Reaktion #158288

Reaktionsgleichung

ammonium chloride

sodium hydride

2-(3,4-difluorobenzyl)-5-[3-methoxy-4-(2-methyl-1,3-oxazol-5-yl)phenyl]-1,3,4-oxadiazole

tert-Butyl [2-chloro-1-(iodomethyl)ethoxy]dimethylsilane

→

title compound

(6RS,8SR)-6-{[tert-butyl(dimethyl)silyl]oxy}-8-(3,4-difluorophenyl)-3-[3-methoxy-4-(2-methyl-1,3-oxazol-5-yl)phenyl]-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridine

Lösungsmittel

DMF

Reaktionsbedingungen

Aufarbeitung

1. 1
   workup.ADDITIONwas added to the reaction mixture
2. 2
   Extraktionthe mixture was extracted with ethyl acetate
3. 3
   TrocknenThe extract was dried over anhydrous magnesium sulfate
4. 4
   Sonstigethe solvent was evaporated under reduced pressure
5. 5
   SonstigeThe residue was purified by silica gel column chromatography (ethyl acetate/hexane)
6. 6
   workup.ADDITIONTo a mixture of the purified product in DMSO (7.6 mL)
7. 7
   workup.ADDITIONwas added sodium azide (199 mg)
8. 8
   workup.STIRRINGthe mixture was stirred at 100° C. for 10 hr
9. 9
   workup.ADDITIONThe reaction mixture was diluted with ethyl acetate/brine
10. 10
    Extraktionthe mixture was extracted with ethyl acetate
11. 11
    TrocknenThe extract was dried over anhydrous magnesium sulfate
12. 12
    Sonstigethe solvent was evaporated under reduced pressure
13. 13
    SonstigeThe residue was purified by silica gel column chromatography (ethyl acetate)
14. 14
    workup.ADDITIONTo a mixture of the purified product in THF (46 mL)
15. 15
    workup.ADDITIONwere added diphenylphosphino-polystyrene (1.99 mmol/g, 4.58 g) and water (4.6 mL)
16. 16
    workup.STIRRINGthe mixture was stirred at 80° C. for 2 hr
17. 17
    Temperaturto cool to room temperature
18. 18
    Filtrationthe precipitate was filtered off
19. 19
    Sonstigethe filtrate was evaporated under reduced pressure
20. 20
    workup.ADDITIONToluene (46 mL) was added to the residue
21. 21
    workup.STIRRINGthe mixture was stirred
22. 22
    Temperaturunder heating
23. 23
    Temperaturwith reflux for 1 hr
24. 24
    EinengenThe reaction mixture was concentrated
25. 25
    Sonstigethe residue was purified by silica gel column chromatography (ethyl acetate/hexane)

Vorschrift

To a mixture of 2-(3,4-difluorobenzyl)-5-[3-methoxy-4-(2-methyl-1,3-oxazol-5-yl)phenyl]-1,3,4-oxadiazole (2.41 g) in DMF (45 mL) was added sodium hydride (60%, 264 mg) at 0° C., and the mixture was stirred for 10 min. tert-Butyl [2-chloro-1-(iodomethyl)ethoxy]dimethylsilane (2.52 g) was added to the reaction mixture, and the mixture was stirred at room temperature for 30 min. Saturated aqueous ammonium chloride solution was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The extract was dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate/hexane). To a mixture of the purified product in DMSO (7.6 mL) was added sodium azide (199 mg), and the mixture was stirred at 100° C. for 10 hr. The reaction mixture was diluted with ethyl acetate/brine, and the mixture was extracted with ethyl acetate. The extract was dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate). To a mixture of the purified product in THF (46 mL) were added diphenylphosphino-polystyrene (1.99 mmol/g, 4.58 g) and water (4.6 mL), and the mixture was stirred at 80° C. for 2 hr. The reaction mixture was allowed to cool to room temperature, the precipitate was filtered off, and the filtrate was evaporated under reduced pressure. Toluene (46 mL) was added to the residue, and the mixture was stirred under heating with reflux for 1 hr. The reaction mixture was concentrated, and the residue was purified by silica gel column chromatography (ethyl acetate/hexane) to give the title compound (415 mg).

Quelle