4-Fluorobiphenyl → Methyl 4-(4'-fluoro-4-biphenylyl)-4-oxo-butyrate

HRID 1979138Notes

Reaction equation

HRID 1979138 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]([CH2:22][CH2:23][C:24](Cl)=[O:25])([O:20][CH3:21])=[O:19]>ClCCl>[F:5][C:6]1[CH:7]=[CH:8][C:9]([C:12]2[CH:17]=[CH:16][C:15]([C:24](=[O:25])[CH2:23][CH2:22][C:18]([O:20][CH3:21])=[O:19])=[CH:14][CH:13]=2)=[CH:10][CH:11]=1

Participants

5

Reactant 3

HCID 94614-FluorobiphenylHCID 73888Butanoic acid, 4-chloro-4-oxo-, methyl esterHCID 6451240Aluminum(III) Chloride

Product 1

HCID 15541120Methyl 4-(4'-fluoro-4-biphenylyl)-4-oxo-butyrateYield 74.6%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent3×

Procedure

To a stirred suspension of anhydrous aluminum chloride (9.64 g, 0.0723 mol) in dichloromethane (90 mL) at 5° C. was added dropwise a solution of 4-fluorobiphenyl (4.97 g, 0.0289 mol) in dichloromethane (40 mL) followed by the dropwise addition of a solution of 3-carbomethoxypropionyl chloride (3.94 mL, 0.032 mol) in dichloromethane (30 mL), and the mixture stirred. After 2 hours at 5° C., the mixture was allowed to warm to room temperature. After 1 day, the reaction was cooled to 5° C. and quenched by the dropwise addition of water (160 mL). The layers were separated, and the organic layer washed with brine, dried (Na2SO4), and rotary evaporated. The residue was recrystallized from methanol (300 mL) to give 6.17 g of 4-(4′-fluoro-biphenyl-4-yl)-4-oxo-butyric acid, methyl ester as a pale yellow solid; mp 131.5-133.0° C.

Workup

  1. waitAfter 1 day
  2. temperaturethe reaction was cooled to 5° C.
  3. customquenched by the dropwise addition of water (160 mL)
  4. customThe layers were separated
  5. washthe organic layer washed with brine
  6. dry with materialdried (Na2SO4), and rotary evaporated
  7. customThe residue was recrystallized from methanol (300 mL)

Sources & evidence

ORD record
ord-14199a152b0c45b5ab70a79f3b629dd4
Source dataset
uspto-grants-2001_05
Patent number
US06239288B1

Reaction notes

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