The formation of an unexpected heterocyclic scaffold, a benzoxazole, in a three-component reaction between a ketone, isocyanide, and 2-aminophenol was encountered. This reaction involved a benzo[b][1,4]oxazine intermediate resulting from intramolecular attack of the aminophenol hydroxyl group on the nitrilium ion. Unlike previous literature examples, the trapped nitrilium benzo[b][1,4]oxazine could readily be subjected to ring opening with bis-nucleophiles. The reaction scope includes simple linear as well as complex cyclic ketones and substituted 2-aminophenols. A representative benzoxazole product could be further diversified to yield drug-like compounds.