Ammonium Chloride → 1-(diphenylmethyl)-3-(5-fluoro-7-hydroxy-2,3-dihydro-1,4-benzodioxin-6-yl)-3-hydroxy-1,3-dihydro-2H-indol-2-one

HRID 1965373Notes

Reaction equation

HRID 1965373 reaction equation
[F:1][C:2]1[C:7]2[O:8][CH2:9][CH2:10][O:11][C:6]=2[CH:5]=[C:4]([OH:12])[CH:3]=1.C([Mg]Cl)(C)C.[C:18]1([CH:24]([C:36]2[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=2)[N:25]2[C:33]3[C:28](=[CH:29][CH:30]=[CH:31][CH:32]=3)[C:27](=[O:34])[C:26]2=[O:35])[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1.[Cl-].[NH4+]>ClCCl.O1CCCC1>[C:36]1([CH:24]([C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)[N:25]2[C:33]3[C:28](=[CH:29][CH:30]=[CH:31][CH:32]=3)[C:27]([C:3]3[C:4]([OH:12])=[CH:5][C:6]4[O:11][CH2:10][CH2:9][O:8][C:7]=4[C:2]=3[F:1])([OH:34])[C:26]2=[O:35])[CH:37]=[CH:38][CH:39]=[CH:40][CH:41]=1

Participants

7

Reactant 4

HCID 25517Ammonium ChlorideHCID 19692771-(diphenylmethyl)-1H-indole-2,3-dioneHCID 673575678-Fluoro-2,3-dihydro-1,4-benzodioxin-6-olHCID 178418918HCID 178418918, compound

Product 1

HCID 673575191-(diphenylmethyl)-3-(5-fluoro-7-hydroxy-2,3-dihydro-1,4-benzodioxin-6-yl)-3-hydroxy-1,3-dihydro-2H-indol-2-oneYield 64%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

A 100 mL round-bottom flask was charged with 8-fluoro-2,3-dihydrobenzo[b][1,4]dioxin-6-ol (6.4 g, 37 mmol) and tetrahydrofuran (60 mL). A 2 M solution of isopropylmagnesium chloride in tetrahydrofuran (20.0 mL, 40.0 mmol) was added at 5° C. and the reaction mixture was stirred for 15 min. The reaction mixture was concentrated in vacuo and dichloromethane (60 mL) was added, followed by a solution of 1-(diphenylmethyl)-1H-indole-2,3-dione (10.9 g, 35.0 mmol) in dichloromethane (60 mL). The reaction mixture was heated at reflux for 5 h, allowed to cool to ambient temperature and stirred for a further 16 h. Saturated aqueous ammonium chloride (30 mL) was added and the phases were separated. The organic phase was dried over magnesium sulfate, filtered and concentrated in vacuo. Trituration of the residue in methanol (30 mL) afforded 1-(diphenylmethyl)-3-(5-fluoro-7-hydroxy-2,3-dihydro-1,4-benzodioxin-6-yl)-3-hydroxy-1,3-dihydro-2H-indol-2-one (10.8 g, 64%) as an off-white solid: MS (ES+) m/z 506.0 (M+23).

Workup

  1. concentrationThe reaction mixture was concentrated in vacuo and dichloromethane (60 mL)
  2. additionwas added
  3. temperatureThe reaction mixture was heated
  4. temperatureat reflux for 5 h
  5. stirringstirred for a further 16 h
  6. customthe phases were separated
  7. dry with materialThe organic phase was dried over magnesium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-56de97b0ee4b4da694f66ff19f577cb9
Source dataset
uspto-grants-2013_04
Patent number
US08415370B2

Reaction notes

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