Scheme 2.

Synthesis of 2′-SCF₃ adenosine phosphoramidite A9. Reaction conditions: a) 3.0 equiv N,N-di-n-butylformamide dimethyl acetal, in DMF, RT, 26 h, 96 %; b) 1.5 equiv F₃CSO₂Cl, 3.0 equiv DMAP, in CH₂Cl₂, 0 °C, 20 min; c) 1.5 equiv CH₃COS⁻K⁺, 1.5 equiv 18-crown-6, in toluene, 17 h, 45 °C, 93 % (over two steps); d) 0.1 M NaOH, in EtOH/pyridine/H₂O (20:20:1), 0 °C, 10 min, 75 %; e) 1.2 equiv 3,3-dimethyl-1-(trifluoromethyl)-1,2-benziodoxole, in CH₂Cl₂, −78 °C to RT, 16 h, 85 %; f) 1 M TBAF, 0.5 M CH₃COOH, in THF, RT, 1.0 h, 72 %; g) 1.1 equiv DMT-Cl, 0.1 equiv DMAP, in pyridine, RT, 14 h, 87 %; h) 1.5 equiv 2-cyanoethyl N,N-diisopropylchlorophosphoramidite, 10 equiv CH₃CH₂N(CH₃)₂, CH₂Cl₂, RT, 3 h, 73 %.