Water → N6-monomethoxytrityideoxyadenosine

Participants

Reaction Steps

Deoxyadenosine hydrate dA×H2O (50 g, 186 mmol.) was dried by coevaporation with pyridine and acetonitrile, and suspended in acetonitrile (200 ml). 1,1,1,3,3,3-hexamethyldisilazane (96 ml, 74.9 g, 465 mmol) was added and the resulting suspension was stirred over night at ambient temperature. The reaction mixture was concentrated to dryness by evaporation. The residue was dried by coevaporation with pyridine and dissolved in pyridine (260 ml). The solution was cooled on an ice bath and monomethoxytritylchloride (54.5 g, 177 mmol) was added. The reaction mixture was kept in a refrigerator at appr. 4° C. for 3 days. Additional portions of monomethoxytritylchloride (2 times 13.6 g, 45 mmol) were added successively in 24-hour time intervals while the reaction mixture was stirred at ambient temperature. The reaction mixture was treated with N-methylmorpholine (30 ml), stirred at ambient temperature for 30 minutes and evaporated to dryness. The residue was dissolved in ethylacetate (330 ml) and extracted with water (200 ml), 5% aqueous sodium hydrogencarbonate solution (2 times 200 ml) and brine (200 ml). The organic phase was concentrated to dryness by evaporation. The residue was dissolved in pyridine (100 ml) and water (20 ml), and stirred at 40° C. for 2 days. The solution was concentrated to a foam by evaporation. Purification by column chromatography on silica gel (acetone/dichloromethane, gradient elution) afforded the product in 99.9% purity by RP-HPLC (70 g, 67%). UV λmax 272 nm.

Provenance & Evidence