Acetic Acid → 1-(diphenylmethyl)-3-(4-fluoro-2-hydroxy-5-methoxyphenyl)-1,3-dihydro-2H-indol-2-one

HRID 1407477Notes

Reaction equation

HRID 1407477 reaction equation
[C:1]1([CH:7]([C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=2)[N:8]2[C:16]3[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=3)[C:10]([C:18]3[CH:23]=[C:22]([O:24][CH3:25])[C:21]([F:26])=[CH:20][C:19]=3[OH:27])(O)[C:9]2=[O:28])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C(N(CC)CC)C.S(Cl)(Cl)=O.C(O)(=O)C>ClC(Cl)C.[Zn]>[C:29]1([CH:7]([C:1]2[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=2)[N:8]2[C:16]3[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=3)[CH:10]([C:18]3[CH:23]=[C:22]([O:24][CH3:25])[C:21]([F:26])=[CH:20][C:19]=3[OH:27])[C:9]2=[O:28])[CH:30]=[CH:31][CH:32]=[CH:33][CH:34]=1

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 8471TriethylamineHCID 24386Thionyl ChlorideHCID 67357402HCID 67357402, compound

Product 1

HCID 673773961-(diphenylmethyl)-3-(4-fluoro-2-hydroxy-5-methoxyphenyl)-1,3-dihydro-2H-indol-2-oneYield 17.3%

Reagents, catalysts & solvents 2

HCID 23994ZincCatalystHCID 63651,1-DichloroethaneSolvent

Procedure

To a solution of 1-(diphenylmethyl)-3-(4-fluoro-2-hydroxy-5-methoxyphenyl)-3-hydroxy-1,3-dihydro-2H-indol-2-one (6.60 g, 14.5 mmol) in dichloroethane (100 mL) were added triethylamine (4.55 g, 45.0 mmol) and thionyl chloride (3.57 g, 30.0 mmol) at 0° C. The reaction mixture was heated at reflux for 1 h. The reaction mixture was cooled down to ambient temperature and concentrated under reduced pressure. The residue was dissolved in tetrahydrofuran (100 mL) and acetic acid (10 mL) and zinc dust (6.54 g, 100.0 mmol) were added in small portions at ambient temperature. The reaction mixture was stirred at ambient temperature for 16 h and filtered. The filtrate was concentrated in vacuo to dryness. The residue was purified by column chromatography with a 20% to 80% gradient of ethyl acetate in hexanes to afford 1-(diphenylmethyl)-3-(4-fluoro-2-hydroxy-5-methoxyphenyl)-1,3-dihydro-2H-indol-2-one (1.10 g, 17%) as a colorless solid: MS (ES+) m/z 440.2 (M+1).

Workup

  1. temperatureThe reaction mixture was heated
  2. temperatureat reflux for 1 h
  3. concentrationconcentrated under reduced pressure
  4. dissolutionThe residue was dissolved in tetrahydrofuran (100 mL)
  5. filtrationfiltered
  6. concentrationThe filtrate was concentrated in vacuo to dryness
  7. customThe residue was purified by column chromatography with a 20% to 80% gradient of ethyl acetate in hexanes

Sources & evidence

ORD record
ord-144b7631aaad4ac6aff3f24a6af976e9
Source dataset
uspto-grants-2014_12
Patent number
US08916580B2

Reaction notes

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