Thymidine → 5'-O-phthalimidothymidine

Participants

Reaction Steps

To a stirred solution of thymidine (24.22 g, 0.1 mol), N-hydroxyphthalimide (21.75 g, 0.13 mol), triphenylphosphine (34 g, 0.13 mol) in dry DMF (400 ml) was added diisopropylazodicarboxylate (30 ml, 0.15 mol) over a period of 3 h at 0° C. After complete addition the reaction mixture was warmed up to room temperature and stirred for 12 h. The solution was concentrated under vacuum (0.1 mm, <40° C.) to furnish an orange-red residue. The residual gum was washed several times with Et2O and washing were discarded. The semi-solid residue was suspended in EtOH (500 ml) and heated (90° C.) to dissolve the product. On cooling 30.98 g (80%) of 5′-O-phthalimidothymidine was collected in 3-crops as white crystalline material, mp 233-235° C. (decomp.); H NMR (DMSO-d6) δ 11.29 (s, 1, NH), 7.85 (m , 4, ArH), 7.58 (s, 1, C6H), 6.20 (t, 1, H1′, J1′,2′=7.8 Hz, J11′,2″=6.5 Hz), 5.48 (d, 1, OH3′), 4.36 (m, 3, H4′,5′,5″), 4.08 (m, 1, H3′), 2.09-2.13 (m, 2, H2′,2″), and 1.79 (s, 3, CH3). Anal. Calcd. for C18H17O7N3.0.7 H2O: C, 54.05; H, 4.64; N, 10.51. Found: C, 53.81; H, 4.25; N, 10.39.

Provenance & Evidence