Potassium Carbonate → 5-(4-Formylphenoxy)pyrazine-2-carbonitrile

HRID 130873

Reaktionsgleichung

Reaktionsgleichung von HRID 130873
O1CC[O:3][CH:2]1[C:6]1[CH:11]=[CH:10][C:9]([OH:12])=[C:8](OC)[CH:7]=1.Cl[C:16]1[N:17]=[CH:18][C:19]([C:22]#[N:23])=[N:20][CH:21]=1.C([O-])([O-])=O.[K+].[K+]>CC(N(C)C)=O.C(CC(C)(C)C)(C)C>[CH:2]([C:6]1[CH:7]=[CH:8][C:9]([O:12][C:16]2[N:17]=[CH:18][C:19]([C:22]#[N:23])=[N:20][CH:21]=2)=[CH:10][CH:11]=1)=[O:3]

Komponenten

6

Edukt 3

HCID 11430Potassium CarbonateHCID 3463544-(1,3-Dioxolan-2-yl)-2-methoxyphenolHCID 122957285-Chloropyrazine-2-carbonitrile

Produkt 1

HCID 597301105-(4-Formylphenoxy)pyrazine-2-carbonitrileAusbeute 81,8 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 109072,2,4-TrimethylpentaneLösungsmittelHCID 31374DimethylacetamideLösungsmittel

Reaktionsbedingungen

Temperatur
110 °C

Versuchsvorschrift

Dissolve 4-[1,3]dioxolan-2-yl-2-phenol (Example 388, Part C2) (1.70 g, 10.2 mmol), 5-chloropyrazine-2-carbonitrile (Example 404, Part A) (1.50 g, 10.7 mmol) and K2CO3 (3.71 g, 26.9 mmol) in DMA (27.0 mL) and isooctane (13.4 mL). Heat at 110° C. for about 2.25 hours. Cool to room temperature and quench with water (100 mL). Extract with dichloromethane (3×100 mL). Wash the extract with saturated aqueous NaHCO3 (1×50 mL) and brine (1×75 mL). Dry the organic layer over Na2SO4, filter and concentrate. Purify by flash chromatography, eluting with 0-30% ethyl acetate in hexanes. Concentrate the eluant, then take the solid up in 88% formic acid (46 mL) and stir at room temperature for 4 hours. Dilute the reaction mixture with water (50 mL). Extract with dichloromethane (2×100 mL). Wash the extract with saturated aqueous NaHCO3 (1×50 mL), dry over Na2SO4, filter and concentrate. Purify by flash chromatography eluting with 30% ethyl acetate in hexanes to give the title compound (1.88 g, 77.7%): TOF MS ES+ 225.1 (M)+, HRMS calcd for C12H7N3O2 225.0538 (M)+, found 225.0527, time 0.38 min; HPLC [YMC-Pack Pro C-18 (150×4.6 mm, S-5 microm), 0.1% TFA/acetonitrile in 0.1% TFA/water at 1.0 mL/min, 20-99% over 23 min], tR=11.5 min, 100% purity.

Aufarbeitung

  1. temperatureCool to room temperature
  2. customquench with water (100 mL)
  3. extractionExtract with dichloromethane (3×100 mL)
  4. washWash the
  5. extractionextract with saturated aqueous NaHCO3 (1×50 mL) and brine (1×75 mL)
  6. dry with materialDry the organic layer over Na2SO4
  7. filtrationfilter
  8. concentrationconcentrate
  9. customPurify by flash chromatography
  10. washeluting with 0-30% ethyl acetate in hexanes
  11. concentrationConcentrate the eluant
  12. additionDilute the reaction mixture with water (50 mL)
  13. extractionExtract with dichloromethane (2×100 mL)
  14. washWash the
  15. extractionextract with saturated aqueous NaHCO3 (1×50 mL)
  16. dry with materialdry over Na2SO4
  17. filtrationfilter
  18. concentrationconcentrate
  19. customPurify by flash chromatography
  20. washeluting with 30% ethyl acetate in hexanes

Quellen und Nachweise

ORD-Eintrag
ord-158b98446c814c1dbf44570961f4e053
Quelldatensatz
uspto-grants-2008_06
Patentnummer
US07381719B2

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