GENERAL STEPS: To an anhydrous N,N-dimethylformamide (DMF, 70 mL) solution of 5-iodo-2'-deoxyuridine (5.0 g, 14 mmol) was added imidazole (1.09 g, 16 mmol), followed by tert-butyldimethylsilyl chloride (TBDMSCl, 2.41 g, 16 mmol) at 0 °C. The reaction mixture was placed in an ice bath and stirred overnight. Upon completion of the reaction, it was quenched with saturated aqueous NaHCO3 and washed with aqueous NaCl followed by extraction with ethyl acetate (EtOAc). The organic layer was dried over anhydrous magnesium sulfate (MgSO4) and concentrated under reduced pressure to remove the solvent. The crude product was purified by silica gel column chromatography (eluent: EtOAc/petroleum ether, 3:7, v/v) to afford the target product 1-((2R,4S,5R)-5-(((tert-butyldimethylsilyl)oxy)methyl)-4-hydroxytetrahydrofuran-2-yl)-5-iodopyrimidine-2,4(1H,3H)-dione (5.9 g, 90% yield) as colorless solid. 1H NMR (d6-DMSO) δ: 0.00 (s, 3H, CH3), 0.79 (s, 9H, tBu), 1.88-1.97 (m, 1H, H-2'), 2.00-2.05 (m, 1H, H-2'), 3.59-3.71 (m, 2H, H-5'), 3.75 (br s, 1H, H-4'), 4.06 (br s, 1H, H-3'), 5.18 (d, J = 4.0 Hz, 1H, OH), 5.98 (t, J = 5.9 Hz, 1H, H-1'), 7.89 (s, 1H, H-6), 11.62 (s, 1H, NH). MS (negative electrospray): calculated value C15H25IN2O5Si [M-H]- 468.06, measured value 467.
