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

HRID 586267Notes

Reaction equation

HRID 586267 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 organic layer was washed with water, then saturated sodium hydrogencarbonate, dried over anhydrous magnesium sulfate, filtered and pre-adsorbed onto silica. Purification by chromatography [silica gel, 20-40% EtOAc/isohexane (containing 0.5% triethylamine)] afforded 4-(2-fluorophenyl)pyridine as a yellow oil that crystallised on standing (6.26 g, 94%): 1H NMR (400 MHz, CDCl3) δ 7.17-7.22 (1H, m), 7.26 (1H, ddd, J 8, 8, 1 Hz), 7.38-7.44 (1H, m), 7.47-7.50 (3H, m), 8.68 (2H, d, J 4 Hz); MS (ES+) m/z 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 organic layer was washed with water
  6. dry with materialsaturated sodium hydrogencarbonate, dried over anhydrous magnesium sulfate
  7. filtrationfiltered and pre-adsorbed onto silica
  8. customPurification by chromatography [silica gel, 20-40% EtOAc/isohexane (containing 0.5% triethylamine)]

Sources & evidence

ORD record
ord-d86505800a154de1a11d60824fea7e46
Source dataset
uspto-grants-2005_08
Patent number
US06936608B2

Reaction notes

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