3-Methyl-4H-[1,2,4]-oxadiazol-5-one: a versatile synthon for protecting monosubstituted acetamidines

The utilization of 3-methyl-4H-[1,2,4]-oxadiazol-5-one as a versatile protected acetamidine is demonstrated through employment in a variety of synthetic sequences. The potassium salt (2a) or the neutral form (2b) is alternatively shown to be superior for various synthetic reactions (i.e., alkylation, Michael addition, Mitsunobu) to incorporate side chains for further synthesis. The 3-methyl-4H-[1,2,4]-oxadiazol-5-one moiety was found to be stable to acid or base under non-aqueous conditions. It was also found to be stable to many reagents commonly used for organic synthesis. Despite this stability, the free acetamidine may be released by mild reduction including Lindlar hydrogenation or dissolving metal reductions. Alternatively, the hydroxyl amidine may be formed via alkaline hydrolysis.