Method of preparing oligomeric compounds using modified coupling protocols

A method of coupling solid support bound free hydroxyl groups to bicyclic nucleosides of Formula I:

• wherein for each bicyclic nucleoside of Formula I:
• Bx is an optionally protected heterocyclic base moiety;
• T1 is a hydroxyl protecting group;
• T2 is a reactive phosphorus group capable of forming an internucleoside linkage;
• one of Q1 and Q2 is H and the other of Q1 and Q2 is C1-C6 alkyl or substituted C1-C6 alkyl where each substituted group is OJ1, SJ1, NJ1J2, N3 or CN wherein each J1 and J2 is, independently, H or C1-C6 alkyl;
• comprising treatment of the free hydroxyl groups with a coupling reagent which is about 70% by volume activator solution consisting of 1.0 molar 4,5-dicyanoimidazole and about 0.1 molar N-methylimidazole in acetonitrile and about 30% by volume of a solution having about a 0.2 molar concentration of bicyclic nucleosides of Formula I disolved in acetonitrile or a mixture of acetonitrile and toluene and wherein the volume of coupling reagent added provides about 1.75 equivalents of bicyclic nucleosides of Formula I based on the initial loading of the solid support with free hydroxyl groups.