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 275480Notes

Reaction equation

HRID 275480 reaction equation
[CH3:1][O:2][C:3](=[O:32])[C:4]([CH2:22][C:23]([C:25]1[CH:30]=[CH:29][C:28]([F:31])=[CH:27][CH:26]=1)=O)([CH2:9][C:10]([C:12]1[CH:17]=[CH:16][C:15]([S:18]([CH3:21])(=[O:20])=[O:19])=[CH:14][CH:13]=1)=O)[C:5]([O:7][CH3:8])=[O:6]>C1COCC1.[Zn].[Ti](Cl)(Cl)(Cl)Cl>[F:31][C:28]1[CH:29]=[CH:30][C:25]([C:23]2[CH2:22][C:4]([C:5]([O:7][CH3:8])=[O:6])([C:3]([O:2][CH3:1])=[O:32])[CH2:9][C:10]=2[C:12]2[CH:17]=[CH:16][C:15]([S:18]([CH3:21])(=[O:19])=[O:20])=[CH:14][CH:13]=2)=[CH:26][CH:27]=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 dimethyl2-[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
  9. dry with materialdried (MgSO4)
  10. concentrationconcentrated in vacuo
  11. customThe residue was chromatographed on silica gel

Sources & evidence

ORD record
ord-77ff17222346458d96e6c3708fe00523
Source dataset
uspto-grants-1995_02
Patent number
US05393790

Reaction notes

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