Allyl bromide → 3'-O-Allyl-5'-O-(tert-butyldimethylsilyl)-5-iodo-2'-deoxycytidine

Participants

Reaction Steps

To a solution of NaH (60%, 113 mg, 2.84 mmol) in THF (26 ml) under N2 atmosphere, was slowly added a solution of the starting nucleoside (39) (669 mg, 1.43 mmol) in THF (6 ml). The mixture was stirred at room temperature for 45 minutes, cooled at 0° C. and allyl bromide (134 μL, 1.58 mmol) was slowly added. After 15 h at room temperature, the solution was cooled to 0° C. and quenched by addition of H2O (5 ml). THF evaporated under reduced pressure and the product extracted into EtOAc (3×25 ml). Combined organic extracts were dried (MgSO4) filtered and the volatiles evaporated under reduced pressure to give a residue that was purified by flash chromatography on silica gel with EtOAc affording the expected 3′-O-allyl product (40) (323 mg, 44%) as a colourless oil, together with some unreacted starting material (170 mg); 1H NMR (d6 DMSO) δ 0.00 (s, 3H, CH3), 0.01 (s, 3H, CH3), 0.79 (s, 9H, 3CH3), 1.84 (ddd, J=13.3, 8.2 and 5.5 Hz, 1H, H-2′), 2.20-2.25 (m, 1H, H-2′), 3.62-3.72 (m, 2H, H-5′), 3.88-3.93 (m, 4H, H-3′,4′, HHC—CH═), 5.1 (dd, J=8.5, 1.7 Hz, 1H, CH═CHH), 5.16 (dd, J=17.2, 1.7 Hz, 1H, CH═CHH), 5.75-5.83 (m, 1H, CH═CHH), 5.94 (dd, J=8.4, 5.6 Hz, 1H, H-1′), 6.53 (br s, 1H, NHH), 7.74 (br s, 1H, NHH), 7.83 (s, 1H, H-6); MS (ES): m/z (%) (M−H) 506 (100%).

Provenance & Evidence