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

HRID 1504469Notes

Reaction equation

HRID 1504469 reaction equation
Br[C:2]1[CH:7]=[C:6]([O:8][CH3:9])[CH:5]=[C:4]([F:10])[CH:3]=1.[Cl:11][C:12]1[CH:13]=[C:14](B(O)O)[CH:15]=[CH:16][CH:17]=1.C(=O)([O-])[O-].[K+].[K+]>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[Cl:11][C:12]1[CH:17]=[C:16]([C:2]2[CH:7]=[C:6]([O:8][CH3:9])[CH:5]=[C:4]([F:10])[CH:3]=2)[CH:15]=[CH:14][CH:13]=1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 2734323(3-Chlorophenyl)boronic acidHCID 108220943-Bromo-5-fluoroanisole

Product 1

HCID 1177372123'-Chloro-3-fluoro-5-methoxy-1,1'-biphenylYield 102%

Reagents, catalysts & solvents 1

HCID 178418397HCID 178418397, compoundCatalyst

Procedure

A RBF was charged with 1-bromo-3-fluoro-5-methoxybenzene (2.104 g, 10.26 mmol), (3-chlorophenyl)boronic acid (1.765 g, 11.29 mmol), potassium carbonate (4.25 g, 30.8 mmol), and Pd(Ph3P)4 (0.593 g, 0.513 mmol). The flask was flushed with Ar (g), then 1,4-dioxane (25.7 ml) and water (8.55 ml) were added. A reflux condenser was attached, and the flask was lowered into a 90° C. heating bath for 45 min. The mixture was cooled to room temperature, diluted with water, and extracted with EtOAc (2×). The combined organic extracts were dried over sodium sulfate, filtered, and concentrated. The residue was purified by chromatography on silica gel (50-g SNAP Ultra column, 25-g silica gel column, 0-5% EtOAc/Heptane) to give 3′-chloro-3-fluoro-5-methoxy-1,1′-biphenyl (2.47 g, 10.44 mmol, 102% yield) as a clear oil containing about 10 wt % impurities.

Workup

  1. customThe flask was flushed with Ar (g)
  2. addition1,4-dioxane (25.7 ml) and water (8.55 ml) were added
  3. customA reflux condenser was attached
  4. customwas lowered into a 90° C.
  5. temperatureheating bath for 45 min
  6. additiondiluted with water
  7. extractionextracted with EtOAc (2×)
  8. dry with materialThe combined organic extracts were dried over sodium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customThe residue was purified by chromatography on silica gel (50-g SNAP Ultra column, 25-g silica gel column, 0-5% EtOAc/Heptane)

Sources & evidence

ORD record
ord-374895cbf32747ee9287aecee0f669da
Source dataset
uspto-grants-2015_12
Patent number
US09212182B2

Reaction notes

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