Dimethyl2-[2-(4-fluorophenyl)-2-oxoethyl]-2-[2-[4-(methylsulfonyl)phenyl]-2-oxoethyl]propanedioate → Dimethyl 3-(4-fluorophenyl)-4-(4-(methylsulfonyl)phenyl)cyclopent-3-ene-1,1-dicarboxylate

HRID 2292980Notes

Reaction equation

HRID 2292980 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8](=O)[CH2:9][C:10]([CH2:19][C:20]([C:22]2[CH:27]=[CH:26][C:25]([S:28]([CH3:31])(=[O:30])=[O:29])=[CH:24][CH:23]=2)=O)([C:15]([O:17][CH3:18])=[O:16])[C:11]([O:13][CH3:14])=[O:12])=[CH:4][CH:3]=1>C1COCC1.[Zn].[Ti](Cl)(Cl)(Cl)Cl>[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH2:9][C:10]([C:15]([O:17][CH3:18])=[O:16])([C:11]([O:13][CH3:14])=[O:12])[CH2:19][C:20]=2[C:22]2[CH:27]=[CH:26][C:25]([S:28]([CH3:31])(=[O:29])=[O:30])=[CH:24][CH:23]=2)=[CH:4][CH:3]=1

Participants

5

Reactant 1

HCID 10322194Dimethyl2-[2-(4-fluorophenyl)-2-oxoethyl]-2-[2-[4-(methylsulfonyl)phenyl]-2-oxoethyl]propanedioate

Product 1

HCID 10342760Dimethyl 3-(4-fluorophenyl)-4-(4-(methylsulfonyl)phenyl)cyclopent-3-ene-1,1-dicarboxylateYield 44.8%

Reagents, catalysts & solvents 3

HCID 23994ZincCatalystHCID 24193Titanium TetrachlorideCatalystHCID 8028TetrahydrofuranSolvent2×

Procedure

To a vigorously stirred mixture of 50.4 g (771 mmol) of zinc dust in 640 mL of THF at -78° C. under an atmosphere of nitrogen was added dropwise 60.4 mL (551 mmol) of titanium(IV) chloride. The reaction was warmed to ambient temperature with a water bath and then stirred at reflux for 1 hour. To the resulting dark mixture under reflux was added a solution of 15 g (32.3 mmol) of dimethyl 2-[2-(4-fluorophenyl)-2-oxoethyl]-2-[2-[4-(methylsulfonyl)phenyl]-2-oxoethyl]propanedioate (prepared above) in 20 mL of THF. The resulting mixture was stirred at ambient temperature for 16 hours, filtered through a pad of Celite, rinsed with ethyl acetate, and concentrated in vacuo. The residue was partitioned between water and ethyl acetate; the organic phase was washed with brine, dried MgSO4), and concentrated in vacuo. The residue was chromatographed on silica gel to give 6.26 g (44%) of 1-[2-(4-fluorophenyl)-4,4-dicarbomethoxycyclopenten-1-yl]-4-(methylsulfonyl)benzene which was identical to the material prepared in Step 8, Method A.

Workup

  1. temperatureat reflux for 1 hour
  2. temperatureTo the resulting dark mixture under reflux
  3. stirringThe resulting mixture was stirred at ambient temperature for 16 hours
  4. filtrationfiltered through a pad of Celite
  5. washrinsed with ethyl acetate
  6. concentrationconcentrated in vacuo
  7. customThe residue was partitioned between water and ethyl acetate
  8. washthe organic phase was washed with brine, dried MgSO4), and
  9. concentrationconcentrated in vacuo
  10. customThe residue was chromatographed on silica gel

Sources & evidence

ORD record
ord-aa920def76834ccf8521cb67f26851e2
Source dataset
uspto-grants-1997_11
Patent number
US05684195

Reaction notes

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