Hydrochloric Acid → 2-(Piperazin-1-yl)nicotinaldehyde

HRID 845204Notes

Reaction equation

HRID 845204 reaction equation
Cl[C:2]1[C:7]([C:8]2C=CC=CC=2)=[CH:6][CH:5]=[CH:4][N:3]=1.[NH:14]1[CH2:19][CH2:18][NH:17][CH2:16][CH2:15]1.Cl.C([OH:24])(C)C>>[N:14]1([C:2]2[C:7]([CH:8]=[O:24])=[CH:6][CH:5]=[CH:4][N:3]=2)[CH2:19][CH2:18][NH:17][CH2:16][CH2:15]1

Participants

5

Reactant 4

HCID 313Hydrochloric AcidHCID 3776IsopropanolHCID 4837PiperazineHCID 27628072-Chloro-3-phenylpyridine

Product 1

HCID 201324292-(Piperazin-1-yl)nicotinaldehyde

Procedure

A solution of 2-chloro-3-pyridinecarboxaldehyde (VI; 6.4 g, 0.05 mole) and piperazine (19.4 g, 0.23 mole) was refluxed 5 hr in isopropanol (250 mL). The reaction mixture was concentrated in vacuo to a syrup which was partitioned between methylene chloride and water. The organic phase was isolated, washed with water (3×500 mL), dried (MgSO4), filtered, and concentrated in vacuo to a syrup which was flash chromatographed (10% methanol-methylene chloride). The appropriate fractions were combined, concentrated in vacuo, dissolved in ethanol and treated with 1 equivalent of ethanolic HCl. Crystallization of the crude hydrochloride salt gave 8.8 g (87%) of the appropriate IIIc intermediate.

Workup

  1. concentrationThe reaction mixture was concentrated in vacuo to a syrup which
  2. customwas partitioned between methylene chloride and water
  3. customThe organic phase was isolated
  4. washwashed with water (3×500 mL)
  5. dry with materialdried (MgSO4)
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo to a syrup which
  8. customchromatographed (10% methanol-methylene chloride)
  9. concentrationconcentrated in vacuo
  10. dissolutiondissolved in ethanol
  11. customCrystallization of the crude hydrochloride salt
  12. customgave 8.8 g (87%) of the appropriate IIIc intermediate

Sources & evidence

ORD record
ord-ebbfa632bd064d819900c8a8b05890ca
Source dataset
uspto-grants-1988_07
Patent number
US04757073

Reaction notes

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