Triethylamine → 3,3-Bis-(4-hydroxy-3,5-dimethyl-phenyl)-1-[3-(4-methoxy-phenyl)-[1,2,4]oxadiazol-5-ylmethyl]-1,3-dihydro-indol-2-one

HRID 1297800Notes

Reaction equation

HRID 1297800 reaction equation
[OH:1][C:2]1[C:7]([CH3:8])=[CH:6][C:5]([C:9]2([C:22]3[CH:27]=[C:26]([CH3:28])[C:25]([OH:29])=[C:24]([CH3:30])[CH:23]=3)[C:17]3[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=3)[N:11]([CH2:18][C:19]#[N:20])[C:10]2=[O:21])=[CH:4][C:3]=1[CH3:31].[OH:32][N:33]=[C:34](Cl)[C:35]1[CH:40]=[CH:39][C:38]([O:41][CH3:42])=[CH:37][CH:36]=1.C(N(CC)CC)C.[F-].C([N+](CCCC)(CCCC)CCCC)CCC>C(OCC)C.C1COCC1.O.C(OCC)(=O)C>[OH:29][C:25]1[C:26]([CH3:28])=[CH:27][C:22]([C:9]2([C:5]3[CH:4]=[C:3]([CH3:31])[C:2]([OH:1])=[C:7]([CH3:8])[CH:6]=3)[C:17]3[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=3)[N:11]([CH2:18][C:19]3[O:32][N:33]=[C:34]([C:35]4[CH:40]=[CH:39][C:38]([O:41][CH3:42])=[CH:37][CH:36]=4)[N:20]=3)[C:10]2=[O:21])=[CH:23][C:24]=1[CH3:30]

Participants

9

Reactant 4

HCID 8471TriethylamineHCID 2724141Tetrabutylammonium FluorideHCID 27633714-Methoxy-N-hydroxybenzenecarboximidoyl chlorideHCID 86597007[3,3-Bis-(4-hydroxy-3,5-dimethyl-phenyl)-2-oxo-2,3-dihydro-indol-1-yl]-acetonitrile

Product 1

HCID 589147213,3-Bis-(4-hydroxy-3,5-dimethyl-phenyl)-1-[3-(4-methoxy-phenyl)-[1,2,4]oxadiazol-5-ylmethyl]-1,3-dihydro-indol-2-oneYield 27.8%

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 3283Diethyl EtherSolvent2×HCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

Combine [3,3-Bis-(4-hydroxy-3,5-dimethyl-phenyl)-2-oxo-2,3-dihydro-indol-1-yl]-acetonitrile (0.563 g, 0.878 mmol), N-hydroxy-4-methoxy-benzenecarboximidoyl chloride (1.63 g, 8.78 mmol), and diethyl ether (20 mL). Add a solution of triethylamine (1.35 mL, 9.66 mmol) in diethyl ether (10 mL) over 30 minutes. Stir the reaction at room temperature overnight. Dilute the reaction with ethyl acetate (200 mL) and water (200 mL). Separate the layers, and dry the organic layer with sodium sulfate. Concentrate in vacuo. Chromatograph on silica gel eluting with 20% ethyl acetate in hexanes and concentrate. Dissolve the resulting compound (0.217 g, 0.275 mmol) in THF (2 mL). Add a solution of tetrabutylammonium fluoride (1.0 M) in THF (0.69 mL) and stir the reaction at room temperature for 30 minutes. Quench with 1N aqueous HCl (10 mL), ethyl acetate (50 mL), and water (40 mL). Separate the layers and wash the organic layer with brine (50 mL). Dry the ethyl acetate with sodium sulfate, and concentrate in vacuo. Chromatograph on silica gel eluting with a gradient from 25% to 50% ethyl acetate in hexanes to give 0.137 g of the title compound: mass spectrum (ion spray): m/z=562(M+1); 1H NMR(DMSO-d6): δ8.23 (s, 2H), 7.84-7.82 (m, 2H), 7.28-7.25 (m, 2H), 7.16-7.04 (m, 6H), 6.71 (s, 4H), 5.42 (s, 2H), 3.81 (s, 3H), 2.04 (s, 12H).

Workup

  1. customthe reaction at room temperature overnight
  2. additionDilute
  3. customSeparate the layers
  4. dry with materialdry the organic layer with sodium sulfate
  5. concentrationConcentrate in vacuo
  6. concentrationChromatograph on silica gel eluting with 20% ethyl acetate in hexanes and concentrate
  7. stirringstir
  8. customthe reaction at room temperature for 30 minutes
  9. customQuench with 1N aqueous HCl (10 mL), ethyl acetate (50 mL), and water (40 mL)
  10. customSeparate the layers
  11. washwash the organic layer with brine (50 mL)
  12. dry with materialDry the ethyl acetate with sodium sulfate
  13. concentrationconcentrate in vacuo

Sources & evidence

ORD record
ord-b06b1398f7e6431da16e216057445028
Source dataset
uspto-grants-2007_07
Patent number
US07250442B2

Reaction notes

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