Pyruvic acid Quinine

The first successful syntheses of quininic acid (CXXXVII, R = OCHt) were achieved independently in 1912 by Kaufmann and Peyer (183), and Pictet and Misner (184). The former group applied to 6-methoxy-quinoline the method which they had used earlier in the synthesis of cinchoninic acid from quinoline. Pictet and Misner isolated ethyl quininate in small yield directly from the condensation of p-anisidine with formaldehyde and pyruvic acid in the presence of hydrochloric acid. 

Numerous other methods for the syntheds of the methoxy acid were developed subsequently. The pyruvic acid-isatin condensation, and the Thielepape synthesis, were extended by the use of appropriately meth-oxylated starting materials (185, 186). The transformation of m-cresol into quininic acid has been reported by Koelsch (187). In 1931 Rabe and co-workers (188, 189) condensed p-anisidine with acetoacetic ester and obtained a product, which on cyclization with 90% sulfuric acid gave... 

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