反応 #158288

反応方程式

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

溶媒

DMF

反応条件

後処理

1. 1
   workup.ADDITIONwas added to the reaction mixture
2. 2
   抽出the mixture was extracted with ethyl acetate
3. 3
   乾燥The extract was dried over anhydrous magnesium sulfate
4. 4
   その他the solvent was evaporated under reduced pressure
5. 5
   その他The 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
    抽出the mixture was extracted with ethyl acetate
11. 11
    乾燥The extract was dried over anhydrous magnesium sulfate
12. 12
    その他the solvent was evaporated under reduced pressure
13. 13
    その他The 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
    温度to cool to room temperature
18. 18
    ろ過the precipitate was filtered off
19. 19
    その他the 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
    温度under heating
23. 23
    温度with reflux for 1 hr
24. 24
    濃縮The reaction mixture was concentrated
25. 25
    その他the residue was purified by silica gel column chromatography (ethyl acetate/hexane)

実験手順

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).

出典