Preparation of resin-bound N-(alpha-methoxyalkyl)amides: An advantageous use of solid-phase chemistry for the handling of unstable precursors of the versatile N-acyliminium ions

The development of a new and efficient synthesis of resin-bound N-(alpha -m ethoxyalkyl)amides is described. The condensation of aldehydes on a support ed amide in the presence of trimethyl orthoformate afforded, in acidic medi a, the resin-bound N-acyliminium ion precursors. Repeating the reaction a s econd time led to a great improvement in yields, demonstrating one advantag e of the solid-phase chemistry for the handling of sensitive intermediates difficult to isolate.