Some derivatives of salicylic acid containing substituents meta to the carboxyl group were used to prepare analogs of the anticoagulant drug warfarin, 3‐(1‐phenyl‐3‐oxobutyl)‐4‐hydroxycoumarin, containing substituents in either the 6‐or 8‐position of the courmarin ring. When the substituent was the hydroxyl group, the resulting products are previously identified metabolites of warfarin. The substituted salicylic acid is first acetylated with acetic anhydride, then either converted to the acid chloride and condensed with diethyl malonate in the presence of sodium hydroxide or converted to the mixed anhydride with formic acid and condensed with ethoxymagnesium diethyl malonate to yield, in either case, the corresponding 3‐carbethoxy‐4‐hydroxycoumarin substituted in the 6‐ or 8‐position of the coumarin ring. These compounds readily condense with benzalacetone to form the corresponding substituted warfarin in the presence of 5 mole % tertiary amine catalyst. This method offers an improved route for the synthesis of 8‐hydroxywarfarin.

Aus 2,3‐Dihydroxy‐benzoesäure (Ia) erhält man über das Diacetat (Ib) das Säurechlorid (II), das mit Malonester zu dem Cumarin (III) cyclisiert.