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

温度

140 °C

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 ).

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

ORDレコード

ord-e7615e51d1964e48ab83367a353ca96f

出典データセット

uspto-grants-1993_09

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US05242924