Scheme 1.

Synthesis of 5-fluoro cytidine phosphoramidites 5 and 9; (a) 12 eq. acetic anhydride (for 2) or benzoic anhydride (for 6) in anhydrous ethanol, room temperature, 14 h, 99% (2) and 99% (6); (b) 1.1 eq. 4,4′-dimethoxytrityl chloride in pyridine, room temperature, 14 h, 60% (3) and 56% (7); (c) 1.8 eq. silver nitrate, 1.8 eq. tert.-butyldimethylchlorosilane in tetrahydrofurane/pyridine, room temperature, 15 h, 48% (4a) and 58% (8a) (yields after separation from 4b and 8b, respectively); (d) 2 eq. (2-cyanoethyl)-N,N-diisopropylchlorophosphoramidite, 10 eq. N-ethyldiisopropylamine, 5 eq. 1-methylimidazole in dichloromethane, room temperature, 2.5 h, 58% (5) and 57% (9).