Sodium Carbonate → Ethyl 2-ethyl-5-[4-(trifluoromethyl)phenyl]thiophene-3-carboxylate

HRID 1876988Notes

Reaction equation

HRID 1876988 reaction equation
Br[C:2]1[S:6][C:5]([CH2:7][CH3:8])=[C:4]([C:9]([O:11][CH2:12][CH3:13])=[O:10])[CH:3]=1.[F:14][C:15]([F:26])([F:25])[C:16]1[CH:21]=[CH:20][C:19](B(O)O)=[CH:18][CH:17]=1.C(=O)([O-])[O-].[Na+].[Na+].[Cl-].[NH4+]>C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].ClCCl.CN(C)C=O.O>[CH2:7]([C:5]1[S:6][C:2]([C:19]2[CH:20]=[CH:21][C:16]([C:15]([F:26])([F:25])[F:14])=[CH:17][CH:18]=2)=[CH:3][C:4]=1[C:9]([O:11][CH2:12][CH3:13])=[O:10])[CH3:8]

Participants

9

Reactant 4

HCID 10340Sodium CarbonateHCID 25517Ammonium ChlorideHCID 27343894-(Trifluoromethyl)phenylboronic acidHCID 68515411Ethyl 5-bromo-2-ethylthiophene-3-carboxylate

Product 1

HCID 68509779Ethyl 2-ethyl-5-[4-(trifluoromethyl)phenyl]thiophene-3-carboxylateYield 90.1%

Reagents, catalysts & solvents 4

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
80 °C

Procedure

To a mixture of ethyl 5-bromo-2-ethylthiophene-3-carboxylate (4.61 g) synthesized above, 4-(trifluoromethyl)phenylboronic acid (5.00 g), sodium carbonate (3.71 g), water (20 mL) and N,N-dimethylformamide (100 mL) was added [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II).dichloromethane adduct (1.43 g). The reaction mixture was deaerated, and stirred under an argon atmosphere at 80° C. for 2 hr. Saturated aqueous ammonium chloride solution was added to quench the reaction, and the mixture was extracted with ethyl acetate. The extract was washed with saturated sodium hydrogen carbonate and brine, dried over magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate:hexane=1:19, volume ratio) to give the title compound (5.18 g, 90%) as a white solid.

Workup

  1. customto quench
  2. customthe reaction
  3. extractionthe mixture was extracted with ethyl acetate
  4. washThe extract was washed with saturated sodium hydrogen carbonate and brine
  5. dry with materialdried over magnesium sulfate
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified by silica gel column chromatography (ethyl acetate:hexane=1:19, volume ratio)

Sources & evidence

ORD record
ord-f52c1d6ac1374c50bddc299c092e319c
Source dataset
uspto-grants-2012_11
Patent number
US08309580B2

Reaction notes

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