Phosphonate-free phosphorylation of alcohols using bis-(tert-butyl) phosphoramidite with imidazole•hydrochloride and imidazole as the activator

A variety of commercially available alcohols were converted to their bis-(tert-butyl) protected monophosphate pro-drugs. The improved procedure uses the unique combination of imidazole center dot hydrochloride and imidazole as the activator to suppress the formation of undesired phosphonate by-product frequently encountered with the bis-(tert-butyl) phosphoramidite reagents. The new activation procedure eliminates the need to use excess reagents. (C) 2011 Elsevier Ltd. All rights reserved.