2-Bromopyridine → 2-(2-fluorophenyl)pyridine

HRID 1061766Notes

Reaction equation

HRID 1061766 reaction equation
Br[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][N:3]=1.[F:8][C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=1B(O)O.C(=O)([O-])[O-].[Na+].[Na+]>C1COCC1>[F:8][C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=1[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][N:3]=1

Participants

5

Reactant 3

HCID 79732-BromopyridineHCID 10340Sodium CarbonateHCID 27343542-Fluorophenylboronic acid

Product 1

HCID 98555982-(2-fluorophenyl)pyridine

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A mixture of 2-bromopyridine (6.37 g, 35 mmol), 2-fluorobenzeneboronic acid (6.86 g, 49 mmol) and 2 M sodium carbonate solution (35 mL, 70 mmol) in THF (70 mL) was degassed with nitrogen for 20 min. Tetrakis(triphenyl-phosphine)palladium(0) (1.21 g, 1.1 mmol) was added, and the mixture was stirred at reflux under nitrogen for 36 h. After cooling to room temperature, the mixture was partitioned between ethyl acetate and sodium carbonate. The organic phase was washed with water and then with saturated sodium hydrogencarbonate solution, was dried over magnesium sulfate and then was absorbed on to silica gel. Purification by flash chromatography on silica gel, eluting with isohexane (+0.5% triethylamine and 0.5% MeOH) on a gradient of diethyl ether (5% to 20%) afforded 2-(2-fluorophenyl)pyridine as a yellow oil which crystallised upon standing (5.5 g, 91%). δH (400 MHz, CDCl3) 7.13-7.19 (1H, m), 7.24-7.28 (2H, m), 7.35-7.41 (1H, m), 7.73-7.81 (2H, m), 7.97 (1H, ddd, J 8, 8 and 2), 8.72-8.74 (1H, m); m/z (ES+) 174 (M++H).

Workup

  1. customwas degassed with nitrogen for 20 min
  2. temperatureat reflux under nitrogen for 36 h
  3. customthe mixture was partitioned between ethyl acetate and sodium carbonate
  4. washThe organic phase was washed with water
  5. dry with materialwith saturated sodium hydrogencarbonate solution, was dried over magnesium sulfate
  6. customwas absorbed on to silica gel
  7. customPurification by flash chromatography on silica gel
  8. washeluting with isohexane (+0.5% triethylamine and 0.5% MeOH) on a gradient of diethyl ether (5% to 20%)

Sources & evidence

ORD record
ord-4f854b4903634c58ab6bac39e5b285e8
Source dataset
uspto-grants-2005_11
Patent number
US06960598B2

Reaction notes

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