Thionyl Chloride → 4-Pyridinecarboxylic acid, 3-(chlorocarbonyl)-, methyl ester

Beteiligte Stoffe

Reaktionsschritte

Following the procedure of Example 30, 4-methoxycarbonylnicotinic acid is reacted with thionyl chloride to give 4-methoxycarbonylnicotinoyl chloride. A slurry of the above chloride (22.7 mmol) in 100 ml of monoglyme (ethylene glycol dimethyl ether) is added to a chilled mixture of the sodium salt of diethyl malonate (2.2 eq.) in monoglyme. The mixture is allowed to warm to RT and is stirred at RT for 4 hours. Aq. sodium bicarbonate is added and the mixture is extracted with ether. It is then acidified to pH 2-3 and again extracted with ether. The combined organic phases of the acid layer are dried, filtered and concentrated to give methyl 3-(diethyl malonylcarbonyl)isonicotinate, which is then reacted with lithium hydroxide monohydrate and then hydrochloric acid to give 3-acetylisonicotinic acid.

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