Methyl vinyl ketone → 3-Pyridinepropanoic acid,6-methyl-b-oxo-a-(3-oxobutyl)-,ethyl ester

Participants

Reaction Conditions

Reaction Steps

To a stirred solution containing 48 g. of ethyl 3-(2-methyl-5-pyridinyl)-3-oxopropanoate in a mixture of 300 ml. of dry benzene and 100 ml. of dry methanol, said solution kept under nitrogen, was added 0.1 g. of sodium methoxide followed by the dropwise addition over a period of about one hour of the solution containing 16 g. of freshly distilled methyl vinyl ketone in a mixture of 60 ml. of benzene and 10 ml. of methanol. After the reaction had proceeded slowly at room temperature overnight, an additional 0.1 g. of sodium methoxide plus 4 ml. of additional methyl vinyl ketone were added and the reaction mixture was heated with stirring at 40° C. for eight hours. The solvent was distilled-off in vacuo; 300 ml. of benzene was added; the benzene solution was washed once with brine, dried over anhydrous sodium sulfate and heated in vacuo to remove the benzene thereby yielding a quantative yield (63.5 g.) of ethyl 2-(2-methyl-5-pyridinylcarbonyl)-5-oxohexanoate which was added to a mixture containing 95 ml. of concentrated sulfuric acid and 185 ml. of water. The acidic reaction mixture was slowly heated. After about thirty minutes, the temperature reached 55° C. and the evolution of carbon dioxide became noticeable. The temperature of the reaction mixture was maintained at 65° C. for about one hour and then heated to 80° C. and held there for several minutes. By this time the evolution of carbon dioxide appeared to be over. The reaction mixture was cooled and poured into a solution of 305 g. of potassium carbonate in 1 liter of ice water. Chloroform was added; the mixture was shaken well and filtered to remove the precipitated potassium sulfate; and, the layers were separated. The aqueous layer was extracted further with chloroform; the combined chloroform extracts were dried over anhydrous sodium sulfate and filtered; the dried filtrate was heated in vacuo to remove the chloroform to yield, after air-drying, 27.4 g. (80%) of 1-(2-methyl-5-pyridinyl)hexan-1,5-dione, a tan solid melting at 85°-87° C.

Provenance & Evidence