反应详情

3-Aminopropanol (12.84 g, 0.171 mole) was added to a suspension of 50% sodium hydride in mineral oil (7.96 g, 0.166 mole) in 180 mL of dry DMF and the mixture was warmed to 80°-83°. A solution of 2-chloro-6-piperidinomethylpyridine (34.0 g, 0.161 mole) [prepared in Step A] in 180 mL of dry DMF was then added dropwise and when complete, the temperature was raised to 125°-128° for 3 hours followed by 17 hours at ambient temperature. The precipitated salts were removed by filtration and the solvent stripped under vacuum. The oily residue was dissolved in methylene chloride, washed with water, dried and the solvent evaporated. This residue was redissolved in acetonitrile and extracted with skelly B. After removing the solvent the crude oil was purified by flash chromatography on 270 g of silica gel (230-400 mesh) using a gradient elution of methanol-methylene chloride and evaporated to give the title product as a yellow oil, 21.63 g (48.4%).

1. temperaturethe mixture was warmed to 80°-83°
2. temperaturewhen complete, the temperature was raised to 125°-128° for 3 hours
3. customThe precipitated salts were removed by filtration
4. dissolutionThe oily residue was dissolved in methylene chloride
5. washwashed with water
6. customdried
7. customthe solvent evaporated
8. dissolutionThis residue was redissolved in acetonitrile
9. extractionextracted with skelly B
10. customAfter removing the solvent the crude oil
11. customwas purified by flash chromatography on 270 g of silica gel (230-400 mesh)
12. washa gradient elution of methanol-methylene chloride
13. customevaporated