The benzoylation of 2'-deoxy-5-iodouridine (I) with benzoyl chloride by means of pyridine in dichloromethane gives 5'-O-benzoyl-2'-deoxy-5-iodouridine (II), which is treated with benzyl trichloroacetimidate (III) and trifluoromethanesulfonic acid in dichloromethane - THF to afford the 3'-O-benzyl derivative (IV). The hydrolysis of (IV) with sodium ethoxide in ethanol yields 3'-O-benzyl-2'-deoxy-5-iodouridine (V), which is finally trifluoromethylated with bromotrifluoromethane and copper in pyridine-DMF by means of dimethylaminopyridine. The tritylation of 2'-deoxyuridine (IX) with trityl chloride in hot pyridine gives 2'-deoxy-5'-O-trityluridine (X), which is benzylated with benzyl chloride and NaH in THF yielding 3'-O-benzyl-2'-deoxy-5'-O-trityluridine (XI). The photochemical trifluoromethylation of (XI) with N-nitroso-N-(trifluoromethyl)trifluoromethanesulfonamide and biacetyl in acetonitrile irradiated with a high-pressure Hg lamp in a glass tube at room temperature affords 3'-O-benzyl-2'-deoxy-5-(trifluoromethyl-5'-O-trityluridine (XII), which is finally deprotected with HCl in methanol.
The benzoylation of 2'-deoxy-5-(trifluoromethyl)uridine (VI) with benzoyl chloride by means of triethylamine in dimethylacetamide gives 3-benzoyl-2'-deoxy-5-(trifluoromethyl)uridine (VII), which is benzylated with benzyl bromide and silver oxide in refluxing 2-butanone to afford 3-benzoyl-3'-O-benzyl-2'-deoxy-5-(trifluoromethyl)uridine (VIII). Finally, this compound is debenzoylated with 30% aqueous ammonia at room temperature. The deprotection of 2'-deoxy-3'-O-(thiobenzoyl)-5-(trifluoromethyl)-5'-O-trityluridine (XIII) with 0.1N HCl gives 2'-deoxy-3'-O-(thiobenzoyl)-5-(trifluoromethyl)uridine (XIV), which is submitted to desulfurization with Raney-Ni in THF.