Water → 6-Benzyl-5,6,7,8-tetrahydro-1,6-naphthyridin-2(1H)-one

1-Benzyl-4-piperidone (15 g, 79.3 mmol) and pyrrolidine (7.5 mL, 90 mmol) were dissolved in toluene (90 mL) and the solution was heated under reflux, with the removal of water under Dean and Stark conditions, for 5 hours. The solution was then cooled to room temperature and the product of preparation 1 (10.5 g, 150 mmol) was added. The mixture was re-heated under reflux, using Dean and Stark conditions, for a further 8 hours. The reaction mixture was then allowed to cool to room temperature and was triturated with toluene (150 mL) to yield an orange coloured solid. The solid was filtered off and the filtrate was evaporated under reduced pressure to give a red oily residue. The residue was dissolved in dichloromethane (400 mL), washed with saturated sodium hydrogen carbonate solution (2×300 mL), dried over magnesium sulfate and concentrated in vacuo. Purification of the residue by column chromatography on silica gel, eluting with dichloromethane:methanol:0.88 ammonia, 97:3:0.2 to 93:7:0.7, followed by trituration with diethyl ether afforded the title product in 30% yield, 5.57 g.

1. temperaturethe solution was heated
2. additionwas added
3. temperatureThe mixture was re-heated
4. temperatureunder reflux
5. temperatureto cool to room temperature
6. customwas triturated with toluene (150 mL)
7. customto yield
8. filtrationThe solid was filtered off
9. customthe filtrate was evaporated under reduced pressure
10. customto give a red oily residue
11. washwashed with saturated sodium hydrogen carbonate solution (2×300 mL)
12. dry with materialdried over magnesium sulfate
13. concentrationconcentrated in vacuo
14. customPurification of the residue by column chromatography on silica gel
15. washeluting with dichloromethane

ORD 기록

ord-e080eb1b839941dd83e4cc3a072b04a4

출처 데이터셋

uspto-grants-2009_07

DOI

10.6084/m9.figshare.5104873.v1

특허 번호

US07557121B2