Carbon Dioxide → 2',5'-Dimethoxy-2-(2-piperidyl)acetophenone

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Reaction Conditions

Reaction Steps

Magnesium methyl carbonate (approximately 1 mole of a 2 M solution in dimethylformamide) is heated to 120°C. under an atmosphere of carbon dioxide and 45.0 g (0.25 mole) of 2',5'-dimethoxyacetophenone added thereto. Nitrogen is substituted for the carbon dioxide and the mixture is stirred at 120°C. for 5 hours while allowing the methanol that forms to escape. The mixture is cooled under carbon dioxide and 25.3 g (0.30 mole) of 2,3,4,5-tetrahydropyridine (as the trimer, α-tripiperidein) added. The resulting mixture is stirred at room temperature in an atmosphere of carbon dioxide for 40 hours, poured into 3 liters of ethyl ether and the resulting precipitate is collected by filtration. The filtrate is acidified with a mixture of 300 ml of concentrated HCl-ice and the resulting precipitate is collected by filtration. The filtrate is made alkaline with 2N NaOH, extracted with ethyl ether, the extracts dried (Na2SO4) and the solvent removed. The resulting oily residue is converted to the hydrochloride salt by the addition of isopropanolic HCl. The two portions are combined and recrystallized from isopropanolwater to yield 56.0 g (75% of theory) of 2',5'-dimethoxy-2-(2-piperidyl)acetophenone as the hydrochloride salt having a M.P. of 186°-188°C. (dec.)

Provenance & Evidence