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

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Reaction Steps

2′-Deoxycytidine (5.82 g, 25.6 mmol) was dried by evaporation with dry pyridine (2′50 mL) and taken up in dry pyridine (100 mL). To this suspension, trimethylsilyl chloride (11.5 mL, 90.6 mmol) was added and the mixture was stirred at ambient temperature for 2 hours. The reaction mixture was cooled using an ice water bath and benzoyl chloride (4.60 mL, 39.6 mmol) was slowly introduced. The ice-water bath was removed and the mixture was stirred at room temperature for an additional 2 hours. The reaction was quenched by adding methanol (15 mL), concentrated to one half of the original volume and filtered. To the filtrate, water (30 mL) was added and the solution was evaporated to an oil. Additional evaporations with water (3×30 mL) were performed to remove pyridine, and the resulting residue was partitioned between water and ethyl acetate. After vigorous stirring, the product crystallized from the aqueous layer. The crystals were washed with cold water and ethyl acetate, and they were used in the next step without further purification. TLC: Rf(B)=0.7. Crude N4-benzoyl-2′-deoxycytidine was dried by evaporation with dry pyridine (3×50 mL), and then dissolved in the same solvent (100 mL). 4,4′-Dimethoxy-tritylchloride (7.4 g, 22 mmol) was added portion-wise to the reaction mixture, and the stirring was continued overnight at ambient temperature. The reaction mixture was evaporated to an oil and dissolved in CH2Cl2 (100 mL). The organic phase was washed with saturated aqueous NaHCO3 (50 mL) and water (3×100 mL), and dried with anhydrous Na2SO4. After coevaporation with toluene, the residue was applied onto a silica gel column and eluted with a gradient of MeOH in CH2Cl2 (0-8% MeOH). The title compound (6) was obtained in 65% yield (9.0 g) starting from 2′-deoxycytidine.

Provenance & Evidence