Diethyl Malonate → Diethyl 2-(7-fluoro-2-methoxy-1,5-naphthyridin-8-yl)malonate

HRID 527947

Reaktionsgleichung

Reaktionsgleichung von HRID 527947
[C:1]([O:9][CH2:10][CH3:11])(=[O:8])[CH2:2][C:3]([O:5][CH2:6][CH3:7])=[O:4].[H-].[Na+].Br[C:15]1[C:16]([F:27])=[CH:17][N:18]=[C:19]2[C:24]=1[N:23]=[C:22]([O:25][CH3:26])[CH:21]=[CH:20]2.OS([O-])(=O)=O.[Na+]>O1CCOCC1>[CH2:10]([O:9][C:1](=[O:8])[CH:2]([C:15]1[C:24]2[C:19](=[CH:20][CH:21]=[C:22]([O:25][CH3:26])[N:23]=2)[N:18]=[CH:17][C:16]=1[F:27])[C:3]([O:5][CH2:6][CH3:7])=[O:4])[CH3:11]

Komponenten

6

Edukt 4

HCID 7761Diethyl MalonateHCID 24758Sodium hydrideHCID 516919Sodium BisulfateHCID 454803208-Bromo-7-fluoro-2-methoxy-1,5-naphthyridine

Produkt 1

HCID 67131047Diethyl 2-(7-fluoro-2-methoxy-1,5-naphthyridin-8-yl)malonateAusbeute 90 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 312751,4-DioxaneLösungsmittel

Versuchsvorschrift

Diethyl malonate (12.4 mL, 81.7 mmol) was added to a suspension of NaH (3.0 g, 47.9 mmol, 60% in mineral oil) in dioxane (35 mL). The mixture was stirred at rt for 5 min and then heated at 80° C. for 1 h. After cooling to rt, CuBr (1.4 g, 9.6 mmol) and 8-bromo-7-fluoro-2-methoxy-[1,5]naphthyridine (7.0 g, 27.2 mmol, prepared according to WO 2007/122258) were added. The mixture was stirred at 100° C. for 6 h. After cooling to rt, 10% NaHSO4 (100 mL) was added. The mixture was stirred for 30 min at rt. The two layers were decanted and the aq. layer was extracted three times with EA (3×150 mL). The combined org. layers were washed with brine, dried over Na2SO4, filtered and concentrated to dryness. The residue was purified by CC (Hept-EA 3:1 then 1:1) to afford the title intermediate as a yellow oil (8.22 g, 90% yield).

Aufarbeitung

  1. temperatureheated at 80° C. for 1 h
  2. temperatureAfter cooling to rt
  3. stirringThe mixture was stirred at 100° C. for 6 h
  4. temperatureAfter cooling to rt
  5. stirringThe mixture was stirred for 30 min at rt
  6. customThe two layers were decanted
  7. extractionthe aq. layer was extracted three times with EA (3×150 mL)
  8. washlayers were washed with brine
  9. dry with materialdried over Na2SO4
  10. filtrationfiltered
  11. concentrationconcentrated to dryness
  12. customThe residue was purified by CC (Hept-EA 3:1

Quellen und Nachweise

ORD-Eintrag
ord-3b512a5083db4f8b8253aafef9ab4677
Quelldatensatz
uspto-grants-2016_05
Patentnummer
US09346804B2

Verknüpfte Notizen

Wird geladen…