Toluene → 2,3,5,6-Tetrafluoro-biphenyl-4-carboxylic acid methyl ester

HRID 1470617Notes

Reaction equation

HRID 1470617 reaction equation
[C:1]1(C)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C(=O)([O-])[O-].[Cs+].[Cs+].[CH3:14][O:15][C:16](=[O:28])[C:17]1[C:22]([F:23])=[C:21]([F:24])[C:20](Br)=[C:19]([F:26])[C:18]=1[F:27].C1(B(O)O)C=CC=CC=1>O>[CH3:14][O:15][C:16]([C:17]1[C:22]([F:23])=[C:21]([F:24])[C:20]([C:1]2[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=2)=[C:19]([F:26])[C:18]=1[F:27])=[O:28]

Participants

6

Reactant 4

HCID 1140TolueneHCID 10796Cesium carbonateHCID 66827Phenylboronic AcidHCID 46311226Methyl 4-bromo-2,3,5,6-tetrafluorobenzoate

Product 1

HCID 580739182,3,5,6-Tetrafluoro-biphenyl-4-carboxylic acid methyl esterYield 88.6%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

A mixture of toluene (370 mL) and water (70 mL) was degassed with nitrogen for 30 minutes. A mixture of cesium carbonate (102.6 g, 315 mmol), 4-bromo-2,3,5,6-tetrafluoro-benzoic acid methyl ester (30.0 g, 105 mmol), phenyl boronic acid (19.26 g, 157 mmol) and tetrakis triphenyl phosphene palladium(0) (11.5 g, 9.9 mmol) were added to the above degassed water/toluene mixture. The reaction mixture was refluxed overnight. After the reaction is completed, it was cooled to room temperature and extracted with ethyl acetate. The combined organic layers were dried over sodium sulphate and concentrated. The resulting residue was purified by column chromatography using 5% ethyl acetate in hexane to obtain the title compound (26.5 g, 88.6%).

Workup

  1. customwas degassed with nitrogen for 30 minutes
  2. additionwere added to the
  3. customabove degassed water/toluene mixture
  4. temperatureThe reaction mixture was refluxed overnight
  5. extractionextracted with ethyl acetate
  6. dry with materialThe combined organic layers were dried over sodium sulphate
  7. concentrationconcentrated
  8. customThe resulting residue was purified by column chromatography

Sources & evidence

ORD record
ord-b9e058e0debc455fb0bd61a0364344ed
Source dataset
uspto-grants-2015_04
Patent number
US09006454B2

Reaction notes

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