Iodobenzene → 4-Bromo-3-phenylpyridine

HRID 2093681Notes

Reaction equation

HRID 2093681 reaction equation
Cl.[Br:2][C:3]1[CH:8]=[CH:7][N:6]=[CH:5][CH:4]=1.[Li+].CC([N-]C(C)C)C.I[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1>C1COCC1.[Cl-].[NH4+].[Cl-].[Cl-].[Zn+2].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:2][C:3]1[CH:8]=[CH:7][N:6]=[CH:5][C:4]=1[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1

Participants

8

Reactant 3

HCID 11575IodobenzeneHCID 881004-Bromopyridinium chlorideHCID 2724682Lithium diisopropylamide

Product 1

HCID 27629394-Bromo-3-phenylpyridineYield 153.7%

Reagents, catalysts & solvents 4

HCID 3007855ZincchlorideCatalystHCID 178418397HCID 178418397, compoundCatalystHCID 8028TetrahydrofuranSolvent3×HCID 25517Ammonium ChlorideSolvent

Conditions

Temperature
-78 °C

Procedure

4-bromopyridine hydrochloride (1-BA-2, 1 g, 5.14 mmol) was dissolved in 5.1 mL of THF and the resulting solution was cooled to −78° C. LDA (10.28 mL of a 1 M solution in THF) was added over 10 minutes and the reaction mixture became brown. After stirring for 30 minutes, ZnCl2 (10.3 mL of a 0.5 M solution in THF) was added over 10 minutes and the resulting mixture was stirred for 10 minutes and then allowed to warm to rt. Iodobenzene (0.229 mL, 2.06 mmol) and Pd(PPh3)4 (593 mg, 0.514 mmol) were added and the resulting mixture was stirred under reflux for 2 h. The reaction mixture was diluted with aqueous saturated ammonium chloride and extracted with ethyl acetate. The organic phase was dried over Na2SO4 and evaporated. The residue was purified by silica column (hexane:EtOAc) to give 4-bromo-3-phenylpyridine (2-BA-2, 741 mg, 62%); LCMS: 234.0 m/z (M+H)+.

Workup

  1. stirringthe resulting mixture was stirred for 10 minutes
  2. temperatureto warm to rt
  3. stirringthe resulting mixture was stirred
  4. temperatureunder reflux for 2 h
  5. extractionextracted with ethyl acetate
  6. dry with materialThe organic phase was dried over Na2SO4
  7. customevaporated
  8. customThe residue was purified by silica column (hexane:EtOAc)

Sources & evidence

ORD record
ord-d77f41837dcb4607a31a26e25917d47b
Source dataset
uspto-grants-2013_05
Patent number
US08445503B2

Reaction notes

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