Potassium Carbonate → 4'-Bromo-4-ethoxy-2,3-difluoro-1,1'-biphenyl

HRID 1511479Notes

Reaction equation

HRID 1511479 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].[Br:15][C:16]1[CH:21]=[CH:20][C:19](I)=[CH:18][CH:17]=1.C(=O)([O-])[O-].[K+].[K+]>Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.C1(C)C=CC=CC=1.O>[CH2:1]([O:3][C:4]1[CH:9]=[CH:8][C:7]([C:19]2[CH:20]=[CH:21][C:16]([Br:15])=[CH:17][CH:18]=2)=[C:6]([F:13])[C:5]=1[F:14])[CH3:2]

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 115221-Bromo-4-iodobenzeneHCID 15135235B-(4-Ethoxy-2,3-difluorophenyl)boronic acid

Product 1

HCID 120674514'-Bromo-4-ethoxy-2,3-difluoro-1,1'-biphenylYield 94%

Reagents, catalysts & solvents 3

HCID 178418476HCID 178418476, compoundCatalystHCID 962WaterSolvent2×HCID 1140TolueneSolvent2×

Conditions

Temperature
25 °C

Procedure

4-Ethoxy-2,3-difluorophenylboronic acid (7) (14.4 g), 4-bromoiodobenzene (8) (20.0 g), potassium carbonate (29.3 g), Pd(Ph3P)2Cl2 (1.49 g), toluene (100 ml), Solmix A-11 (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 separate into organic and aqueous phases. The extraction into an organic phase was carried out. The organic phase obtained was washed with water and dried over anhydrous magnesium sulfate. Then, the solution 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 (Solmix A-11), giving 20.8 g of 4-ethoxy-4′-bromo-2,3-difluoro-1,1′-biphenyl (9). The yield based on the compound (8) was 94.0%.

Workup

  1. temperatureheated
  2. temperatureunder reflux for 2 hours
  3. additionmixed
  4. customto separate into organic and aqueous phases
  5. extractionThe extraction into an organic phase
  6. customThe organic phase obtained
  7. washwas washed with water
  8. dry with materialdried over anhydrous magnesium sulfate
  9. concentrationThen, the solution was concentrated under reduced pressure
  10. customthe residue obtained
  11. customwas purified by means of column chromatography (silica gel; toluene)
  12. customThe product was further purified by means of recrystallization (Solmix A-11)

Sources & evidence

ORD record
ord-c1248874aae4490ea8a3e4a93107aba7
Source dataset
uspto-grants-2012_07
Patent number
US08216489B2

Reaction notes

Loading…