1-Methylpyrrolidine → 6-Ethyl-3-(4-hydroxymethyl-1-piperidinyl)pyridazine

HRID 4942

Reaktionsgleichung

Reaktionsgleichung von HRID 4942
Br[C:2]1[N:3]=[N:4][C:5]([CH2:8][CH3:9])=[CH:6][CH:7]=1.[NH:10]1[CH2:20][CH2:19][CH:13]([C:14](OCC)=[O:15])[CH2:12][CH2:11]1.C(N(C(C)C)CC)(C)C.CN1CCCC1>O>[CH2:8]([C:5]1[N:4]=[N:3][C:2]([N:10]2[CH2:20][CH2:19][CH:13]([CH2:14][OH:15])[CH2:12][CH2:11]2)=[CH:7][CH:6]=1)[CH3:9]

Komponenten

6

Edukt 4

HCID 84541-MethylpyrrolidineHCID 70770Ethyl 4-piperidinecarboxylateHCID 81531DiisopropylethylamineHCID 197973093-Bromo-6-ethylpyridazine

Produkt 1

HCID 197973066-Ethyl-3-(4-hydroxymethyl-1-piperidinyl)pyridazine

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 962WaterLösungsmittel

Reaktionsbedingungen

Temperatur
140 °C

Versuchsvorschrift

1.67 g (0.011 mol) of 3-bromo-6-ethylpyridazine was added to 1.5 mL (10 mmol) ethyl isonipecotate and 3.5 mL (20 mmol) diisopropylethylamine and 5 mL N methylpyrrolidine (NMP). This mixture was heated to 140° C. for 4 hours. Upon cooling 100 mL of water was added to the mixture and the contents were extracted with methylene chloride then washed twice with water and once with brine and the solvent evaporated in vacuo. The resulting oil was eluted through a short silica gel plug with 80% ethyl acetate and 20% hexanes and dried in vacuo. This intermediate was taken up in 25 mL THF and was exposed to 3-fold excess lithium aluminum hydride with stirring under nitrogen for 1 hour. The reaction was chilled on ice and quenched by dropwise addition of water. The slurry was dried, treated with charcoal and filtered yielding 6-ethyl-3-(4-hydroxymethyl-1-piperidinyl)pyridazine (Formula IV: R1 =C2H5 ; Y=CH2 ).

Aufarbeitung

  1. additionwas added to the mixture
  2. extractionthe contents were extracted with methylene chloride
  3. washthen washed twice with water and once with brine
  4. customthe solvent evaporated in vacuo
  5. washThe resulting oil was eluted through a short silica gel plug with 80% ethyl acetate and 20% hexanes
  6. customdried in vacuo
  7. temperatureThe reaction was chilled on ice
  8. customquenched by dropwise addition of water
  9. customThe slurry was dried
  10. additiontreated with charcoal
  11. filtrationfiltered

Quellen und Nachweise

ORD-Eintrag
ord-e7615e51d1964e48ab83367a353ca96f
Quelldatensatz
uspto-grants-1993_09
Patentnummer
US05242924

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