2,5-Dibromopyridine → 5-Bromo-2-(4-fluorophenyl)pyridine

HRID 1796049Notes

Reaction equation

HRID 1796049 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([Br:8])=[CH:4][N:3]=1.[F:9][C:10]1[CH:15]=[CH:14][C:13](B(O)O)=[CH:12][CH:11]=1>COCCOC.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>[Br:8][C:5]1[CH:6]=[CH:7][C:2]([C:13]2[CH:14]=[CH:15][C:10]([F:9])=[CH:11][CH:12]=2)=[N:3][CH:4]=1

Participants

6

Reactant 2

HCID 693532,5-DibromopyridineHCID 2856454-Fluorophenylboronic acid

Product 1

HCID 221807795-Bromo-2-(4-fluorophenyl)pyridineYield 88.4%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 80711,2-DimethoxyethaneSolventHCID 10340Sodium CarbonateSolvent

Procedure

To a degassed mixture of 2,5-dibromopyridine (500 mg, 2.11 mmol) and 4-fluorobenzeneboronic acid (444 mg, 3.17 mmol) in ethylene glycol dimethyl ether (4.2 ml) and 2M aqueous sodium carbonate (2.1 ml) was added tetrakis(triphenylphosphine)palladium(0) (98 mg, 0.08 mmol). This mixture was heated at reflux for 14 h. After cooling the crude reaction was partitioned between water and dichloromethane. The organics were dried over anhydrous magnesium sulfate, filtered and adsorbed onto silica. Purification by chromatography on silica gel, eluting with a mixture of 4% diethyl ether in isohexane, gave 5-bromo-2-(4-fluorophenyl)pyridine (470 mg) as a white solid: δH (360 MHz, CDCl3) 7.30 (1H, d, J 7), 7.12-7.19 (2H, m), 7.57 (1H, d, J 8), 7.86 (1H, dd, J 2 and 8), 7.92-7.98 (2H, m), 8.72 (1H, d, J 2), m/z (ES+) 251, 252, 253, 254 (M++H).

Workup

  1. temperatureThis mixture was heated
  2. temperatureat reflux for 14 h
  3. temperatureAfter cooling the crude
  4. customreaction
  5. customwas partitioned between water and dichloromethane
  6. dry with materialThe organics were dried over anhydrous magnesium sulfate
  7. filtrationfiltered
  8. customPurification by chromatography on silica gel
  9. washeluting with a mixture of 4% diethyl ether in isohexane

Sources & evidence

ORD record
ord-7cf2865dc7b64592a7c48a2c8e137ec7
Source dataset
uspto-grants-2006_04
Patent number
US07030128B2

Reaction notes

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