4-Bromopyridinium chloride → 4-(2-Fluorophenyl)pyridine

HRID 1061772Notes

Reaction equation

HRID 1061772 reaction equation
Cl.Br[C:3]1[CH:8]=[CH:7][N:6]=[CH:5][CH:4]=1.[F:9][C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=1B(O)O>O1CCCC1.C(=O)([O-])[O-].[Na+].[Na+].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:9][C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=1[C:3]1[CH:8]=[CH:7][N:6]=[CH:5][CH:4]=1

Participants

6

Reactant 2

HCID 881004-Bromopyridinium chlorideHCID 27343542-Fluorophenylboronic acid

Product 1

HCID 132706464-(2-Fluorophenyl)pyridine

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 8028TetrahydrofuranSolventHCID 10340Sodium CarbonateSolvent

Procedure

A mixture of 4-bromopyridine hydrochloride (7.5 g, 38.6 mmol) and 2-fluorobenzeneboronic acid (6.75 g, 48 mmol) in tetrahydrofuran (80 mL) and 2 M sodium carbonate (58 mL) was degassed with nitrogen for 20 min then tetrakis(triphenylphosphine)palladium(0) (1.34 g, 1.2 mmol) was added and the reaction heated at reflux for 24 h. The mixture was cooled to ambient temperature then partitioned between ethyl acetate and 10% sodium carbonate. The organics were washed with water and saturated sodium hydrogencarbonate, dried over anhydrous magnesium sulfate, filtered and pre-adsorbed onto silica. Purification by chromatography on silica eluting with isohexane (containing 0.5% triethylamine) on a gradient of ethyl acetate (20-40%) afforded 4-(2-fluorophenyl)pyridine as a yellow oil that crystallised on standing (6.26 g, 94%): δH (400 MHz, CDCl3) 7.17-7.22 (1H, m), 7.26 (1H, ddd, J 8, 8 and 1), 7.38-7.44 (1H, m), 7.47-7.50 (3H, m), 8.68 (2H, d, J 4); m/z (ES+) 174 (M++H).

Workup

  1. customwas degassed with nitrogen for 20 min
  2. temperaturethe reaction heated
  3. temperatureat reflux for 24 h
  4. customthen partitioned between ethyl acetate and 10% sodium carbonate
  5. washThe organics were washed with water and saturated sodium hydrogencarbonate
  6. dry with materialdried over anhydrous magnesium sulfate
  7. filtrationfiltered and pre-adsorbed onto silica
  8. customPurification by chromatography on silica eluting with isohexane (containing 0.5% triethylamine) on a gradient of ethyl acetate (20-40%)

Sources & evidence

ORD record
ord-a68cd858c7f74569ac5f5f288b36656d
Source dataset
uspto-grants-2005_11
Patent number
US06960598B2

Reaction notes

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