Ethanol → Ethyl 4-ethoxy-2,3-difluoro-4'-biphenylbenzoate

HRID 1943541Notes

Reaction equation

HRID 1943541 reaction equation
[CH2:1]([O:3][C:4]1[CH:9]=[CH:8][C:7](B(O)O)=[C:6]([F:13])[C:5]=1[F:14])[CH3:2].[C:15](=[O:18])([O-])[O-:16].[K+].[K+].[CH2:21](O)[CH3:22].[C:24]1([CH3:30])[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1>[Pd].O>[CH2:1]([O:3][C:4]1[CH:9]=[CH:8][C:7]([C:27]2[CH:28]=[CH:29][C:24]([C:30]3[C:8]([C:15]([O:16][CH2:21][CH3:22])=[O:18])=[CH:9][CH:4]=[CH:5][CH:6]=3)=[CH:25][CH:26]=2)=[C:6]([F:13])[C:5]=1[F:14])[CH3:2]

Participants

7

Reactant 4

HCID 702EthanolHCID 1140Toluene2×HCID 11430Potassium CarbonateHCID 15135235B-(4-Ethoxy-2,3-difluorophenyl)boronic acid

Product 1

HCID 66682456Ethyl 4-ethoxy-2,3-difluoro-4'-biphenylbenzoate

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalyst3×HCID 962WaterSolvent2×

Conditions

Temperature
25 °C

Procedure

4-Iodoethyl benzoate (1) (25.0 g), 4-ethoxy-2,3-difluorophenylboronic acid (2) (20.1 g), potassium carbonate (25.0 g), palladium on carbon (NX type of 5% Pd/C; 50% wet; made by N. E. Chemcat; hereinafter referred to as 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, and extraction into an organic phase was carried out. The organic phase obtained was fractionated, washed with water, and then dried over anhydrous magnesium sulfate. The solution obtained was concentrated under reduced pressure, and the residue obtained was purified with a fractional operation by means of column chromatography using toluene as the eluent and silica gel as the stationary phase powder. 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′-biphenylbenzoate (3). The yield based on the compound (1) was 67.9%.

Workup

  1. customwere put in a reaction vessel under a nitrogen atmosphere
  2. temperatureheated
  3. temperatureunder reflux for 2 hours
  4. additionmixed
  5. customhad separated into two phases of organic and
  6. extractionaqueous phases, and extraction into an organic phase
  7. customThe organic phase obtained
  8. washwashed with water
  9. dry with materialdried over anhydrous magnesium sulfate
  10. customThe solution obtained
  11. concentrationwas concentrated under reduced pressure
  12. customthe residue obtained
  13. customwas purified with a fractional operation by means of column chromatography
  14. customThe product was further purified by means of recrystallization from ethanol
  15. customdried

Sources & evidence

ORD record
ord-9c9948191d9d41d4bfde856cb0ef4f1b
Source dataset
uspto-grants-2013_03
Patent number
US08394294B2

Reaction notes

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