Hydrochloric Acid → 2-(4-Fluorophenyl)-3-[4-(methylsulfonyl)phenyl]-5-(trifluoromethyl)thiophene

HRID 1899074Notes

Reaction equation

HRID 1899074 reaction equation
Br[C:2]1[S:6][C:5]([C:7]2[CH:12]=[CH:11][C:10]([F:13])=[CH:9][CH:8]=2)=[C:4]([C:14]2[CH:19]=[CH:18][C:17]([S:20]([CH3:23])(=[O:22])=[O:21])=[CH:16][CH:15]=2)[CH:3]=1.[F:24][C:25]([F:30])([F:29])C([O-])=O.[Na+].ClCCl.Cl>CN(C)C(=O)C.O>[F:13][C:10]1[CH:11]=[CH:12][C:7]([C:5]2[S:6][C:2]([C:25]([F:30])([F:29])[F:24])=[CH:3][C:4]=2[C:14]2[CH:19]=[CH:18][C:17]([S:20]([CH3:23])(=[O:22])=[O:21])=[CH:16][CH:15]=2)=[CH:8][CH:9]=1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 31775-Bromo-2-(4-fluorophenyl)-3-(4-(methylsulfonyl)phenyl)thiopheneHCID 6344DichloromethaneHCID 517019Sodium Trifluoroacetate

Product 1

HCID 99308472-(4-Fluorophenyl)-3-[4-(methylsulfonyl)phenyl]-5-(trifluoromethyl)thiopheneYield 14.8%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 31374DimethylacetamideSolvent

Procedure

A mixture of 5-bromo-2-(4-fluorophenyl)-3-[4(methylsulfonyl)phenyl]thiophene (7.2 g), sodium trifluoroacetate (9.4 g) and cuprous iodide (6.5 g) in N,N-dimethylacetamide (109 ml), was stirred and refluxed for 5 hours. Dichloromethane (200 ml), 3N hydrochloric acid (100 ml) and water (100 ml) were added to the reaction mixture. The resulting mixture was filtered, and the filtrate was separated. The organic layer was washed with water, dried over magnesium sulfate and concentrated. The residue (13.9 g) was purified by column chromatography on silica gel eluting with a mixture of toluene and ethyl acetate (50:1). The crude product (1.3 g) was recrystallized from ethanol to give pale brown crystal of 2-(4-fluorophenyl)-3-[4-(methylsulfonyl)phenyl]-5-(trifluoromethyl)thiophene (1.04 g).

Workup

  1. temperaturerefluxed for 5 hours
  2. filtrationThe resulting mixture was filtered
  3. customthe filtrate was separated
  4. washThe organic layer was washed with water
  5. dry with materialdried over magnesium sulfate
  6. concentrationconcentrated
  7. customThe residue (13.9 g) was purified by column chromatography on silica gel eluting with a mixture of toluene and ethyl acetate (50:1)
  8. customThe crude product (1.3 g) was recrystallized from ethanol

Sources & evidence

ORD record
ord-5c4183304c0e4bfcb4c7037a3fc4612b
Source dataset
uspto-grants-1996_11
Patent number
US05571810

Reaction notes

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