反応 #5038

反応方程式

3-bromo-6-ethylpyridazine

ethyl isonipecotate

diisopropylethylamine

methylpyrrolidine

→

Formula IV

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

溶媒

water

反応条件

後処理

1. 1
   workup.ADDITIONwas added to the mixture
2. 2
   抽出the contents were extracted with methylene chloride
3. 3
   洗浄then washed twice with water and once with brine
4. 4
   その他the solvent evaporated in vacuo
5. 5
   洗浄The resulting oil was eluted through a short silica gel plug with 80% ethyl acetate and 20% hexanes
6. 6
   その他dried in vacuo
7. 7
   温度The reaction was chilled on ice
8. 8
   その他quenched by dropwise addition of water
9. 9
   その他The slurry was dried
10. 10
    workup.ADDITIONtreated with charcoal
11. 11
    ろ過filtered

実験手順

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 ).

出典