Patent ID: 7019127

Claim:
In an improved process for the synthesis of a deprotected oligonucleotide, said process comprising assembling a protected phosphorothioate triester oligonucleotide, deprotecting the phosphorothioate triester oligonucleotide to form a deprotected phosphodiester oligonucleotide, deprotected phosphorothioate oligonucleotide, or a deprotected oligonucleotide comprising both phosphodiester and phosphorothioate diester internucleotide linkages, the improvement being that said assembling comprises solution phase coupling, in the presence of a coupling agent, (i) a protected nucleoside or oligonucleotide H-phosphonate comprising a 3′- or 5′H-phosphonate function; with (ii) a protected nucleoside or oligonucleotide comprising a free 3′- or 5′-hydroxy function; to form an H-phosphonate diester and, in situ, reacting the H-phosphonate diester with a sulfur transfer agent to produce said phosphorothioate triester.