afford an exocyclic enol ether, from which the second morpholine ring is constructed in two steps. Attempted formation of a 6-methyl-substituted morpholine enol ether led to the unexpected formation of its 5-methyl regioisomer. The use of super-stoichiometric quantities of acid suppressed this pathway, which we postulate prevents the formation of aziridinium intermediates that we propose is the source of the regioisomer. The overall synthesis is high-yielding and can be performed on large scale from readily available starting materials. The method can be extended to the generation of 6,7-and 7,7-spiroacetal analogues, and to substituted 6,6-systems although this introduces issues of diastereoselectivity, which in some instances can be improved by acid-mediated anomerization. The two amine functionalities embedded in the 6,6-and 6,7-spiroacetal scaffolds can be sequentially functionalized, providing entry into compound libraries that occupy drug-like chemical space. These spiroacetals are hydrolytically stable and therefore represent attractive starting materials for drug discovery.