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

HRID 1886715Notes

Reaction equation

HRID 1886715 reaction equation
I[C:2]1[CH:12]=[CH:11][C:5]([C:6]([O:8][CH2:9][CH3:10])=[O:7])=[CH:4][CH:3]=1.[CH2:13]([O:15][C:16]1[CH:21]=[CH:20][C:19](B(O)O)=[C:18]([F:25])[C:17]=1[F:26])[CH3:14].C(=O)([O-])[O-].[K+].[K+]>[Pd].C1(C)C=CC=CC=1.O.C(O)C>[CH2:13]([O:15][C:16]1[CH:21]=[CH:20][C:19]([C:2]2[CH:12]=[CH:11][C:5]([C:4]3[C:5]([C:6]([O:8][CH2:9][CH3:10])=[O:7])=[CH:11][CH:12]=[CH:2][CH:3]=3)=[CH:4][CH:3]=2)=[C:18]([F:25])[C:17]=1[F:26])[CH3:14]

Participants

8

Reactant 3

HCID 11430Potassium CarbonateHCID 142891Ethyl 4-iodobenzoateHCID 15135235B-(4-Ethoxy-2,3-difluorophenyl)boronic acid

Product 1

HCID 66682456Ethyl 4-ethoxy-2,3-difluoro-4'-biphenylbenzoateYield 108.6%

Reagents, catalysts & solvents 4

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

Conditions

Temperature
25 °C

Procedure

Ethyl 4-iodobenzoate (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 added to a reaction vessel under an atmosphere of nitrogen, and heated to reflux for 2 hours. After the reaction solution had been cooled to 25° C., it was poured into water (500 ml) and toluene (500 ml), and mixed with them. The mixture was then allowed to stand until it had separated into two phases of organic and aqueous phases, and the extraction into an organic phase was carried out. The resulting organic phase was separated, and washed with water, and then dried over anhydrous magnesium sulfate. The solution was concentrated under reduced pressure, and the resulting residue was purified by column chromatography using silica gel as a stationary phase powder and toluene as an eluent. The product was further purified by recrystallization from ethanol and dried to give ethyl 4-ethoxy-2,3-difluoro-4′-biphenylbenzoate (3) (18.8 g). The yield based on the compound (1) was 67.9%.

Workup

  1. temperatureheated
  2. temperatureto reflux for 2 hours
  3. additionmixed with them
  4. customhad separated into two phases of organic and aqueous phases
  5. extractionthe extraction into an organic phase
  6. customThe resulting organic phase was separated
  7. washwashed with water
  8. dry with materialdried over anhydrous magnesium sulfate
  9. concentrationThe solution was concentrated under reduced pressure
  10. customthe resulting residue was purified by column chromatography
  11. customThe product was further purified by recrystallization from ethanol
  12. customdried

Sources & evidence

ORD record
ord-abd297a21b9d4e0aa6363476838f09de
Source dataset
uspto-grants-2013_08
Patent number
US08501038B2

Reaction notes

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