Method of synthesis of morpholino oligomers

A method of synthesizing a morpholino oligomer, the method comprising:

• (a) reacting a solid-phase-supported morpholino subunit comprising an unprotected morpholino ring nitrogen with a first morpholino subunit monomer comprising a triarylmethyl-protected morpholino ring nitrogen and an activated phosphoramidate group on a 5′-exocyclic carbon, thereby forming a phosphorodiamidate linkage between the 5′-exocyclic carbon of the first morpholino subunit monomer and the unprotected morpholino ring nitrogen of the solid-phase supported morpholino subunit monomer;
• (b) deprotecting the triarylmethyl-protected morpholino ring nitrogen, to form a product comprising an unprotected morpholino ring nitrogen;
• (c) optionally reacting the product from step (b) with a further morpholino subunit monomer comprising a triarylmethyl-protected morpholino ring nitrogen and an activated phosphoramidate group on a 5′-exocyclic carbon, thereby forming a phosphorodiamidate linkage between the 5′-exocyclic carbon of the further morpholino subunit monomer and the unprotected morpholino ring nitrogen of the product from step (b);
• and
• (d) optionally repeating steps (b) and (c) one or more times;
• wherein the deprotecting comprises exposing the triarylmethyl-protected ring nitrogen to a reagent solution comprising a heterocyclic amine salt in a trifluoroethanol-containing solvent, the salt being a salt of a heterocyclic amine with a sulfonic acid, trifluoroacetic acid or hydrochloric acid and having a pKa in the range of 1-4 in its protonated form.