Acetyl chloride → 4-(4-Fluorophenyl)benzoic acid

HRID 2407470Notes

Reaction equation

HRID 2407470 reaction equation
[Cl-].[Al+3].[Cl-].[Cl-].[F:5][C:6]1[CH:11]=[CH:10][C:9]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)=[CH:8][CH:7]=1.[C:18](Cl)(=[O:20])C.[OH-].[Na+].[Mn]([O-])(=O)(=O)=[O:25].[K+]>ClCCl>[F:5][C:6]1[CH:7]=[CH:8][C:9]([C:12]2[CH:17]=[CH:16][C:15]([C:18]([OH:20])=[O:25])=[CH:14][CH:13]=2)=[CH:10][CH:11]=1

Participants

7

Reactant 5

HCID 6367Acetyl chlorideHCID 94614-FluorobiphenylHCID 14798Sodium HydroxideHCID 516875Potassium PermanganateHCID 6451240Aluminum(III) Chloride

Product 1

HCID 27826894-(4-Fluorophenyl)benzoic acid

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Anhydrous aluminum chloride (6.0 g, 0.045 mol) is added portionwise to a mixture of 4-fluorobiphenyl (4.0 g, 0.023 mol) and acetyl chloride (4.0 g, 0.051 mol) in dichloromethane (40 mL) at 5° C. The reaction mixture is stirred for 3 hours at room temperature, then quenched with demineralized water (20 mL) and dichloromethane. The organic layer is separated and concentrated under reduced pressure. Tetrahydrofuran (40 mL) is added to the residue. An aqueous solution (12 mL) of sodium hydroxide (4.0 g, 0.1 mol) followed by potassium permanganate (4.0 g, 0.025 mol) are added. The reaction mixture is stirred overnight at room temperature and filtered through celite bed. Filtrate is concentrated, Demineralized water (20 mL) is added to the residue and pH is brought to ˜2 with 1N HCl. Aqueous layer is extracted with ethyl acetate (3×20 mL). Combined ethyl acetate layers are washed with brine (1×15 mL) and dried over sodium sulphate. Removal of ethyl acetate gives crude material which is purified by column chromatography (silica gel 230-400 mesh, ethyl acetate:n-hexane) to give 4′-fluorobiphenyl-4-carboxylic acid.

Workup

  1. customquenched with demineralized water (20 mL) and dichloromethane
  2. customThe organic layer is separated
  3. concentrationconcentrated under reduced pressure
  4. additionTetrahydrofuran (40 mL) is added to the residue
  5. additionare added
  6. stirringThe reaction mixture is stirred overnight at room temperature
  7. filtrationfiltered through celite bed
  8. concentrationFiltrate is concentrated
  9. additionDemineralized water (20 mL) is added to the residue and pH
  10. extractionAqueous layer is extracted with ethyl acetate (3×20 mL)
  11. washCombined ethyl acetate layers are washed with brine (1×15 mL)
  12. dry with materialdried over sodium sulphate
  13. customRemoval of ethyl acetate
  14. customgives crude material which
  15. customis purified by column chromatography (silica gel 230-400 mesh, ethyl acetate:n-hexane)

Sources & evidence

ORD record
ord-b3ace27140384ddbad1cf974211a913e
Source dataset
uspto-grants-2014_08
Patent number
US08809539B2

Reaction notes

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