Thymidine → 5'-O-tert-Butyldimethylsilylthymidine

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Reaction Steps

5'-O-tert-Butyldimethylsilylthymidine (Compound 2, Table I) was prepared by dissolving thymidine (25 g, 0.10 mole), 4-N,N-dimethylaminopyridine (3.15 g, 0.026 mole) and triethylamine (13.5 g, 18.6 ml, 0.13 mole) in 200 ml of dry N,N-dimethylformamide under a stream of argon. 19.4 g (0.13 mol) tert-butyldimethylchlorosilane was added to the dissolved mixture, with the entire mixture then being stirred for six hours before evaporation of the solvent. The resulting gum was dissolved in 30 ml ethyl acetate and the solution extracted with 10 ml saturated sodium bicarbonate solution, 30 ml water and 30 ml brine. Following drying of the organic layer, the residue was purified by flash chromatography using dichloromethane/ethanol (50/1) as eluent. Evaporation of the product-containing fractions yielded 31.5 g of the desired 5'-O-tert-butyldimethylsilylthymidine as a white foam (86% yield).

Provenance & Evidence