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Water → 4-{5-[3-(trifluoromethyl)-4-(2,2,2-trifluoro-1-methylethoxy)phenyl]-1,2,4-oxadiazol-3-yl}-1H-indole-3-carboaldehyde

HRID 552862
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HRID 552862 반응식
O=P(Cl)(Cl)Cl.[F:6][C:7]([F:36])([F:35])[C:8]1[CH:9]=[C:10]([C:21]2[O:25][N:24]=[C:23]([C:26]3[CH:34]=[CH:33][CH:32]=[C:31]4[C:27]=3[CH:28]=[CH:29][NH:30]4)[N:22]=2)[CH:11]=[CH:12][C:13]=1[O:14][CH:15]([CH3:20])[C:16]([F:19])([F:18])[F:17].[OH-].[Na+].O.CN([CH:43]=[O:44])C>>[F:36][C:7]([F:6])([F:35])[C:8]1[CH:9]=[C:10]([C:21]2[O:25][N:24]=[C:23]([C:26]3[CH:34]=[CH:33][CH:32]=[C:31]4[C:27]=3[C:28]([CH:43]=[O:44])=[CH:29][NH:30]4)[N:22]=2)[CH:11]=[CH:12][C:13]=1[O:14][CH:15]([CH3:20])[C:16]([F:17])([F:18])[F:19]
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6

반응물 5

HCID 962WaterHCID 6228Dimethylformamide2회HCID 14798Sodium HydroxideHCID 24813Phosphorus oxychlorideHCID 592141764-{5-[3-(trifluoromethyl)-4-(2,2,2-trifluoro-1-methylethoxy)phenyl]-1,2,4-oxadiazol-3-yl}-1H-indole

생성물 1

HCID 59214403
4-{5-[3-(trifluoromethyl)-4-(2,2,2-trifluoro-1-methylethoxy)phenyl]-1,2,4-oxadiazol-3-yl}-1H-indole-3-carboaldehyde

실험 절차

POCl3 (158.4 μl) was added dropwise to a DMF solution (4 ml) at 0° C. After warming to room temperature, it was stirred for 0.5 hour. Then, a solution of 4-{5-[3-(trifluoromethyl)-4-(2,2,2-trifluoro-1-methylethoxy)phenyl]-1,2,4-oxadiazol-3-yl}-1H-indole (500.0 mg) in DMF (1 ml) was added thereto at 0° C., followed by stirring at room temperature for 15 hours. After cooling to 0° C., to the reaction solution was added a 1M aqueous NaOH solution for adjustment of its pH to 9 to 10. This solution was stirred at 100° C. for 1 hour. After being left to be cooled, to the reaction solution was added water (30 ml), followed by extraction three times with EtOAc (20 ml). The organic layer was combined, washed with saturated brine, dried over anhydrous MgSO4, and then filtered, and the filtrate was concentrated. The residue was purified by silica gel column chromatography (automatic purifier, n-hexane, EtOAc=90:10 to 70:30) to obtain 4-{5-[3-(trifluoromethyl)-4-(2,2,2-trifluoro-1-methylethoxy)phenyl]-1,2,4-oxadiazol-3-yl}-1H-indole-3-carboaldehyde (456.7 mg) as a white solid.

후처리

  1. customat 0° C.
  2. stirringby stirring at room temperature for 15 hours
  3. temperatureAfter cooling to 0° C., to the reaction solution
  4. stirringThis solution was stirred at 100° C. for 1 hour
  5. waitAfter being left
  6. temperatureto be cooled, to the reaction solution
  7. extractionfollowed by extraction three times with EtOAc (20 ml)
  8. washwashed with saturated brine
  9. dry with materialdried over anhydrous MgSO4
  10. filtrationfiltered
  11. concentrationthe filtrate was concentrated
  12. customThe residue was purified by silica gel column chromatography (automatic purifier, n-hexane, EtOAc=90:10 to 70:30)

출처 및 근거

ORD 기록
ord-fbf3a5d5b1624876a07428c7fbd5e0ba
출처 데이터셋
uspto-grants-2011_05
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US07951825B2

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