HCID 19420475, compound → 58198-49-5

HRID 260896Notes

Reaction equation

HRID 260896 reaction equation
Br.[N+:2]([C:5]1[CH:17]=[CH:16][C:8]([CH2:9][N:10]2[CH2:15][CH2:14][NH:13][CH2:12][CH2:11]2)=[CH:7][CH:6]=1)([O-:4])=[O:3]>[OH-].[Na+]>[N+:2]([C:5]1[CH:17]=[CH:16][C:8]([CH2:9][N:10]2[CH2:15][CH2:14][NH:13][CH2:12][CH2:11]2)=[CH:7][CH:6]=1)([O-:4])=[O:3]

Participants

3

Reactant 1

HCID 19420475HCID 19420475, compound

Product 1

HCID 9398258198-49-5Yield 78%

Reagents, catalysts & solvents 1

HCID 14798Sodium HydroxideSolvent

Procedure

Following the procedure of Example 6, but replacing 1-benzylpiperazine with 1-[4-nitrobenzyl]piperazine, provided the desired compound. To a solution of piperazine (2 g, 0.023 mol) in 10 mL of ethanol added a solution of 4-nitrobenzyl bromide (5 g, 0.023 mol) in 20 mL of warm ethanol. It was gently refluxed for 1 hour and stirred at room temperature for one over night. The resulting white precipitate was filtered, washed with a small amount of cold ethanol, and dried to yield 1-[4-nitrobenzyl]piperazine hydrobromide (3 g). MS m/z M+H=222, H1 -NMR (in MeOH-d4) δ=2.7 (t, 4H, piperazine), 3.25 (t, 4H, piperazine), 3.75 (s, 2H, benzyl), 7.62 (d, 2H, aromatic), 8.20 (d, 2H, aromatic). The obtained 1-[4-nitrobenzyl]piperazine hydrobromide (3 g, 9.93 mmol) was dissolved in 60 mL of 3N sodium hydroxide aqueous solution and stirred at room temperature for 30 minutes. The product was extracted with ethyl acetate (50 mL×3), and the combined ethyl acetate layer was washed with brine, dried over anhydrous sodium sulfate. Solvent was removed to obtain 1.7 g of 1-[4-nitrobenzyl]piperazine in 78% yield. MS m/z M+H=222, H1 -NMR (in MeOH-d4) δ2.45 (t, 4H, piperazine), 2.90 (t, 4H, piperazine), 3.55 (s, 2H, benzyl), 7.52 (d, 2H, aromatic), 8.50 (d, 2H, aromatic). The product of Example 3 (2.1 g, 2.03 mmol), 1-[4-nitrobenzyl]piperazine (1.7 g, 8.1 mmol), and triethylamine (0.85 mL, 6.09 mmol) in 10 mL of methylene chloride were used. The reaction was carried out at 45° C. for 15 hours. 1.07 g of semi-pure compound was isolated in 48% yield. MS (FAB) m/z: M+K=1147. M+H=1109. The obtained product (1.0 g, 0.9 mmol) was treated with 48%-HF (4 mL) in 30 mL of acetonitrile in the procedure described in Example 5, except stirred at 45° C. for 3 hours. 554 mg of the pure title compound was isolated in 50% yield after RP-HPLC. MS (FAB) m/z: M+K=1033. M+H=996. mp=113° C. (dec.)

Workup

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

Sources & evidence

ORD record
ord-2ff25b02e9c444b583ddfe9f37b8903a
Source dataset
uspto-grants-1996_06
Patent number
US05530119

Reaction notes

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