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

HRID 1929249Notes

Reaction equation

HRID 1929249 reaction equation
[Br:1][C:2]1[CH:7]=[CH:6][C:5](I)=[CH:4][CH:3]=1.[CH2:9]([O:11][C:12]1[CH:17]=[CH:16][C:15](B(O)O)=[C:14]([F:21])[C:13]=1[F:22])[CH3:10].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>[CH2:9]([O:11][C:12]1[CH:17]=[CH:16][C:15]([C:5]2[CH:6]=[CH:7][C:2]([Br:1])=[CH:3][CH:4]=2)=[C:14]([F:21])[C:13]=1[F:22])[CH3:10]

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-Bromoiodobenzene (1) (20.0 g), 4-ethoxy-2,3-difluorophenylboronic acid (2) (14.4 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 stand until it had separated into two phases of organic and aqueous phases, and an extractive operation to 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 Solmix A-11 and dried, giving 20.8 g of 4-ethoxy-4′-bromo-2,3-difluoro-1,1′-biphenyl (3). The yield based on the compound (1) was 94.0%.

Workup

  1. temperatureheated
  2. temperatureunder reflux for 2 hours
  3. additionmixed
  4. customhad separated into two phases of organic and aqueous phases
  5. customThe organic phase obtained
  6. washwashed with water
  7. dry with materialdried over anhydrous magnesium sulfate
  8. customThe solution obtained
  9. concentrationwas concentrated under reduced pressure
  10. customthe residue obtained
  11. customwas purified with a fractional operation by means of column chromatography
  12. customThe product was further purified by means of recrystallization from Solmix A-11
  13. customdried

Sources & evidence

ORD record
ord-f6f6c893b69d422b9dd7dda165051522
Source dataset
uspto-grants-2012_05
Patent number
US08187494B2

Reaction notes

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