1,3-Dioxolane → Acyclovir

Temperature

70 °C

A mixture of guanine (25 g) , hexamethyldisilazane (HMDS, 125 ml), and trimethylsilyl trifluoromethanesulfonate (1 ml) was heated to reflux (130°-135° C.) for 24 hours. The resulting mixture was cooled to 70° C., 1,3-dioxolane (25 ml) added, and the resulting mixture refluxed for 16 hours. Excess HMDS and 1,3-dioxolane were removed by distillation under reduced pressure. The reaction mixture was cooled to 70° C., and poured into a mixture of 600 ml of 10% aqueous acetic acid. The mixture was heated to give a solution. The hot solution was treated with a small amount of activated carbon (1.25 g) to remove any color, filtered, and the filtrate slowly cooled to 5° C. The white crystalline solid thus produced was filtered off, to yield pure 9-(2-hydroxyethoxymethyl)guanine (29 g, 78%). 1H NMR: 3.38 (4H, singlet); 4.64 (1H, broad singlet); 5.26 (2H, singlet); 6.54 (2H, broad singlet); 7.68 (1H, singlet).

1. temperaturewas heated
2. temperatureto reflux (130°-135° C.) for 24 hours
3. temperaturethe resulting mixture refluxed for 16 hours
4. customExcess HMDS and 1,3-dioxolane were removed by distillation under reduced pressure
5. temperatureThe reaction mixture was cooled to 70° C.
6. additionpoured into a mixture of 600 ml of 10% aqueous acetic acid
7. temperatureThe mixture was heated
8. customto give a solution
9. additionThe hot solution was treated with a small amount of activated carbon (1.25 g)
10. customto remove any color
11. filtrationfiltered
12. temperaturethe filtrate slowly cooled to 5° C
13. customThe white crystalline solid thus produced
14. filtrationwas filtered off

ORD record

ord-0c31d9515dc24f5cab882602553be449

Source dataset

uspto-grants-1996_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05567816