Potassium Phosphate, Tribasic → 2'-Fluoro-2-formyl-5'-methoxy-biphenyl-4-carboxylic acid methyl ester

HRID 404381Notes

Reaction equation

HRID 404381 reaction equation
[CH:1]([C:3]1[CH:4]=[C:5]([CH:10]=[CH:11][C:12]=1OS(C(F)(F)F)(=O)=O)[C:6]([O:8][CH3:9])=[O:7])=[O:2].[F:21][C:22]1[CH:27]=[CH:26][C:25]([O:28][CH3:29])=[CH:24][C:23]=1B(O)O.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH3:9][O:8][C:6]([C:5]1[CH:10]=[CH:11][C:12]([C:23]2[CH:24]=[C:25]([O:28][CH3:29])[CH:26]=[CH:27][C:22]=2[F:21])=[C:3]([CH:1]=[O:2])[CH:4]=1)=[O:7]

Participants

5

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 41572112-Fluoro-5-methoxyphenylboronic acidHCID 57467631Methyl 3-formyl-4-(trifluoromethylsulfonyloxy)benzoate

Product 1

HCID 574676302'-Fluoro-2-formyl-5'-methoxy-biphenyl-4-carboxylic acid methyl esterYield 100.6%

Reagents, catalysts & solvents 1

HCID 178418397HCID 178418397, compoundCatalyst

Conditions

Temperature
90 °C

Procedure

To a round bottle flask, was added methyl 3-formyl-4-(trifluoromethylsulfonyloxy)benzoate (6300 mg, 20 mmol), 2-fluoro-5-methoxyphenylboronic acid (10 g, 61 mmol), potassium phosphate tribasic (6.6 mL, 81 mmol) (granular) and tetrakis(triphenylphosphine)palladium (2.3 g, 2.0 mmol). The flask was flushed with nitrogen and then 40 mL of DME was added. The resulting mixture was then heated at 90° C. for 6 hours. The reaction mixture was diluted with EtOAc and water. The organic phase was washed with water and brine and then dried over anhydrous sodium sulfate. After filtration, the organic solvent was removed in vacuo to give a residue which was purified by CombiFlash® chromatography to give a yellow solid (5.80 g, 100%). MS ESI m/e: 289.2 (M+H)+.

Workup

  1. customThe flask was flushed with nitrogen
  2. addition40 mL of DME was added
  3. additionThe reaction mixture was diluted with EtOAc and water
  4. washThe organic phase was washed with water and brine
  5. dry with materialdried over anhydrous sodium sulfate
  6. filtrationAfter filtration
  7. customthe organic solvent was removed in vacuo
  8. customto give a residue which
  9. customwas purified by CombiFlash® chromatography

Sources & evidence

ORD record
ord-ea679f24b21e4940a472ef79b73047b5
Source dataset
uspto-grants-2014_06
Patent number
US08748462B2

Reaction notes

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