Imidazole → 1-[(2R,4S,5R)-4-[tert-butyl(dimethyl)silyl]oxy-5-(hydroxymethyl)oxolan-2-yl]pyrimidine-2,4-dione

Temperatur

80 °C

To a solution of 2'-deoxyuridine (5.00 g, 22 mmol) in pyridine (20 ml) was added triphenylmethyl chloride (6.72 g, 24 mmol) and dimethylaminopyridine (0.20 g, 1.6 mmol). The mixture was allowed to stir at 80° C. for 30 min. The pyridine was removed under reduced pressure and the residue dissolved in DMF (30 ml). Imidazole (3.59 g, 53 mmol) and t-butyldimethylsilyl chloride (3.92 g, 26 mmol) were added, and the mixture was allowed to stir overnight at room temperature. The DMF was removed under reduced pressure, and the residue was dissolved in 80% aqueous acetic acid (20 ml). The mixture was allowed to reflux for 30 min, cooled, and neutralized with NaOH. The mixture was lyophilized, and the residue was purified by chromatography (1:1 EtOAc: hexanes) to give 22 as a white solid (3.13 g, 9.14 mmol, 41.51% yield): mp 140° C. (softens), 160°-170° C. (melts); Rf 0.65 (1:9 MeOH:CH2Cl2); 1H NMR (CDCl3) 7.62(d, 1H, J=6.87 Hz), 6.16(t, 1H, J=6.61), 5.73(d, 1H, J=5.70 Hz), 4.49(m, 1H), 3.93(m, 2H), 3.76(m, 1H), 2.30(m, 1H), 2.19(m, 1H), 0.89(s, 9H), 0.09(s, 6H)ppm.

1. customThe pyridine was removed under reduced pressure
2. dissolutionthe residue dissolved in DMF (30 ml)
3. stirringto stir overnight at room temperature
4. customThe DMF was removed under reduced pressure
5. dissolutionthe residue was dissolved in 80% aqueous acetic acid (20 ml)
6. temperatureto reflux for 30 min
7. temperaturecooled
8. customthe residue was purified by chromatography (1:1 EtOAc: hexanes)

ORD-Eintrag

ord-f0444523a49e4cf08888f5c50fd951e9

Quelldatensatz

uspto-grants-1993_08

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US05233031