Hydrochloric Acid → 6-Deoxypenciclovir

Temperatur

45 °C

24.21 g (0.1 mole) of 2-amino-9-(2-bromoethyl)purine was completely dissolved in 120 ml of dimethylsulfoxide, to which 48.05 g (0.3 mole) of diethylmalonate and 41.46 g (03 mole) of potassium carbonate were then added. The mixture was stirred at a temperature of 40-50° C. for 4 hours. After completion of the reaction, the reaction product was cooled to room temperature, to which 300 ml of water was then added. The solution was then extracted three times with 400 ml portions of dichloromethane. The organic layer was collected, and dried with anhydrous magnesium sulfate, followed by filtration and washing. The filtrate was concentrated under reduced pressure. The remaining concentrate was added to 300 ml of t-butanol and then warmed to 60° C., followed by the addition of 21.06 g (0.61 mole) of sodium borohydride. To the resulting mixture, 30 ml of methanol was added slowly, followed by stirring for five hours. After completion of the reaction, the reaction product was cooled to room temperature, neutralized with diluted hydrochloric acid, and then concentrated. The remaining concentrate was added to 100 ml of methanol and then stirred for two hours at room temperature, followed by filtration. The filtrate was concentrated under reduced pressure and crystallized from butanol, thereby giving 13.05 g (55% yield) of light yellow-colored 2-amino-9-[4-hydroxy-3-(hydroxymethyl)but-1-yl]purine.

1. additionwere then added
2. customAfter completion of the reaction
3. additionwas then added
4. extractionThe solution was then extracted three times with 400 ml portions of dichloromethane
5. customThe organic layer was collected
6. dry with materialdried with anhydrous magnesium sulfate
7. filtrationfollowed by filtration
8. washwashing
9. concentrationThe filtrate was concentrated under reduced pressure
10. concentrationThe remaining concentrate
11. additionwas added to 300 ml of t-butanol
12. temperaturewarmed to 60° C.
13. stirringby stirring for five hours
14. customAfter completion of the reaction
15. temperaturethe reaction product was cooled to room temperature
16. concentrationconcentrated
17. concentrationThe remaining concentrate
18. additionwas added to 100 ml of methanol
19. stirringstirred for two hours at room temperature
20. filtrationfollowed by filtration
21. concentrationThe filtrate was concentrated under reduced pressure
22. customcrystallized from butanol

ORD-Eintrag

ord-01346a2ab20747b7802f6060f4733106

Quelldatensatz

uspto-grants-2008_11

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US07456282B2