Piperazine → Diethyl-4-piperazinyl-2,6-pyridinedicarboxylate

HRID 1531458Notes

Reaction equation

HRID 1531458 reaction equation
[CH2:1]([O:3][C:4]([C:6]1[CH:11]=[C:10](Br)[CH:9]=[C:8]([C:13]([O:15][CH2:16][CH3:17])=[O:14])[N:7]=1)=[O:5])[CH3:2].[NH:18]1[CH2:23][CH2:22][NH:21][CH2:20][CH2:19]1>O1CCOCC1>[OH-:3].[NH4+:7].[CH2:1]([O:3][C:4]([C:6]1[CH:11]=[C:10]([N:18]2[CH2:23][CH2:22][NH:21][CH2:20][CH2:19]2)[CH:9]=[C:8]([C:13]([O:15][CH2:16][CH3:17])=[O:14])[N:7]=1)=[O:5])[CH3:2]

Participants

5

Reactant 2

HCID 4837PiperazineHCID 13794409Diethyl 4-bromopyridine-2,6-dicarboxylate

Product 2

HCID 14923Ammonium HydroxideYield 30%HCID 85702736Diethyl-4-piperazinyl-2,6-pyridinedicarboxylateYield 198.5%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

A mixture of diethyl 4-bromopyridine-2,6-dicarboxylate (Example 49) (3.02 g, 10.0 mmol) and piperazine (Aldrich, 4.3 g, 50 mmol) in dioxane (200 mL) was refluxed for 24 hours. The precipitate was filtered off and the filtrate was concentrated under vacuum. The residue was dissolved in ethyl acetate and washed four times with brine. The organic solution was dried (Na2SO4) and the solvent was evaporated. The residue was purified by flash chromatography on a silica gel column (22 cm×3 cm). Elution with methanol and then methanol:30% ammonium hydroxide (100:1, 50:1, and 20:1, v/v) gave 3.05 g (99%) of the title compound as a pale yellow foam.

Workup

  1. temperaturewas refluxed for 24 hours
  2. filtrationThe precipitate was filtered off
  3. concentrationthe filtrate was concentrated under vacuum
  4. dissolutionThe residue was dissolved in ethyl acetate
  5. washwashed four times with brine
  6. dry with materialThe organic solution was dried (Na2SO4)
  7. customthe solvent was evaporated
  8. customThe residue was purified by flash chromatography on a silica gel column (22 cm×3 cm)
  9. washElution with methanol

Sources & evidence

ORD record
ord-4c129075f6094680b9c21fdc99594b50
Source dataset
uspto-grants-2001_03
Patent number
US06197965B1

Reaction notes

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