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

HRID 552856Notes

Reaction equation

HRID 552856 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[CH2:23][CH2:24][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](Cl)(=[O:36])[CH3:35].O>CN(C=O)C>[C:34]([N:25]1[C:26]2[C:22](=[C:21]([C:18]3[N:17]=[C:16]([C:5]4[CH:6]=[CH:7][C:8]([O:9][CH:10]([CH3:15])[C:11]([F:12])([F:13])[F:14])=[C:3]([C:2]([F:1])([F:30])[F:31])[CH:4]=4)[O:20][N:19]=3)[CH:29]=[CH:28][CH:27]=2)[CH2:23][CH2:24]1)(=[O:36])[CH3:35]

Participants

6

Reactant 4

HCID 962WaterHCID 6367Acetyl chlorideHCID 24758Sodium hydrideHCID 592143624-{5-[3-(Trifluoromethyl)-4-(2,2,2-trifluoro-1-methylethoxy)phenyl]-1,2,4-oxadiazol-3-yl}indoline

Product 1

HCID 592141661-Acetyl-4-{5-[3-(trifluoromethyl)-4-(2,2,2-trifluoro-1-methylethoxy)phenyl]-1,2,4-oxadiazol-3-yl}indoline

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 4-{5-[3-(trifluoromethyl)-4-(2,2,2-trifluoro-1-methylethoxy)phenyl]-1,2,4-oxadiazol-3-yl}indoline (100 mg) in DMF (1.0 ml) was added 60% NaH (10.9 mg) at 0° C., followed by stirring at room temperature for 0.5 hour. Acetyl chloride (24.1 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 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 60:40) to obtain 1-acetyl-4-{5-[3-(trifluoromethyl)-4-(2,2,2-trifluoro-1-methylethoxy)phenyl]-1,2,4-oxadiazol-3-yl}indoline (56.8 mg) as a white crystal.

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. washThe organic layer was washed 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, n-hexane:EtOAc=90:10 to 60:40)

Sources & evidence

ORD record
ord-96cb428cda31484b81c950a314840046
Source dataset
uspto-grants-2011_05
Patent number
US07951825B2

Reaction notes

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