Reaktion #1884597

Reaktionsgleichung

compound 71

2-Amino-9-[4-(dimethylphenylsilyl)-3-(hydroxymethyl)-2-methylenecyclopentyl]-1,9-dihydro-6H-purin-6-one

acetic acid

→

title compound

2-Amino-1,9-dihydro-9-[4-hydroxy-3-(hydroxymethyl)-2-methylenecyclopentyl]-6H-purin-6-one

Lösungsmittel

MeOH

Reaktionsbedingungen

Aufarbeitung

1. 1
   SonstigeA 2-L 3-necked round bottomed flask, oven dried
2. 2
   Sonstigeequipped with a mechanical stirrer, an addition funnel
3. 3
   Temperaturcooled to room temperature
4. 4
   Sonstigequenched with aqueous KOH (10 N, ˜220 mL)
5. 5
   workup.ADDITIONwas added to the solution
6. 6
   TemperaturThe resulting solution was warmed to 70° C.
7. 7
   workup.STIRRINGstirred for 10 hours
8. 8
   TemperaturThe reaction was cooled to 5–10° C
9. 9
   workup.ADDITIONSodium bisulfite (16.2 g) was added portion-wise over 30 minutes
10. 10
    EinengenThe reaction mixture was concentrated in vacuo
11. 11
    Sonstigeto remove most of the MeOH
12. 12
    TemperaturThe resulting yellow semi-solid was cooled to −5° C.
13. 13
    workup.ADDITIONconcentrated HCl (˜55 mL) added
14. 14
    ExtraktionThe resulting solution was extracted with EtOAc (500 mL) and aqueous KOH (10 N, ˜48 mL)
15. 15
    workup.ADDITIONadded
16. 16
    workup.STIRRINGThe solution was stirred for 1 hour
17. 17
    workup.STIRRINGThe reaction mixture was stirred at room temperature for 1 hour and at ˜5° C. for 3 hours
18. 18
    FiltrationThe solid was collected by filtration
19. 19
    Sonstigedried under high vacuum for 16 hours
20. 20
    workup.DISSOLUTIONThe solid was redissolved in water (600 mL) at 90° C
21. 21
    TemperaturThe clear solution was cooled to ˜60–55° C.
22. 22
    Temperaturto cool to room temperature for 5 hours
23. 23
    FiltrationThe resulting white crystalline solid was collected by filtration
24. 24
    Sonstigedried under vacuum at 50° C. for 16 hours

Vorschrift

A 2-L 3-necked round bottomed flask, oven dried and equipped with a mechanical stirrer, an addition funnel, temperature probe, and argon inlet, was charged with compound 71 (34.1 g, 86.2 moles), acetic acid (40.4 mL, 8 eq) and acetic acid-boron trifluoride complex (38 mL). The reaction mixture was heated to 95° C., stirred for 4 hours and then cooled to room temperature. The reaction mixture was diluted with MeOH (200 mL) and quenched with aqueous KOH (10 N, ˜220 mL) to adjust the pH to about 9.5. Potassium bicarbonate (17.9 g) followed by aqueous hydrogen peroxide (30 wt. %, 39 g) was added to the solution. The resulting solution was warmed to 70° C. and stirred for 10 hours. The reaction was cooled to 5–10° C. Sodium bisulfite (16.2 g) was added portion-wise over 30 minutes. The reaction mixture was concentrated in vacuo to remove most of the MeOH. The resulting yellow semi-solid was cooled to −5° C. and concentrated HCl (˜55 mL) added to adjust the pH to 0.15. The resulting solution was extracted with EtOAc (500 mL) and aqueous KOH (10 N, ˜48 mL) added to adjust the pH to ˜11. The solution was stirred for 1 hour and then the pH was adjusted to ˜7 with HCl (4 mL). The reaction mixture was stirred at room temperature for 1 hour and at ˜5° C. for 3 hours. The solid was collected by filtration and dried under high vacuum for 16 hours. The solid was redissolved in water (600 mL) at 90° C. The clear solution was cooled to ˜60–55° C. and seeded with 21. The solution was allowed to cool to room temperature for 5 hours. The resulting white crystalline solid was collected by filtration and dried under vacuum at 50° C. for 16 hours to afford the title compound (12.9 g).

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