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

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Reaction Steps

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.

Provenance & Evidence