반응 #1011391

반응 방정식

4-(1-(4-(Trifluoromethoxy)phenyl)-1H-1,2,4-triazol-3-yl)benzaldehyde

Sodium hydride

Ethyl 2-fluoroacetate

→

ethyl 2-fluoro-3-hydroxy-3-(4-(1-(4-(trifluoromethoxy)phenyl)-1H-1,2,4-triazol-3-yl)phenyl)propanoate

반응 조건

후처리

1. 1
   기타oven-dried round bottomed flask
2. 2
   workup.ADDITIONDiethyl ether (9 mL) was added
3. 3
   온도the reaction was cooled in an ice bath
4. 4
   기타The ice bath was removed after 1 hour
5. 5
   workup.STIRRINGstirring for an additional 2 hours until the reaction
6. 6
   기타was quenched with saturated aqueous ammonium chloride
7. 7
   workup.ADDITIONdiluted with diethyl ether
8. 8
   workup.STIRRINGstirred at room temperature for 3 days
9. 9
   workup.ADDITIONThe biphasic solution was diluted with brine
10. 10
    추출extracted with ethyl acetate (2×)
11. 11
    여과filtered
12. 12
    농축concentrated
13. 13
    기타to give an orange liquid
14. 14
    기타The crude material was purified by reverse-phase flash column chromatography

실험 절차

Sodium hydride (60% oil immersion, 0.48 g, 12 mmol) was added to a dry, oven-dried round bottomed flask and placed under nitrogen. Diethyl ether (9 mL) was added, followed by absolute ethanol (0.05 mL), and the reaction was cooled in an ice bath. Ethyl 2-fluoroacetate (0.87 mL, 9.0 mmol) was added dropwise. The reaction was stirred for 15 minutes in ice bath (gas evolution ceased). 4-(1-(4-(Trifluoromethoxy)phenyl)-1H-1,2,4-triazol-3-yl)benzaldehyde (2.2 g, 6.5 mmol) was added in solid portions. The solution slowly turned color to a golden yellow. The ice bath was removed after 1 hour and warmed to room temperature, stirring for an additional 2 hours until the reaction was quenched with saturated aqueous ammonium chloride, diluted with diethyl ether, and stirred at room temperature for 3 days. The biphasic solution was diluted with brine and extracted with ethyl acetate (2×). The organic layers were dried organic over anhydrous sodium sulfate, filtered, and concentrated to give an orange liquid. The crude material was purified by reverse-phase flash column chromatography using 0-100% acetonitrile/water as eluent to afford the intermediate ethyl 2-fluoro-3-hydroxy-3-(4-(1-(4-(trifluoromethoxy)phenyl)-1H-1,2,4-triazol-3-yl)phenyl)propanoate as a crude compound (0.11 g).

출처