1-Bromo-4-nitrobenzene → 4-Bromo-3-(4-nitrophenyl)pyridine

HRID 1405067Notes

Reaction equation

HRID 1405067 reaction equation
[Li+].CC([N-]C(C)C)C.Cl.[Br:10][C:11]1[CH:16]=[CH:15][N:14]=[CH:13][CH:12]=1.Br[C:18]1[CH:23]=[CH:22][C:21]([N+:24]([O-:26])=[O:25])=[CH:20][CH:19]=1>C1COCC1.[Cl-].[NH4+].[Cl-].[Zn+2].[Cl-].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:10][C:11]1[CH:16]=[CH:15][N:14]=[CH:13][C:12]=1[C:18]1[CH:23]=[CH:22][C:21]([N+:24]([O-:26])=[O:25])=[CH:20][CH:19]=1

Participants

8

Reactant 3

HCID 114661-Bromo-4-nitrobenzeneHCID 881004-Bromopyridinium chlorideHCID 2724682Lithium diisopropylamide

Product 1

HCID 232466804-Bromo-3-(4-nitrophenyl)pyridineYield 39.8%

Reagents, catalysts & solvents 4

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

Procedure

A solution of LDA (2.86 mL, 5.14 mmol) in THF (2.5 mL) was transferred to a solution of 4-bromopyridine hydrochloride (500 mg, 2.57 mmol) in THF (5 mL) at −78° C. and stirred for 30 min. Zinc chloride (350 mg, 2.57 mmol) in THF (2.5 mL) was added to the above reaction mixture. A precipitate was formed and the mixture was allowed to warm to room temperature. Next, 1-bromo-4-nitrobenzene (1039 mg, 5.14 mmol) and tetrakis(triphenylphosphine)palladium(0) (149 mg, 0.129 mmol) were added, and the reaction mixture was heated to reflux for 3 hours and then cooled to room temperature. The resulting reaction mixture was diluted with saturated solution of ammonium chloride (25 mL) and extracted with EtOAc (2×25 mL). The combined organics were washed with brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The crude material was purified by silica gel chromatography (40 g ISCO column, eluting with 0% to 50% EtOAc in CH2Cl2) to afford Intermediate 13A (300 mg, 1.023 mmol, 10.47% yield) as a pale yellow solid. MS (ES): m/z=280.9 [M+H]+. 1H NMR (400 MHz, DMSO-d6) δ ppm 7.84 (s, 1 H) 7.87 (s, 1 H) 7.97 (d, J=5.29 Hz, 1 H) 8.41 (s, 1 H) 8.43 (s, 1 H) 8.57 (d, J=5.29 Hz, 1 H) 8.66 (s, 1 H).

Workup

  1. customA precipitate was formed
  2. temperaturethe reaction mixture was heated
  3. temperatureto reflux for 3 hours
  4. temperaturecooled to room temperature
  5. customThe resulting reaction mixture
  6. extractionextracted with EtOAc (2×25 mL)
  7. washThe combined organics were washed with brine
  8. dry with materialdried over anhydrous sodium sulfate
  9. concentrationconcentrated under reduced pressure
  10. customThe crude material was purified by silica gel chromatography (40 g ISCO column, eluting with 0% to 50% EtOAc in CH2Cl2)

Sources & evidence

ORD record
ord-04b76ee67b8444d6b4cc2f0a72d832d7
Source dataset
uspto-grants-2014_12
Patent number
US08916553B2

Reaction notes

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