Potassium Carbonate → Ethyl 4-ethoxy-2,3-difluoro-4'-biphenylcarboxylate

HRID 1511477Notes

Reaction equation

HRID 1511477 reaction equation
ICC[C:4]1[CH:14]=[CH:13][C:7]([C:8]([O:10][CH2:11][CH3:12])=[O:9])=[CH:6][CH:5]=1.[CH2:15]([O:17][C:18]1[CH:23]=[CH:22][C:21](B(O)O)=[C:20]([F:27])[C:19]=1[F:28])[CH3:16].C(=O)([O-])[O-].[K+].[K+]>[Pd].C1(C)C=CC=CC=1.O.C(O)C>[CH2:15]([O:17][C:18]1[CH:23]=[CH:22][C:21]([C:4]2[CH:14]=[CH:13][C:7]([C:8]([O:10][CH2:11][CH3:12])=[O:9])=[CH:6][CH:5]=2)=[C:20]([F:27])[C:19]=1[F:28])[CH3:16]

Participants

8

Reactant 3

HCID 11430Potassium CarbonateHCID 15135235B-(4-Ethoxy-2,3-difluorophenyl)boronic acidHCID 66963157Ethyl 4-iodoethylbenzoate

Product 1

HCID 66962505Ethyl 4-ethoxy-2,3-difluoro-4'-biphenylcarboxylateYield 74.7%

Reagents, catalysts & solvents 4

HCID 23938PalladiumCatalystHCID 702EthanolSolventHCID 962WaterSolvent2×HCID 1140TolueneSolvent2×

Conditions

Temperature
25 °C

Procedure

Ethyl 4-iodoethylbenzoate (1) (25.0 g), 4-ethoxy-2,3-difluorophenylboronic acid (2) (20.1 g), potassium carbonate (25.0 g), Pd/C (0.25 g), toluene (100 ml), ethanol (100 ml) and water (100 ml) were put in a reaction vessel under a nitrogen atmosphere, and heated under reflux for 2 hours. The reaction mixture was cooled to 25° C., and then poured into water (500 ml) and toluene (500 ml), and mixed. The mixture was then allowed to stand until it had separated into two phases of organic and aqueous phases. The extraction to an organic phase was carried out. The organic phase obtained was washed with water, and then dried over anhydrous magnesium sulfate. The solution obtained was concentrated under reduced pressure, and the residue obtained was purified by means of column chromatography (silica gel; toluene). The product was further purified by means of recrystallization from ethanol and dried, giving 18.8 g of ethyl 4-ethoxy-2,3-difluoro-4′-biphenylcarboxylate (3). The yield based on the compound (1) was 67.9%.

Workup

  1. temperatureheated
  2. temperatureunder reflux for 2 hours
  3. additionmixed
  4. customhad separated into two phases of organic and aqueous phases
  5. extractionThe extraction to an organic phase
  6. customThe organic phase obtained
  7. washwas washed with water
  8. dry with materialdried over anhydrous magnesium sulfate
  9. customThe solution obtained
  10. concentrationwas concentrated under reduced pressure
  11. customthe residue obtained
  12. customwas purified by means of column chromatography (silica gel; toluene)
  13. customThe product was further purified by means of recrystallization from ethanol
  14. customdried

Sources & evidence

ORD record
ord-2e055dfe50b24da982e00080b7d70ade
Source dataset
uspto-grants-2012_07
Patent number
US08216489B2

Reaction notes

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