According to the present invention, there is provided a process for making
an oligonucleotide or a phosphorothioate oligonucleotide. The process has
the following steps: (a) providing an amount of a blocked nucleotide; (b)
deblocking the blocked nucleotide to form an unblocked nucleotide; (c)
activating the deblocked nucleotide; (d) coupling the deblocked
nucleotide with a phosphoramidite to form a phosphite oligomer; (e)
capping any uncoupled deblocked nucleotide via reaction with an amount of
acetic anhydride and an amount of N-methylimidazole that is substantially
free of 1,3,5-trimethylhexahydro-1,3,5-triazine; (f) oxidizing the
phosphite oligomer to form the oligonucleotide or sulfurizing the
phosphite oligomer to form a phosphorothioate oligonucleotide; and (g)
optionally repeating steps (b) through (f). There is also a process for
capping a nucleotide.