4-Nitrophenol → 2'-O-(2-Methoxyethyl)-cytidine

Temperature

0 °C

2′-O-(2-Methoxyethyl)uridine (6.05 g, 20.0 mmol), 1-methylpyrrolidine (20 ml, 0.192 mol), chlorotrimethylsilane (7.6 ml, 59.9 mmol) and dry acetonitrile (100 ml) were stirred together at room temperature. After 1 hour, the reactants were cooled to 0° C. (ice-water bath) and trifluoroacetic anhydride (7.1 ml, 50.3 mmol) was added dropwise over 5 minutes. After a further period of 30 minutes at 0° C., 4-nitrophenol (8.35 g, 60 mmol) was added to the stirred reactants which were maintained at 0° C. After 3 hours, the products were poured into saturated aqueous sodium hydrogencarbonate (200 ml), and the resulting mixture was extracted with dichloromethane (3×100 ml). The combined organic layers were dried (MgSO4), and evaporated under reduced pressure. Concentrated aqueous ammonia (d 0.88, 20 ml) was added to a stirred solution of the residue in dioxane (100 ml), contained in a sealed flask that was then heated at 55° C. for 24 hours. The resulting yellow solution was concentrated under reduced pressure, and the residue was evaporated with absolute ethanol (3×50 ml). The products were fractionated by short column chromatography on silica gel: the appropriate fractions, which were eluted with dichloromethane-methanol-triethylamine (93:7:0.5 to 90:10:0.5 v/v) were evaporated under the reduced pressure to give the title compound as an off-white solid (5.07 g 84%).

1. additionwas added dropwise over 5 minutes
2. waitAfter a further period of 30 minutes at 0° C.
3. waitAfter 3 hours
4. extractionthe resulting mixture was extracted with dichloromethane (3×100 ml)
5. dry with materialThe combined organic layers were dried (MgSO4)
6. customevaporated under reduced pressure
7. additionConcentrated aqueous ammonia (d 0.88, 20 ml) was added to a stirred solution of the residue in dioxane (100 ml)
8. customcontained in a sealed flask
9. temperaturethat was then heated at 55° C. for 24 hours
10. concentrationThe resulting yellow solution was concentrated under reduced pressure
11. customthe residue was evaporated with absolute ethanol (3×50 ml)
12. washthe appropriate fractions, which were eluted with dichloromethane-methanol-triethylamine (93:7:0.5 to 90:10:0.5 v/v)
13. customwere evaporated under the reduced pressure

ORD record

ord-41a27e643249413bbae685e7207f4bc9

Source dataset

uspto-grants-2005_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06884881B1