2'-Deoxy-2-fluoroadenosine → 5'-O-(4,4'-Dimethoxytrityl)-2'-deoxy-2-fluoroadenosine

Participants

Reaction Steps

2′-deoxy-2-fluoroadenosine (20, 12 g, 0.45 mol) and dimethoxytrityl chloride (18.1 g, 0.53 mol) were dissolved in anhydrous pyridine (100 mL) and stirred at ambient temperature until the trace amount of the starting material remaining matched the bis DMT impurity forming (3 h) as monitored by TLC (Rf 0.20, starting material; Rf 0.60, product; Rf 0.85, bis DMT product, ethyl acetate-methanol 9:1). The reaction was quenched by the addition of methanol (50 mL) and then concentrated under reduced pressure to an oil. The residue was partitioned between ethyl acetate (250 mL) and sat'd sodium bicarbonate (250 mL). The aqueous layer was extracted with ethyl acetate (100 mL) once more and the combined extracts were concentrated under reduced pressure. The resulting oil was purified by silica gel chromatography (400 g) using a gradient of methanol in ethyl acetate (0-5%). The appropriate fractions were combined, concentrated under reduced pressure, coevaporated with anhydrous acetonitrile (200 mL) and dried (1 mm Hg, 25° C., 24 h) to a foam, 23.2 g (90%). The product can be crystallized from dichloromethane to give white crystals, mp 239-243° C. H-NMR (DMSO-d6) d 2.2-2.4 and 2.7-2.9 (m, 2, 2′-CH2), 3.18 (m, 2, 5′-H and 5″-H), 3.75 (s, 6, O—CH3), 3.98 (m, 1, 4′-H), 4.43 (m, 1, 3′-H), 5.38 (d, 1, 3′-OH), 6.15 (t, 1, 1′-H), 6.83 (m, 4, arom.), 7.15-7.4 (m, 9, arom.), 7.83 (br s, 2, NH2), 8.23 (s, 1, 8-H). F-NMR (DMSO-d6) δ-53.5 (s).

Provenance & Evidence