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

HRID 2244648Notes

Reaction equation

HRID 2244648 reaction equation
[F:1][C:2]([F:31])([F:30])[C:3]1[CH:4]=[C:5]([C:16]2[O:20][N:19]=[C:18]([C:21]3[CH:29]=[CH:28][CH:27]=[C:26]4[C:22]=3[CH:23]=[CH:24][NH:25]4)[N:17]=2)[CH:6]=[CH:7][C:8]=1[O:9][CH:10]([CH3:15])[C:11]([F:14])([F:13])[F:12].[H-].[Na+].[C:34](=[O:37])(O)[OH:35].[CH3:38]Cl.O>CN(C=O)C>[F:31][C:2]([F:1])([F:30])[C:3]1[CH:4]=[C:5]([C:16]2[O:20][N:19]=[C:18]([C:21]3[CH:29]=[CH:28][CH:27]=[C:26]4[C:22]=3[CH:23]=[CH:24][N:25]4[C:34]([O:35][CH3:38])=[O:37])[N:17]=2)[CH:6]=[CH:7][C:8]=1[O:9][CH:10]([CH3:15])[C:11]([F:12])([F:13])[F:14]

Participants

6

Reactant 4

HCID 962WaterHCID 24758Sodium hydrideHCID 592141764-{5-[3-(trifluoromethyl)-4-(2,2,2-trifluoro-1-methylethoxy)phenyl]-1,2,4-oxadiazol-3-yl}-1H-indoleHCID 86628811Methyl chloride carbonate

Product 1

HCID 59214238methyl 4-{5-[3-(trifluoromethyl)-4-(2,2,2-trifluoro-1-methylethoxy)phenyl]-1,2,4-oxadiazol-3-yl}-1H-indole-1-carboxylate

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

4-{5-[3-(Trifluoromethyl)-4-(2,2,2-trifluoro-1-methylethoxy)phenyl]-1,2,4-oxadiazol-3-yl}-1H-indole (100 mg) was dissolved in DMF (1.0 ml), followed by addition of 60% NaH (10.9 mg) at 0° C., and stirring at room temperature for 0.5 hour. Methyl chloride carbonate (26.3 μl) was added thereto at 0° C., followed by stirring at room temperature for 3 hours. 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, chloroform:CH3OH=100:0 to 98:2) to obtain methyl 4-{5-[3-(trifluoromethyl)-4-(2,2,2-trifluoro-1-methylethoxy)phenyl]-1,2,4-oxadiazol-3-yl}-1H-indole-1-carboxylate (98.6 mg) as a white solid.

Workup

  1. customat 0° C.
  2. stirringby stirring at room temperature for 3 hours
  3. extractionfollowed by extraction three times with EtOAc (20 ml)
  4. washwashed with saturated brine
  5. dry with materialdried over anhydrous MgSO4
  6. filtrationfiltered
  7. concentrationthe filtrate was concentrated
  8. customThe residue was purified by silica gel column chromatography (automatic purifier, chloroform:CH3OH=100:0 to 98:2)

Sources & evidence

ORD record
ord-2a8562f046064e7981d4986d0eb11ef9
Source dataset
uspto-grants-2010_03
Patent number
US07678820B2

Reaction notes

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