2-Bromo-1-fluoro-4-nitrobenzene → 2-Fluoro-2'-methylthio-5-nitrobiphenyl

HRID 586271

Reaction equation

HRID 586271 reaction equation
Br[C:2]1[CH:7]=[C:6]([N+:8]([O-:10])=[O:9])[CH:5]=[CH:4][C:3]=1[F:11].[CH3:12][S:13][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=1B(O)O.[F-].[K+].C(P(C(C)(C)C)C(C)(C)C)(C)(C)C>C1COCC1.O1CCOCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[F:11][C:3]1[CH:4]=[CH:5][C:6]([N+:8]([O-:10])=[O:9])=[CH:7][C:2]=1[C:15]1[CH:16]=[CH:17][CH:18]=[CH:19][C:14]=1[S:13][CH3:12]

Participants

8

Reactant 4

HCID 696992-Bromo-1-fluoro-4-nitrobenzeneHCID 83681Tris(1,1-dimethylethyl)phosphineHCID 522689Potassium FluorideHCID 27735432-(Methylthio)benzeneboronic acid

Product 1

HCID 222852772-Fluoro-2'-methylthio-5-nitrobiphenylYield 99%

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 8028TetrahydrofuranSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
50 °C

Procedure

A mixture of 2-bromo-1-fluoro-4-nitrobenzene (5.89 g, 26.8 mmol), 2-(methylthio)benzeneboronic acid (5.62 g, 33.5 mmol) and potassium fluoride (5.13 g, 88.3 mmol) in THF (70 ml) was degassed with nitrogen for 30 min. This mixture was then treated with tris(dibenzylideneacetone)dipalladium(0) (496 mg, 0.541 mmol) followed by tri-tert-butylphosphine (5.35 ml of a 0.2 M solution in 1,4-dioxane, 1.07 mmol) and the reaction was degassed for a further 10 min. The resulting slurry was then heated at 50° C. for 16 h under nitrogen. After cooling, the reaction mixture was partitioned between ethyl acetate (300 ml) and water (300 ml). The organic layer was washed with saturated aqueous NaCl (200 ml), dried (Na2SO4), and evaporated. Purification by chromatography (silica gel, 5-10% EtOAc/isohexane) gave 6.95 g (99%) of the title compound as a pale yellow solid: 1H NMR (360 MHz, CDCl3) δ 2.42 (3H, s), 7.21-7.32 (3H, m), 7.37 (1H, d, J 7.4 Hz), 7.44 (1H, td, J 7.7, 1.6 Hz), 8.27-8.31 (2H, m).

Workup

  1. customwas degassed with nitrogen for 30 min
  2. customwas degassed for a further 10 min
  3. temperatureAfter cooling
  4. customthe reaction mixture was partitioned between ethyl acetate (300 ml) and water (300 ml)
  5. washThe organic layer was washed with saturated aqueous NaCl (200 ml)
  6. dry with materialdried (Na2SO4)
  7. customevaporated
  8. customPurification by chromatography (silica gel, 5-10% EtOAc/isohexane)

Sources & evidence

ORD record
ord-6e1be896244947258f62a193cfeb7f7a
Source dataset
uspto-grants-2005_08
Patent number
US06936608B2

Linked notes

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