2-Bromo-1-fluoro-4-nitrobenzene → HCID 22285303, compound

HRID 586258Notes

Reaction equation

HRID 586258 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].C([Sn](CCCC)(CCCC)[C:17]1[CH:22]=[CH:21][N:20]=[CH:19][CH:18]=1)CCC.[Cl-].[Li+]>CN(C)C(=O)C.[Cu]I.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[F:11][C:3]1[CH:4]=[CH:5][C:6]([N+:8]([O-:10])=[O:9])=[CH:7][C:2]=1[C:17]1[CH:22]=[CH:21][N:20]=[CH:19][CH:18]=1

Participants

7

Reactant 3

HCID 696992-Bromo-1-fluoro-4-nitrobenzeneHCID 433294Lithium ChlorideHCID 27373184-(Tri-n-butylstannyl)pyridine

Product 1

HCID 22285303HCID 22285303, compoundYield 88%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418397HCID 178418397, compoundCatalystHCID 31374DimethylacetamideSolvent

Conditions

Temperature
80 °C

Procedure

To a degassed solution of 2-bromo-1-fluoro-4-nitrobenzene (A. Groweiss, Org. Process Res. Dev., 2000, 4, 30-33) (6.44 g, 29.3 mmol), 4-tri-n-butylstannylpyridine (14.0 g, 38.0 mmol), lithium chloride (12.4 g, 293 mmol) and copper(I) iodide (0.56 g, 2.93 mmol) in N,N-dimethylacetamide (40 ml) was added tetrakis(triphenylphosphine)palladium(0) (1.69 g, 1.46 mmol) and the reaction heated at 80° C. for 18 h. After cooling to ambient temperature the solvent was evaporated and the residue was diluted with dichloromethane (800 ml) and the mixture stirred vigorously for 30 min then filtered. The organics were washed with water (500 ml) and brine (300 ml), dried (MgSO4), filtered and evaporated to give a black oil. The residue was purified by chromatography [silica gel, 20-50% EtOAc/isohexane (containing 1% methanol and 1% triethylamine)] to give 4-(2-fluoro-5-nitrophenyl)pyridine as an off-white solid (5.60 g, 88%): 1H NMR (360 MHz, CDCl3) δ 7.38 (1H, t, J 9 Hz), 7.50-7.53 (2H, m), 8.30-8.35 (1H, m), 8.41-8.44 (1H, m), 8.76-8.78 (2H, m).

Workup

  1. temperatureAfter cooling to ambient temperature the solvent
  2. customwas evaporated
  3. additionthe residue was diluted with dichloromethane (800 ml)
  4. filtrationthen filtered
  5. washThe organics were washed with water (500 ml) and brine (300 ml)
  6. dry with materialdried (MgSO4)
  7. filtrationfiltered
  8. customevaporated
  9. customto give a black oil
  10. customThe residue was purified by chromatography [silica gel, 20-50% EtOAc/isohexane (containing 1% methanol and 1% triethylamine)]

Sources & evidence

ORD record
ord-ff8d875e290446e6a5d7088b8d9bc3cb
Source dataset
uspto-grants-2005_08
Patent number
US06936608B2

Reaction notes

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