N4-Benzoyl-3'-O-(4,4'-dimethoxytrityl)-2'-deoxycytidine → N-Benzoyl-5'-O-(4,4'-dimethoxytrityl)-2'-deoxycytidine

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To a solution of N4-benzoyl-2′-deoxycytidine (119.0 g) in pyridine (1.5 L), 4, 4′-dimethoxytritylchloride (113.5 g) was added over two hours and the mixture was stirred at room temperature for a further four hours. Sodium hydrogencarbonate (33.8 g) was added and stirred for two hours, and then the reaction solution was condensed. Ethyl acetate (1.2 L) and water (300 mL) were added to the residue and the mixture was stirred. A small amount of saturated saline solution was added to the mixture and the resultant liquid was separated. The extracted organic layer was washed with water, and dried with anhydrous magnesium sulfate. The mixture was filtered and then the solvent was removed. The residue was purified by silica gel column chromatography with ethyl acetate as a solvent. A fraction including the target substance was added dropwise to diisopropyl ether (2.0 L) with vigorous stirring, and then the resultant mixture was stirred at room temperature for two hours. The filtrate was dried in a vacuum at 50° C. to yield non-hydrated N4-benzoyl-5′-O-(4, 4′-dimethoxytrityl)-2′-deoxycytidine (153.3 g). The XRD pattern showed that the free product was amorphous. Furthermore, the component contained N4-benzoyl-2-deoxycytidine, which was the raw material, N4-benzoyl-3′-O-(4, 4′-dimethoxytrityl)-2′-deoxycytidine, and N4-benzoyl-3′, 5′-O-bis(4, 4′-dimethoxytrityl)-2′-deoxycytidine, both of which were byproducts, and the rates of the respective peak areas were 1.0%, 0.15%, and 2.2%, respectively.

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