1-Piperazinecarboxylic acid, ethyl ester → Ethyl 4-(3-fluoro-2-pyridinyl)-1-piperazinecarboxylate

HRID 1263219Notes

Reaction equation

HRID 1263219 reaction equation
Cl[C:2]1[C:7]([F:8])=[CH:6][CH:5]=[CH:4][N:3]=1.[CH3:9][CH2:10][O:11][C:12]([N:14]1[CH2:19][CH2:18][NH:17][CH2:16][CH2:15]1)=[O:13]>C(O)CCC>[F:8][C:7]1[C:2]([N:17]2[CH2:16][CH2:15][N:14]([C:12]([O:11][CH2:10][CH3:9])=[O:13])[CH2:19][CH2:18]2)=[N:3][CH:4]=[CH:5][CH:6]=1

Participants

4

Reactant 2

HCID 84311-Piperazinecarboxylic acid, ethyl esterHCID 27827912-Chloro-3-fluoropyridine

Product 1

HCID 20455069Ethyl 4-(3-fluoro-2-pyridinyl)-1-piperazinecarboxylate

Reagents, catalysts & solvents 1

HCID 2631-ButanolSolvent

Procedure

A solution of 2-chloro-3-fluoropyridine (650 mg, 5.06 mmol) and ethyl N-piperazinocarboxylate (1.61 g, 10.2 mmol) in 60 ml of n-butanol is stirred at reflux under nitrogen for 18 hours. After concentrating to dryness under reduced pressure, the residue is dissolved in a mixture of ethyl acetate and water. The ethyl acetate extract is washed again with water, dried over anhydrous sodium sulfate, filtered and concentrated. The N-carbethoxy derivative of 1-(3-fluoro-2-pyridinyl)piperazine is further purified by chromatography over silica gel 60 (230-400 mesh).

Workup

  1. temperatureat reflux under nitrogen for 18 hours
  2. concentrationAfter concentrating to dryness under reduced pressure
  3. dissolutionthe residue is dissolved in a mixture of ethyl acetate and water
  4. extractionThe ethyl acetate extract
  5. washis washed again with water
  6. dry with materialdried over anhydrous sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe N-carbethoxy derivative of 1-(3-fluoro-2-pyridinyl)piperazine is further purified by chromatography over silica gel 60 (230-400 mesh)

Sources & evidence

ORD record
ord-0a7bbd763ec343b1ad0aa2909d106d7a
Source dataset
uspto-grants-1984_06
Patent number
US04456604

Reaction notes

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