Reaktion #80263

Reaktionsgleichung

Methyl 8-(N-Cbz-amino)-3-oxo-octanoate

methyl 8-(N-Cbz-amino)-3-oxo-octanoate

methanol

→

8-(N-Cbz-amino)-1,3-octanediol

Ausbeute 48.7%

Lösungsmittel

tetrahydrofuran

Reaktionsbedingungen

Aufarbeitung

1. 1
   Sonstigeequipped with a magnetic stirbar
2. 2
   Temperaturreflux condenser
3. 3
   workup.ADDITIONaddition funnel and nitrogen gas inlet
4. 4
   workup.ADDITIONwas cautiously added
5. 5
   TemperaturThe mixture was then heated
6. 6
   Temperaturto reflux
7. 7
   workup.STIRRINGStirring
8. 8
   Temperaturat reflux temperature for 60 minutes
9. 9
   workup.ADDITIONafter the addition
10. 10
    workup.DISTILLATIONdistilled water (78 mL)
11. 11
    workup.ADDITIONwas added
12. 12
    workup.ADDITION3N HCl was added to pH 3
13. 13
    SonstigeThe mixture was evaporated in vacuo
14. 14
    Sonstigeto remove the organic solvents, and solid potassium carbonate
15. 15
    workup.ADDITIONwas added
16. 16
    ExtraktionThe mixture was then extracted with ethyl acetate (5×100 mL)
17. 17
    WaschenThe extract was washed with saturated sodium chloride (2×50 mL)
18. 18
    Trocknendried over sodium sulfate
19. 19
    Filtrationfiltered
20. 20
    Sonstigeevaporated in vacuo
21. 21
    workup.DISSOLUTIONThe residue was dissolved in methanol (200 mL)
22. 22
    Sonstigeevaporated again
23. 23
    SonstigeThe residue was crystallized from ether (700 mL)

Vorschrift

Methyl 8-(N-Cbz-amino)-3-oxo-octanoate (3, 51.5 g, 0.16 moles) was dissolved in anhydrous tetrahydrofuran (350 mL) in a reaction flask equipped with a magnetic stirbar, reflux condenser, pressure equalizing addition funnel and nitrogen gas inlet. While stirring the mixture under nitrogen sodium borohydride (15.1 g, 0.4 moles) was cautiously added. The mixture was then heated to reflux and methanol was added dropwise over 90 minutes. Stirring was continued at reflux temperature for 60 minutes after the addition was complete. After allowing the solution to cool to ambient temperature, distilled water (78 mL) was added and 3N HCl was added to pH 3. The mixture was evaporated in vacuo to remove the organic solvents, and solid potassium carbonate was added to adjust the pH back to 12. The mixture was then extracted with ethyl acetate (5×100 mL). The extract was washed with saturated sodium chloride (2×50 mL), dried over sodium sulfate, filtered and evaporated in vacuo. The residue was dissolved in methanol (200 mL) and evaporated again. This was repeated a total of five times. The residue was crystallized from ether (700 mL) giving 8-(N-Cbz-amino)-1,3-octanediol (4, 23 g). A second crop was collected on addition of cyclohexane (300 mL) to the mother liquor (6.8 g). Mass Spectrum: (M+H)+ (M+H)+ @m/z 296, (M+NH4)+ @m/z 313.

Quelle