Sulfuric acid magnesium salt (1:1) → Ethyl 2-(Trifluoromethyl)-7-(triphenylmethyl)-5,6,7,8-tetrahydro-1,7-naphthyridine-3-carboxylate

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Reaction Steps

A mixture of N-trityl-3-piperidone (1.22 g, 3.6 mmol), magnesium sulfate (2.70 g) and pyrrolidine (0.36 mL, 4.3 mmol) in 10 mL of tetrahydrofuran was stirred at room temperature for 72 h. The reaction mixture was filtered, and the filtrate was concentrated under reduced pressure. The resultant crude enamine was dissolved in 15 mL of dry dioxane, cooled to approximately 10° C. and treated dropwise with ethyl 2-(ethoxymethylene)-4,4,4-trifluoro-3-oxobutyrate (0.77 mL, 3.9 mmol). The resultant red-orange solution was allowed to warm to room temperature overnight. Ammonium acetate (0.61 g) was added to the blood-red solution, and the mixture was heated at reflux for 3 h, cooled to room temperature and concentrated under reduced pressure. The residue was stirred with 100 mL of dry ether, filtered through a pad of Celite, and concentrated under reduced pressure. The resultant dark red gum was purified by flash chromatography (silica gel; 5% ethyl acetate/hexanes as eluant) to afford the title compound as a light orange foam.

Provenance & Evidence