Reaktion #5038

Reaktionsgleichung

3-bromo-6-ethylpyridazine

ethyl isonipecotate

diisopropylethylamine

methylpyrrolidine

→

Formula IV

6-ethyl-3-(4-hydroxymethyl-1-piperidinyl)pyridazine

Lösungsmittel

water

Reaktionsbedingungen

Aufarbeitung

1. 1
   workup.ADDITIONwas added to the mixture
2. 2
   Extraktionthe contents were extracted with methylene chloride
3. 3
   Waschenthen washed twice with water and once with brine
4. 4
   Sonstigethe solvent evaporated in vacuo
5. 5
   WaschenThe resulting oil was eluted through a short silica gel plug with 80% ethyl acetate and 20% hexanes
6. 6
   Sonstigedried in vacuo
7. 7
   TemperaturThe reaction was chilled on ice
8. 8
   Sonstigequenched by dropwise addition of water
9. 9
   SonstigeThe slurry was dried
10. 10
    workup.ADDITIONtreated with charcoal
11. 11
    Filtrationfiltered

Vorschrift

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 ).

Quelle