Piperazine → Piperazine, 1-(3-fluoro-2-pyridinyl)-, hydrochloride (1:2)

HRID 325609Notes

Reaction equation

HRID 325609 reaction equation
[Cl:1][C:2]1[C:7]([F:8])=[CH:6][CH:5]=[CH:4][N:3]=1.[NH:9]1[CH2:14][CH2:13][NH:12][CH2:11][CH2:10]1>C(O)CCC>[ClH:1].[ClH:1].[F:8][C:7]1[C:2]([N:9]2[CH2:14][CH2:13][NH:12][CH2:11][CH2:10]2)=[N:3][CH:4]=[CH:5][CH:6]=1

Participants

4

Reactant 2

HCID 4837PiperazineHCID 27827912-Chloro-3-fluoropyridine

Product 1

HCID 20455072Piperazine, 1-(3-fluoro-2-pyridinyl)-, hydrochloride (1:2)Yield 35%

Reagents, catalysts & solvents 1

HCID 2631-ButanolSolvent

Procedure

A solution of 2-chloro-3-fluoropyridine (500 mg, 4.25 mmol) and anhydrous piperazine (3.66 g, 42.5 mmol) in 40 ml of n-butanol is stirred at reflux for 18 hours. After concentrating to dryness in vacuo, the residue is partitioned between toluene and dilute sodium hydroxide solution (5% w/v). The toluene layer is washed with a saturated sodium chloride solution, dried over Na2SO4, filtered and concentrated to 0.65 g of oil. Upon treatment of the oil with ethanolic hydrogen chloride and crystallization by dissolving the crude material in a minimum of methanol:ethanol (1:1) mixture and addition of ethyl acetate to incipient cloudiness, there is obtained 0.38 g., (35% yield) of product, m.p. 203°-210° C.

Workup

  1. temperatureat reflux for 18 hours
  2. concentrationAfter concentrating to dryness in vacuo
  3. customthe residue is partitioned between toluene and dilute sodium hydroxide solution (5% w/v)
  4. washThe toluene layer is washed with a saturated sodium chloride solution
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated to 0.65 g of oil
  8. customUpon treatment of the oil with ethanolic hydrogen chloride and crystallization
  9. dissolutionby dissolving the crude material
  10. additionin a minimum of methanol:ethanol (1:1) mixture and addition of ethyl acetate
  11. customthere is obtained 0.38 g

Sources & evidence

ORD record
ord-233b3158b1564ad7843eca9fb70befdb
Source dataset
uspto-grants-1984_04
Patent number
US04442103

Reaction notes

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