5-aryl -4-oxazolecarboxylic acid

In a model study, Helquist and co-workers described the reaction of dimethyl diazomalonate 128 with benzonitrile to prepare 5-methoxy-2-phenyl-4-oxazolecar-boxylic acid methyl ester 129 nearly quantitatively (Scheme 1.35). Several other 2-aryl-5-methoxy-4-oxazolecarboxylic acid methyl esters were prepared analogously. In addition, 2-aIkyl(aIkenyl)-5-methoxy-4-oxazolecarboxylic acid methyl esters were also prepared, although the yields for aliphatic nitriles were not as good, unless the nitrile was used as solvent. Other metal salts—including Rh2 (NHAc)4, Cu(OTf)2, Cu(C2Hs-acac)2, Rh2(02CC3H7)4, and Rh3(CO)ie— were not as effective as Rh2(OAc)4 in this reaction. 

Ozaki and co-workers prepared an extensive series of 5-aryl(heteroaryl)-4-oxazolecarboxylic acid methyl esters 368 (20 compounds) from acylation of methyl isocyanoacetate, followed by in situ cyclization (Scheme 1.100). These compounds were elaborated further and evaluated as blood platelet aggregation inhibitors. 

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