Sodium hydride → 1-Tert-butyl 3-ethyl 2-(6-chloropyridazin-3-yl)malonate

HRID 1925132Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1925132
[C:1]([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])(=[O:8])[CH2:2][C:3]([O:5][CH2:6][CH3:7])=[O:4].[H-].[Na+].[Cl:16][C:17]1[N:18]=[N:19][C:20](Cl)=[CH:21][CH:22]=1>O1CCOCC1>[Cl:16][C:17]1[N:18]=[N:19][C:20]([CH:2]([C:3]([O:5][CH2:6][CH3:7])=[O:4])[C:1]([O:9][C:10]([CH3:12])([CH3:11])[CH3:13])=[O:8])=[CH:21][CH:22]=1

Komponenten

5

Edukt 3

HCID 24758Sodium hydrideHCID 673313,6-DichloropyridazineHCID 96345tert-Butyl ethyl malonate

Produkt 1

HCID 592330361-Tert-butyl 3-ethyl 2-(6-chloropyridazin-3-yl)malonateAusbeute 143,3 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 312751,4-DioxaneLösungsmittel

Reaktionsbedingungen

Temperatur
0 °C

Versuchsvorschrift

tert-Butyl ethyl malonate (41.3 ml, 211 mmol) was added drop-wise to a suspension of sodium hydride (19.33 g, 483 mmol) in dioxane (1000 mL) at 0° C. The reaction was stirred at 0° C. for 1 hr and then allowed to warm to ambient temperature. 3,6-dichloropyridazine (30 g, 201 mmol) was then added portion wise at 25° C. The reaction was stirred at reflux for 2 hrs and then solvent was removed via rotary evaporation. The resulting residue was dissolved in EtOAc (400 mL), and the organic phase was washed with saturated NaHCO3 (400 mL), dried over MgSO4, filtered, and concentrated to dryness via rotary evaporation. This reaction was repeated. The combined crude residues from both batches was purified via MPLC (Hex:EtOAc, 8:2) to provide the title compound, 1-tert-butyl 3-ethyl 2-(6-chloropyridazin-3-yl)malonate (86.5 g, 288 mmol, 71.3%). 1H NMR (400 MHz, DMSO-d6) δ ppm 1.12-1.23 (m, 3 H) 1.36-1.52 (m, 9 H) 4.20 (m, J=10.71, 7.22, 7.22, 3.85, 3.85 Hz, 2 H) 5.29 (s, 1 H) 7.85 (d, J=8.84 Hz, 1 H) 7.99 (d, J=8.84 Hz, 1 H). ESI-MS:m/z 301.2 (M+H)+.

Aufarbeitung

  1. temperatureto warm to ambient temperature
  2. stirringThe reaction was stirred
  3. temperatureat reflux for 2 hrs
  4. customsolvent was removed via rotary evaporation
  5. dissolutionThe resulting residue was dissolved in EtOAc (400 mL)
  6. washthe organic phase was washed with saturated NaHCO3 (400 mL)
  7. dry with materialdried over MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated to dryness via rotary evaporation
  10. customwas purified via MPLC (Hex:EtOAc, 8:2)

Quellen und Nachweise

ORD-Eintrag
ord-afa7c482c5d34a94a9a1163299142ab1
Quelldatensatz
uspto-grants-2012_05
Patentnummer
US08178534B2

Notizen zur Reaktion

Wird geladen…