Abstract
A simple and efficient method has been developed for the synthesis of substituted
morpholines by a sequence of coupling, cyclization, and reduction reactions of easily
available amino alcohols and α-halo acid chlorides. Various mono-, di-, and trisubstituted
morpholines, spiro morpholines, and ring-fused morpholines, as well as morpholine
homologues, were synthesized in good to excellent yields by a single methodology under
similar reaction conditions. The method was also used in a multigram synthesis of
(3S)-3-methylmorpholine.
Key words
morpholines - amides - cyclizations - coupling - reductions
