Quellen und Nachweise

ORD-Eintrag
ord-787dbb9468c6412a852339dfba28a500
Quelldatensatz
uspto-grants-2013_12
Patentnummer
US08609680B2

Verknüpfte Notizen

Wird geladen…