Potassium Carbonate → 2-Chloro-3'-fluoro-5-methoxy-1,1'-biphenyl

HRID 1473539Notes

Reaction equation

HRID 1473539 reaction equation
Br[C:2]1[CH:3]=[C:4]([O:9][CH3:10])[CH:5]=[CH:6][C:7]=1[Cl:8].[F:11][C:12]1[CH:13]=[C:14](B(O)O)[CH:15]=[CH:16][CH:17]=1.C(=O)([O-])[O-].[K+].[K+]>>[Cl:8][C:7]1[CH:6]=[CH:5][C:4]([O:9][CH3:10])=[CH:3][C:2]=1[C:16]1[CH:15]=[CH:14][CH:13]=[C:12]([F:11])[CH:17]=1

Participants

4

Reactant 3

HCID 11430Potassium CarbonateHCID 27339863-Fluorophenylboronic acidHCID 242120812-Bromo-1-chloro-4-methoxybenzene

Product 1

HCID 866875982-Chloro-3'-fluoro-5-methoxy-1,1'-biphenyl

Procedure

A round-bottom flask was charged with 3-bromo-4-chloroanisole (1.625 ml, 7.34 mmol), (3-fluorophenyl)boronic acid (1.129 g, 8.07 mmol), potassium carbonate (3.04 g, 22.01 mmol), and tetrakistriphenylphosphine palladium (0) (0.424 g, 0.367 mmol). The flask was flushed with Ar (g), then 1,4-dioxane (19.57 ml) and water (4.89 ml) were added. A reflux condenser was attached, and the flask was lowered into a 90° C. heating bath. After 2 h, the mixture was cooled, diluted with ethyl acetate, and washed with brine. The organic layer was dried over sodium sulfate, filtered, and concentrated. The residue was purified by chromatography on silica gel (80-g Redi-Sep Gold column, 0-10% EtOAc/Heptane) to give an oily solid as product that was used directly in the next step. m/z (ESI) 281.1 (M+H)+.

Workup

  1. customThe flask was flushed with Ar (g)
  2. addition1,4-dioxane (19.57 ml) and water (4.89 ml) were added
  3. customA reflux condenser was attached
  4. customwas lowered into a 90° C.
  5. temperatureheating bath
  6. temperaturethe mixture was cooled
  7. additiondiluted with ethyl acetate
  8. washwashed with brine
  9. dry with materialThe organic layer was dried over sodium sulfate
  10. filtrationfiltered
  11. concentrationconcentrated
  12. customThe residue was purified by chromatography on silica gel (80-g Redi-Sep Gold column, 0-10% EtOAc/Heptane)
  13. customto give an oily solid as product that

Sources & evidence

ORD record
ord-d7fa44edf0584bbcaca747d7356376f5
Source dataset
uspto-grants-2015_04
Patent number
US09012443B2

Reaction notes

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