Reaction Steps
A mixture of 6-chloroinosine (4, 32.5 g, 113 mmol) and the acetal linker 3 (47.5 g, 147 mmol) was dissolved in DMF (230 mL). p-Toluenesulfonic acid monohydrate (1.1 g, 5.7 mmol) was added, and the solution was placed on a Buechi R-134 rotavapor and agitated under reduced pressure (70 mbar) at 50° C. for 15 h. The solvent was removed in vacuo, the resulting residue was dissolved in EtOAc (1 L) and neutralized with triethyl amine (0.8 mL, 5.7 mmol). The solution was then washed with saturated aqueous NaCl (3×1 L), H2O (1 L), dried (MgSO4), filtered and concentrated. The resulting residue was taken up in EtOAc and triturated with hexanes, upon which the product precipitated as a white powder (5, 59.3 g, 109 mmol, 96%, mixture of two diastereomers): M.p.: 103-105° C.; 1H-NMR (400 MHz, CDCl3) δ=8.78 (s, 1H), 8.77 (s, 1H′), 8.41 (s, 1H), 8.33 (s, 1H′), 7.47 (d, J=8.6 ,2H), 7.37 (d, J=8.6, 2H′), 6.95 (d, J=8.5, 2H), 6.89 (d, J=8.5, 2H′), 6.24 (s, 1H), 6.19 (m, 1H, 1H′), 6.02 (s, 1H′), 5.91 (m, 1H, 1H′), 5.37-5.18 (m, 4H, 4H′), 4.77 (m, 1H, 1H′), 4.72 (s, 1H, 1H′), 4.58 (m, 2H, 2H′), 4.04-3.85 (m, 4H, 4H′), 2.37 (m, 2H, 2H′), 1.81 (m, 2H, 2H′), 1.71 (m, 2H, 2H′), 1.52 (m, 2H, 2H′); 13C -NMR (400 MHz, CDCl3) δ=173.4, 173.4, 160.5, 160.4, 152.0, 151.8, 150.8, 150.7, 132.8, 132.6, 132.3, 132.3, 132.1, 132.1, 128.2 (2C), 128.0 (2C), 127.5, 127.5, 118.3, 118.3, 114.8, 114.8, 114.6 (2C), 114.6 (2C), 108.0, 104.9, 93.5, 91.6, 86.4, 86.4, 84.3, 83.8, 83.3, 80.5, 67.9, 67.8, 65.1, 65.1, 63.2, 62.9, 34.2, 34.2, 28.9, 28.9, 25.7, 25.7, 24.7, 24.7; IR (film) ν=3233, 3109, 3073, 2934, 1727, 1595, 1396, 1245, 1194, 1167, 1101, 1073, 984, 832; HRMS (MALDI-FTMS) m/z 567.1627(567.1617 calculated for C26H29N4O7ClNa (M+Na)+).
