A Preferred Synthesis of 1,2,4‐Oxadiazoles

Abstract

An efficient and high‐yielding one‐pot synthesis of 1,2,4‐oxadiazoles from carboxylic acids and amidoximes is described. Activation of the carboxylic acid using hydroxybenzotriazole (HOBt) and EDC/HCl followed by reaction with an amidoxime generates an oxime ester. Without isolation, the oxime ester is dehydrated to give the oxadiazole ring.

Keywords:

• 1,2,4‐Oxadiazoles
• Carboxylic acids
• Hydroxybenzotriazole
• High‐yielding synthesis

Acknowledgments

We thank Dr. Raymond Cvetovich and Dr. E.J.J. Grabowski for helpful discussions. Thanks to Lisa DiMichele and Bob Reamer for NMR confirmations and Mirlinda Biba for SFC chiral separations for the oxadiazoles prepared from serine.

Notes

^aA Soxhlet apparatus was not as efficient in water removal.