Reaktion #318812

Reaktionsgleichung

1,3-dimethyl-9-(4-fluorobenzyl)-6-hydroxy-pyrimido[2,1-f]purine-2,4,8(1H,3H,9H)-trione

ammonium sulfate

1,1,1,3,3,3-hexamethyldisilazane

lithium borohydride

hexamethyldisilazane

→

title compound

2,3-Dihydro-1,3-Dimethyl-9-(4-Fluorobenzyl)-6-Hydroxy-Pyrimido[2,1-f]Purine-4,8(1H,9H)-Dione

Lösungsmittel

chloroform

chloroform

1,4-dioxan

Reaktionsbedingungen

Aufarbeitung

1. 1
   TemperaturReflux
2. 2
   Sonstigeis obtained (18-24 hr.)
3. 3
   Sonstigeor until all starting material has been consumed (as determined by TLC on silica with chloroform(90)-methanol(10)-acetic acid(1))
4. 4
   SonstigeRemove a portion of the dioxane under reduced pressure
5. 5
   Sonstigepurge the system with nitrogen as the vacuum
6. 6
   Temperaturto cool
7. 7
   workup.ADDITIONadd 3 liters of chloroform
8. 8
   workup.ADDITIONAdd 1.3 liters of water cautiously (because of foaming)
9. 9
   workup.STIRRINGStir for one hour
10. 10
    Sonstigethen separate the layers
11. 11
    ExtraktionExtract the aqueous phase with two 1.3-liter volumes of chloroform
12. 12
    Trocknendry the combined extracts over anhydrous sodium sulfate
13. 13
    FiltrationFilter off the drying agent
14. 14
    Sonstigeremove solvent from the filtrate under reduced pressure
15. 15
    workup.DISSOLUTIONDissolve the residual tacky solid in 1.5 liters of boiling acetonitrile
16. 16
    workup.ADDITIONadd a small amount of decolorizing carbon
17. 17
    Temperaturreflux for 15 minutes
18. 18
    Filtrationfilter through a pad of Celite
19. 19
    TemperaturChill the filtrate
20. 20
    Sonstigecollect the resultant crystals
21. 21
    WaschenWash the crystals with cold acetonitrile
22. 22
    Sonstigedry them under vacuum at 50° C.

Vorschrift

Reflux a suspension of 395 g (1.06 moles) of 1,3-dimethyl-9-(4-fluorobenzyl)-6-hydroxy-pyrimido[2,1-f]purine-2,4,8(1H,3H,9H)-trione, 12.32 g of ammonium sulfate and 350 ml of 1,1,1,3,3,3-hexamethyldisilazane in 4 liters of chloroform until a clear solution is obtained (18-24 hr.). Remove chloroform and excess hexamethyldisilazane under reduced pressure, and treat the residual thick gum with 9.6 liters of dry 1,4-dioxan. While stirring the resultant mixture, cautiously add 70.4 g (3.24 moles) of lithium borohydride in portions under a stream of dry nitrogen. When foaming subsides, heat the mixture to 100° C. for 18 hr. or until all starting material has been consumed (as determined by TLC on silica with chloroform(90)-methanol(10)-acetic acid(1)). Remove a portion of the dioxane under reduced pressure, purge the system with nitrogen as the vacuum is released, allow the residue to cool, and add 3 liters of chloroform with stirring. Add 1.3 liters of water cautiously (because of foaming), followed by 2.3 liters of 3N hydrochloric acid. Stir for one hour; then separate the layers. Extract the aqueous phase with two 1.3-liter volumes of chloroform, and dry the combined extracts over anhydrous sodium sulfate. Filter off the drying agent, and remove solvent from the filtrate under reduced pressure. Dissolve the residual tacky solid in 1.5 liters of boiling acetonitrile, add a small amount of decolorizing carbon, reflux for 15 minutes, and filter through a pad of Celite. Chill the filtrate, and collect the resultant crystals. Wash the crystals with cold acetonitrile, and dry them under vacuum at 50° C. to obtain the title compound, mp 214°-232° C.

Quelle