Potassium Carbonate → HCID 86687643, compound

HRID 1473582Notes

Reaction equation

HRID 1473582 reaction equation
[Br:1][C:2]1[CH:7]=[CH:6][C:5](I)=[CH:4][C:3]=1[O:9][CH3:10].[F:11][C:12]1[CH:13]=[C:14](B(O)O)[CH:15]=[C:16]([F:18])[CH:17]=1.C(=O)([O-])[O-].[K+].[K+]>C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].C(Cl)Cl>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([C:14]2[CH:13]=[C:12]([F:11])[CH:17]=[C:16]([F:18])[CH:15]=2)=[CH:4][C:3]=1[O:9][CH3:10]

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 2734338(3,5-Difluorophenyl)boronic acidHCID 121872021-Bromo-4-iodo-2-methoxybenzene

Product 1

HCID 86687643HCID 86687643, compound

Reagents, catalysts & solvents 1

HCID 178418807HCID 178418807, compoundCatalyst

Procedure

A round-bottom flask was charged with 1-bromo-4-iodo-2-methoxybenzene (Combi-Blocks, Inc., San Diego, Calif., 6.25 g, 19.97 mmol), (3,5-difluorophenyl)boronic acid (3.47 g, 21.97 mmol), potassium carbonate (8.28 g, 59.9 mmol), and PdCl2(dppf)-CH2Cl2 (0.816 g, 0.999 mmol). The flask was flushed with Ar (g), then 1,4-dioxane (30.0 ml) and water (9.99 ml) were added in sequence. The mixture was stirred at room temperature for 4 h. The reaction mixture was diluted with water and extracted with EtOAc (3×). The combined organic extracts were dried over sodium sulfate, filtered, and concentrated. The residue was taken up in DCM and loaded onto a pre-equilibrated 340-g SNAP Ultra column. The column was eluted with 0-10% EtOAc/Heptane containing 5% DCM. Fractions containing the desired product were combined and concentrated. The residue was taken up in heptane and filtered. The collected solid was washed with heptane (3×), then dried under a stream of N2 (g). The process was repeated with the filtrate to give a second crop of material. The two crops were dried under vacuum to give 4-bromo-3′,5′-difluoro-3-methoxy-1,1′-biphenyl as a white solid. 1H NMR (400 MHz, DMSO-d6) δ=7.66 (d, J=8.2 Hz, 1H), 7.58-7.49 (m, 2H), 7.40 (d, J=1.9 Hz, 1H), 7.33-7.20 (m, 2H), 3.96 (s, 3H). m/z (ESI) 301.1.

Workup

  1. customThe flask was flushed with Ar (g)
  2. addition1,4-dioxane (30.0 ml) and water (9.99 ml) were added in sequence
  3. additionThe reaction mixture was diluted with water
  4. extractionextracted with EtOAc (3×)
  5. dry with materialThe combined organic extracts were dried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. washThe column was eluted with 0-10% EtOAc/Heptane containing 5% DCM
  9. additionFractions containing the desired product
  10. concentrationconcentrated
  11. filtrationfiltered
  12. washThe collected solid was washed with heptane (3×)
  13. dry with materialdried under a stream of N2 (g)
  14. customto give a second crop of material
  15. customThe two crops were dried under vacuum

Sources & evidence

ORD record
ord-2add8a59678f4ce5858cd655276ee6af
Source dataset
uspto-grants-2015_04
Patent number
US09012443B2

Reaction notes

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