HCID 19420477, compound → 1-(4-Pyridyl)piperazine

HRID 260900Notes

Reaction equation

HRID 260900 reaction equation
Cl.Br.[N:3]1[CH:8]=[CH:7][C:6]([N:9]2[CH2:14][CH2:13][NH:12][CH2:11][CH2:10]2)=[CH:5][CH:4]=1>[OH-].[Na+]>[N:3]1[CH:8]=[CH:7][C:6]([N:9]2[CH2:10][CH2:11][NH:12][CH2:13][CH2:14]2)=[CH:5][CH:4]=1

Participants

3

Reactant 1

HCID 19420477HCID 19420477, compound

Product 1

HCID 705171-(4-Pyridyl)piperazineYield 77.4%

Reagents, catalysts & solvents 1

HCID 14798Sodium HydroxideSolvent

Procedure

4-Bromopyridine hydrochloride (2.25 g, 11.61 mmol) and piparazine (5 g, 58.05 mmol) were dissolved in 10 mL of absolute ethanol and replaced into a sealed tube. It was kept in 95° C. oil bath for 5 hours and allowed to stand at room temperature for one over night. The white precipitate was filtered off, washed with a small amount of cold ethanol, and the filtrate was concentrated in vacuo to obtain 1-[4-pyridyl]piperazine hydrobromide hydrochloride salt with a contamination of unreacted piperazine. MS m/z M+H=165. H1 -NMR (in CDCl3) δ=2.95 (m, 4H), 3.36 (t, 4H), 6.82 (2H, aromatic), 8.10 (2H, aromatic). The obtained 1-[4-pyridyl]piperazine hydrobromide hydrochloride salt (1.0 g) was dissolved in 50 mL of 3N sodium hydroxide aqueous solution and stirred at room temperature for 15 minutes. The product was extracted with ethyl acetate (50 mL×3) and the combined ethyl acetate layer was washed with brine (50 mL×2), dried over anhydrous sodium sulfate. The solvent was removed in vacuo to obtain 450 mg of 1-[4-pyridyl]piperazine in 77% yield. MS m/z M+H=165. H1 -NMR (in CDCl3) δ=3.00 (m, 4H), 3.30 (t, 4H), 6.65 (2H, aromatic), 8.25 (2H, aromatic). Following the procedure of Example 6, but replacing 1-benzylpiperazine with 1-[4-pyridyl]piperazine, provides the desired compound. The product of Example 3 (2.1 g, 2.03 mmol), 1-[4-pyridyl]piperazine (999 mg, 6.09 mmol), and triethylamine (0.85 mL, 6.09 mmol) in 10 mL of methylene chloride are used. The obtained product (1.2 g, 1.13 mmol) is treated with 48%-HF (4 mL) in 35 mL of acetonitrile in the procedure described in Example 5 to yield the pure title compound.

Workup

  1. extractionThe product was extracted with ethyl acetate (50 mL×3)
  2. washthe combined ethyl acetate layer was washed with brine (50 mL×2)
  3. dry with materialdried over anhydrous sodium sulfate
  4. customThe solvent was removed in vacuo

Sources & evidence

ORD record
ord-2d492dc9bcca4373aa01c15f9d1e0572
Source dataset
uspto-grants-1996_06
Patent number
US05530119

Reaction notes

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