Methanol → Methyl 3-fluoro-5-(3-fluorophenyl)-2-methyl-benzoate

HRID 1771728Notes

Reaction equation

HRID 1771728 reaction equation
Br[C:2]1[CH:7]=[C:6]([C:8]2[CH:13]=[CH:12][CH:11]=[C:10]([F:14])[CH:9]=2)[CH:5]=[C:4]([F:15])[C:3]=1[CH3:16].[C:17]([O-:20])(=[O:19])C.[K+].[C]=O.[CH3:24]O>C1COCC1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.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.[Fe+2]>[F:15][C:4]1[C:3]([CH3:16])=[C:2]([CH:7]=[C:6]([C:8]2[CH:13]=[CH:12][CH:11]=[C:10]([F:14])[CH:9]=2)[CH:5]=1)[C:17]([O:20][CH3:24])=[O:19]

Participants

8

Reactant 4

HCID 887MethanolHCID 517044Potassium AcetateHCID 894440223-Bromo-3',5-difluoro-4-methyl-1,1'-biphenylHCID 178418416HCID 178418416, compound

Product 1

HCID 89443724Methyl 3-fluoro-5-(3-fluorophenyl)-2-methyl-benzoateYield 57%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)CatalystHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
125 °C

Procedure

A mixture of 1-bromo-3-fluoro-5-(3-fluorophenyl)-2-methyl-benzene (1.88 g, 6.6 mmol, 1 eq), potassium acetate (3.25 g, 33.2 mmol, 5 eq), palladium (II) acetate (0.12 g, 0.5 mmol, 0.075 eq) and dppf (0.41 g, 0.9 mmol, 0.15 eq) in a mixture of MeOH (50 mL) and THF (50 mL) was placed in a high pressure reactor and pressurized with carbon monoxide gas to 50 bar. The reaction mixture was heated at 125° C. for 16 h, then cooled, filtered and the solvent evaporated in vacuo. The residue was partitioned between water and CH2Cl2 and extracted with CH2Cl2. The combined organic extracts were dried (MgSO4), filtered and evaporated in vacuo. The residue obtained was purified by column chromatography (petroleum ether:EtOAc 1:0 to 50:1) to give the title compound as a white solid (1 g, 57%).

Workup

  1. customwas placed in a high pressure reactor
  2. temperaturecooled
  3. filtrationfiltered
  4. customthe solvent evaporated in vacuo
  5. customThe residue was partitioned between water and CH2Cl2
  6. extractionextracted with CH2Cl2
  7. dry with materialThe combined organic extracts were dried (MgSO4)
  8. filtrationfiltered
  9. customevaporated in vacuo
  10. customThe residue obtained
  11. customwas purified by column chromatography (petroleum ether:EtOAc 1:0 to 50:1)

Sources & evidence

ORD record
ord-334e86722f9e418b828da520f3393595
Source dataset
uspto-grants-2016_02
Patent number
US09249085B2

Reaction notes

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