Ammonium Chloride → 1-(diphenylmethyl)-3-hydroxy-3-(5-hydroxy-1-benzothiophen-6-yl)-1,3-dihydro-2H-indol-2-one

HRID 1965377Notes

Reaction equation

HRID 1965377 reaction equation
[S:1]1[CH:5]=[CH:4][C:3]2[CH:6]=[C:7]([OH:10])[CH:8]=[CH:9][C:2]1=2.C([Mg]Cl)(C)C.[C:16]1([CH:22]([C:34]2[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=2)[N:23]2[C:31]3[C:26](=[CH:27][CH:28]=[CH:29][CH:30]=3)[C:25](=[O:32])[C:24]2=[O:33])[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1.[Cl-].[NH4+]>O1CCCC1.ClCCCl>[C:34]1([CH:22]([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)[N:23]2[C:31]3[C:26](=[CH:27][CH:28]=[CH:29][CH:30]=3)[C:25]([OH:32])([C:8]3[C:7]([OH:10])=[CH:6][C:3]4[CH:4]=[CH:5][S:1][C:2]=4[CH:9]=3)[C:24]2=[O:33])[CH:35]=[CH:36][CH:37]=[CH:38][CH:39]=1

Participants

7

Reactant 4

HCID 25517Ammonium ChlorideHCID 19692771-(diphenylmethyl)-1H-indole-2,3-dioneHCID 12203499Benzo[b]thiophen-5-olHCID 178418918HCID 178418918, compound

Product 1

HCID 685980971-(diphenylmethyl)-3-hydroxy-3-(5-hydroxy-1-benzothiophen-6-yl)-1,3-dihydro-2H-indol-2-oneYield 59.3%

Reagents, catalysts & solvents 2

HCID 111,2-DichloroethaneSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
5 °C

Procedure

To a solution of benzo[b]thiophen-5-ol (1.39 g, 9.25 mmol) in tetrahydrofuran (50 mL) at 5° C. was added a 2 M solution of isopropylmagnesium chloride in tetrahydrofuran (5.0 mL, 10 mmol). The reaction mixture was stirred at 5° C. for 15 min and concentrated in vacuo. To the residue were added 1,2-dichloroethane (100 mL) and 1-(diphenylmethyl)-1H-indole-2,3-dione (2.5 g, 8.0 mmol). The reaction mixture was heated at reflux for 3 h, allowed to cool to ambient temperature and stirred for 48 h. Saturated aqueous ammonium chloride (10 mL) was added and the phases were separated. The organic phase was dried over magnesium sulfate, filtered and concentrated in vacuo. The residue was purified by column chromatography and eluted with a 0% to 20% gradient of ethyl acetate in dichloromethane to afford 1-(diphenylmethyl)-3-hydroxy-3-(5-hydroxy-1-benzothiophen-6-yl)-1,3-dihydro-2H-indol-2-one (2.2 g, 59%) as an off-white solid: MS (ES+) m/z 486.0 (M+23).

Workup

  1. concentrationconcentrated in vacuo
  2. temperatureThe reaction mixture was heated
  3. temperatureat reflux for 3 h
  4. temperatureto cool to ambient temperature
  5. stirringstirred for 48 h
  6. customthe phases were separated
  7. dry with materialThe organic phase was dried over magnesium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customThe residue was purified by column chromatography
  11. washeluted with a 0% to 20% gradient of ethyl acetate in dichloromethane

Sources & evidence

ORD record
ord-0a109c1c7d044820ba6ef490c0859cf3
Source dataset
uspto-grants-2013_04
Patent number
US08415370B2

Reaction notes

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