1-Bromo-4-fluorobenzene → HCID 57671288, compound

HRID 1013824Notes

Reaction equation

HRID 1013824 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4](B2OC(C)(C)C(C)(C)O2)[CH:5]=[C:6]([Cl:9])[C:7]=1[CH3:8].Br[C:20]1[CH:25]=[CH:24][C:23]([F:26])=[CH:22][CH:21]=1.C(=O)([O-])[O-].[K+].[K+]>COCCOC.CC([O-])=O.CC([O-])=O.[Pd+2].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.O.COC(C)(C)C>[Cl:9][C:6]1[CH:5]=[C:4]([C:20]2[CH:25]=[CH:24][C:23]([F:26])=[CH:22][CH:21]=2)[CH:3]=[C:2]([Cl:1])[C:7]=1[CH3:8]

Participants

9

Reactant 3

HCID 99931-Bromo-4-fluorobenzeneHCID 11430Potassium CarbonateHCID 532171642-(3,5-Dichloro-4-methylphenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane

Product 1

HCID 57671288HCID 57671288, compoundYield 87.7%

Reagents, catalysts & solvents 5

HCID 11776TriphenylphosphineCatalystHCID 167845palladium(II) acetateCatalystHCID 962WaterSolvent3×HCID 80711,2-DimethoxyethaneSolventHCID 15413tert-Butyl methyl etherSolvent

Conditions

Temperature
80 °C

Procedure

Step 2) To a suspension of 2-(3,5-Dichloro-4-methyl-phenyl)-4,4,5,5-tetramethyl-[1,3,2]dioxaborolane (119 g; 414.64 mmoles) in 1,2-dimethoxyethane (240 mL) under nitrogen, add p-bromofluorobenzene (57 mL; 518.54 mmoles), water (120 mL), potassium carbonate (115.7 g; 828.79 mmoles), triphenylphosphine (2.72 g; 10.37 mmoles) and Pd(OAc)2 (0.47 g; 2.09 mmoles). Heat the mixture at 80° C. for 12 h and then allow to cool to room temperature. To the mixture, add 240 mL of t-butyl methyl ether and 480 mL of water, and then separate the layers. Wash the organic layer with an aqueous solution of TMT (Trithiocyanuric acid, trisodium salt hydrate, 5 g) in 120 mL, followed by saturated aqueous NaCl (120 mL). Solvent exchange the organic layer into approximately 600 mL of isopropanol to afford a slurry. Add water (120 mL) and cool the slurry to 3° C. Collect the solid by filtration and wash with 120 mL of cold methanol. Dry the solid under vacuum to afford 92.8 g of 3,5-dichloro-4′-fluoro-4-methyl-biphenyl as a light yellow solid. 1H NMR (CDCl3, 500 MHz) δ 2.49 (3H, s), 7.13 (2H, t, J=9 Hz), 7.46 (2H, s), 7.49 (2H, dd, J=9, 5 Hz).

Workup

  1. temperatureto cool to room temperature
  2. customseparate the layers
  3. washWash the organic layer with an aqueous solution of TMT (Trithiocyanuric acid, trisodium salt hydrate, 5 g) in 120 mL
  4. customSolvent exchange the organic layer into approximately 600 mL of isopropanol to afford a slurry
  5. customCollect the solid
  6. filtrationby filtration
  7. washwash with 120 mL of cold methanol
  8. customDry the solid under vacuum

Sources & evidence

ORD record
ord-571b3b06bafb449482bb0cb48110d4c5
Source dataset
uspto-grants-2011_07
Patent number
US07981918B2

Reaction notes

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