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

HRID 2244652Notes

Reaction equation

HRID 2244652 reaction equation
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]

Participants

6

Reactant 5

HCID 962WaterHCID 6228Dimethylformamide2×HCID 14798Sodium HydroxideHCID 24813Phosphorus oxychlorideHCID 592141764-{5-[3-(trifluoromethyl)-4-(2,2,2-trifluoro-1-methylethoxy)phenyl]-1,2,4-oxadiazol-3-yl}-1H-indole

Product 1

HCID 592144034-{5-[3-(trifluoromethyl)-4-(2,2,2-trifluoro-1-methylethoxy)phenyl]-1,2,4-oxadiazol-3-yl}-1H-indole-3-carboaldehyde

Procedure

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.

Workup

  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)

Sources & evidence

ORD record
ord-e704fe6ff0834b659cb7c6762c9f2676
Source dataset
uspto-grants-2010_03
Patent number
US07678820B2

Reaction notes

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