Hydrogen Cyanide → 2-Ethyloxazole-5-carboxylic acid

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Reaction Steps

If one is unable to obtain 5-formyloxazole from commercial sources, one may prepare the compound under the procedure disclosed by J. Ratusky and F. Sorm, Chem. Listy, 51, 1091 (1957), or by following the steps in Scheme III. In the first step of Scheme III, an equimolar mixture of ethyl oxalyl chloride (which is commercially available, e.g., from Aldrich Chemical Co.), diazomethane, and triethylamine in diethyl ether is allowed to react at 20° C. for 4 hours to produce ethyl 2-oxo-3-diazopropionate (15). In the second step, the 2-oxo-3-diazopropionate (15) is pyrolyzed in the presence of hydrogen cyanide to generate a carbene intermediate, which then adds to the cyanide in a 1,3-dipolar addition. For example, 2-oxo-3-diazopropionate is heated at 80°-100° C. in digylme in the presence of a catalytic amount of copper powder. After a few minutes, an equimolar amount of hydrogen cyanide is slowly bubbled into the solution, and hating continued for an additional three hours. The product is isolated and purified by conventional means to yield ethyl 5-carboxyoxazole (16). The ethyl 5-carboxyoxazole is converted to 5-formyloxazole in the same manner as ethyl 4-carboxyoxazole (12) is converted to 4-formyloxazole (see Scheme II, steps 5-7).

Provenance & Evidence