Toluene → HCID 22717512, compound

HRID 413619Notes

Reaction equation

HRID 413619 reaction equation
[Br:1][C:2]1[CH:7]=[CH:6][C:5](I)=[C:4]([F:9])[CH:3]=1.[CH2:10]([C:14]1[CH:19]=[CH:18][C:17](B(O)O)=[CH:16][CH:15]=1)[CH2:11][CH2:12][CH3:13].C1(C)C=CC=CC=1.C(=O)([O-])[O-].[Na+].[Na+]>O1CCCC1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.Cl[Pd]Cl.B.[Na].COC(C)(C)C.O.C(O)C>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([C:17]2[CH:18]=[CH:19][C:14]([CH2:10][CH2:11][CH2:12][CH3:13])=[CH:15][CH:16]=2)=[C:4]([F:9])[CH:3]=1

Participants

11

Reactant 4

HCID 1140TolueneHCID 10340Sodium CarbonateHCID 27245164-Bromo-2-fluoro-1-iodobenzeneHCID 41008604-Butylphenylboronic acid

Product 1

HCID 22717512HCID 22717512, compoundYield 89.6%

Reagents, catalysts & solvents 6

HCID 6102075Dichlorobis(triphenylphosphine)palladiumCatalystHCID 178418435HCID 178418435, compoundCatalystHCID 702EthanolSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 15413tert-Butyl methyl etherSolvent

Conditions

Temperature
55 °C

Procedure

2.106 g of bis(triphenylphosphine) palladium(II)chloride (Merck Schuchart, Art. No. 804 174) were suspended in 20.0 ml tetrahydrofurane (Merck KGaA, Art. No.108 107) in a 50 ml, four necked vessel and heated to 55° C. Now 0.113 g sodiumboric hydride (Merck Schuchart, Art. Nr. 806 372) were added slowly while the suspension was stirred with a magnetic stirrer. The dark mixture was heated under reflux for 30 minutes and then allowed to cool to 40° C. 49.648 g of 1-bromo-3-fluoro-4-iodo-benzene (Wychem, Art. No. 45 570 300/12) 35.60 g of 4-n-butyl-phenylboronic acid, prepared in house), 330 ml toluene (Merck KGaA, Art. No.108 325), 130 ml ethanol (Merck KGaA, Art. No.100 983) and 170 ml of a solution of sodium carbonate (Merck KGaA, Art. No.106 384) were placed in an 1 I, four necked vessel at ambient temperature and heated to 50° C. Now the freshly prepared 40° C. warm solution of the Pd0-catalyst was rapidly added dropwise to the vigorously stirred reaction mixture. The brown mixture was stirred at 50° C. for 16 hours. The completeness of the reaction was confirmed by thin sheet chromatography. The reaction mixture was cooled to ambient temperature. Then distilled water and methyl-t-butyl ether were added and the phases separated. The aquous phase was extracted twice with methyl-t-butyl ether. The combined organic phases were washed twice with distilled water, dried over Na2SO4 filtered and the solvent evaporated. The crude product of 74 g of 4-bromo-4′-n-butyl-2-fluoro-biphenyl was purified over 3 I silica gel with 1-chloro-butane. The resultant 61.4 g of crude product were distilled under reduced pressure. Thus 45.4 g of 4-bromo-4′-n-butyl-2-fluoro-biphenyl with a purity of 90.6% by GC were obtained.

Workup

  1. temperatureThe dark mixture was heated
  2. temperatureunder reflux for 30 minutes
  3. temperatureto cool to 40° C
  4. customwere placed in an 1 I, four necked vessel at ambient temperature
  5. temperatureheated to 50° C
  6. temperatureNow the freshly prepared 40° C. warm solution of the Pd0-catalyst
  7. additionwas rapidly added dropwise to the vigorously stirred reaction mixture
  8. stirringThe brown mixture was stirred at 50° C. for 16 hours
  9. temperatureThe reaction mixture was cooled to ambient temperature
  10. customthe phases separated
  11. extractionThe aquous phase was extracted twice with methyl-t-butyl ether
  12. washThe combined organic phases were washed twice with distilled water
  13. dry with materialdried over Na2SO4
  14. filtrationfiltered
  15. customthe solvent evaporated
  16. customThe crude product of 74 g of 4-bromo-4′-n-butyl-2-fluoro-biphenyl was purified over 3 I silica gel with 1-chloro-butane
  17. distillationThe resultant 61.4 g of crude product were distilled under reduced pressure

Sources & evidence

ORD record
ord-90a347be3f8d4b498c2013ff6c71f304
Source dataset
uspto-grants-2003_05
Patent number
US06569505B2

Reaction notes

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