Methane → HCID 57671288, compound

HRID 1013825Notes

Reaction equation

HRID 1013825 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+].C>C(O)(C)C.O.C(O)C.CC([O-])=O.CC([O-])=O.[Pd+2].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[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

10

Reactant 4

HCID 297MethaneHCID 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 86%

Reagents, catalysts & solvents 5

HCID 11776TriphenylphosphineCatalystHCID 167845palladium(II) acetateCatalystHCID 702EthanolSolventHCID 962WaterSolvent2×HCID 3776IsopropanolSolvent

Procedure

Alternate Step 2) Stir a slurry of 2-(3,5-dichloro-4-methyl-phenyl)-4,4,5,5-tetramethyl-[1,3,2]dioxaborolane (300 g, 1.05 moles) in 2 L of isopropanol under a blanket of nitrogen. Add p-bromofluorobenzene 61619 (150 mL; 1.36 moles) followed by an aqueous solution of potassium carbonate (160.5 g; 1.15 moles) in 300 mL water. Rinse the addition funnel with 400 mL isopropanol. Add triphenylphosphine (12.3 g; 46.89 mmoles) and Pd(OAc)2 (2.35 g; 10.47 mmoles) and heat the mixture at 75° C. for 8 h. Add water (300 mL) and allow the mixture to cool to room temperature to afford a slurry. Cool the slurry in an ice bath, collect the solid by filtration and rinse with 350 mL of 6:1 IPA-water. Dry the solid in a vacuum oven at room temperature overnight to afford 345 g of crude product. Suspend the crude product in 2.2 L of ethanol and heat at 70° C. to afford a solution. Add Darco (35 g) and stir for 30 min. Filter the mixture through a pad of Hyflo (Celite) and allow the solution to cool to room temperature to afford a slurry. Cool the slurry to 5° C., collect the solid by filtration, and rinse with cold ethanol (530 mL). Dry the solid under vacuum to afford 230 g of 3,5-dichloro-4′-fluoro-4-methyl-biphenyl as an off-white solid (86% yield).

Workup

  1. washRinse the addition funnel with 400 mL isopropanol
  2. customto afford a slurry
  3. temperatureCool the slurry in an ice bath
  4. customcollect the solid
  5. filtrationby filtration
  6. washrinse with 350 mL of 6:1 IPA-water
  7. customDry the solid in a vacuum oven at room temperature overnight
  8. customto afford 345 g of crude product
  9. temperatureheat at 70° C.
  10. customto afford a solution
  11. filtrationFilter the mixture through a pad of Hyflo (Celite)
  12. temperatureto cool to room temperature
  13. customto afford a slurry
  14. temperatureCool the slurry to 5° C.
  15. customcollect the solid
  16. filtrationby filtration
  17. washrinse with cold ethanol (530 mL)
  18. customDry the solid under vacuum

Sources & evidence

ORD record
ord-53f0b45be3ef48c5a8a7f5caf4086e5b
Source dataset
uspto-grants-2011_07
Patent number
US07981918B2

Reaction notes

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