Preparation of Resin-Bound N-(-Methoxyalkyl)amides: An Advantageous Use of Solid-Phase Chemistry for the Handling of Unstable Precursors of the Versatile N-Acyliminium Ions

Abstract

The development of a new and efficient synthesis of resin-bound N-(α-methoxyalkyl)amides is described. The condensation of aldehydes on a supported amide in the presence of trimethyl orthoformate afforded, in acidic media, the resin-bound N-acyliminium ion precursors. Repeating the reaction a second time led to a great improvement in yields, demonstrating one advantage of the solid-phase chemistry for the handling of sensitive intermediates difficult to isolate.