Piperazine → 1-[3-(Trifluoromethyl)pyridin-2-yl]piperazine

HRID 490208Notes

Reaction equation

HRID 490208 reaction equation
Cl[C:2]1[C:7]([C:8]([F:11])([F:10])[F:9])=[CH:6][CH:5]=[CH:4][N:3]=1.[NH:12]1[CH2:17][CH2:16][NH:15][CH2:14][CH2:13]1>C(O)CCC>[F:9][C:8]([F:11])([F:10])[C:7]1[C:2]([N:12]2[CH2:17][CH2:16][NH:15][CH2:14][CH2:13]2)=[N:3][CH:4]=[CH:5][CH:6]=1

Participants

4

Reactant 2

HCID 4837PiperazineHCID 5898332-Chloro-3-(trifluoromethyl)pyridine

Product 1

HCID 27777861-[3-(Trifluoromethyl)pyridin-2-yl]piperazineYield 40%

Reagents, catalysts & solvents 1

HCID 2631-ButanolSolvent

Procedure

A solution of 2-chloro-3-trifluoromethylpyridine (6.57 g, 36.2 mmol) and piperazine (31.48 g, 365.5 mmol) in n-butanol was heated to 115° C. After 48 hours, the mixture was cooled to room temperature, the solvent removed under reduced pressure and the residue partitioned between water and ethyl acetate. The organic phase was dried (sodium sulfate), filtered and concentrated under reduced pressure. The residue was purified by flash column chromatography on silica gel (elution with 15% methanol:dichloromethane) to provide 3.35 g (40% yield) of the title compound as a tan solid. 1H NMR (300 MHz, DMSO-d6) δ 2.80 (m, 4H), 3.10 (m, 4H), 7.15 (ddd, 1H, J=7.8, 4.7, 1.0 Hz), 8.03 (dd, 1H, J=7.8, 1.7 Hz), 8.50 (ddd, 1H, J=4.8, 2.0, 0.7 Hz); MS (DCI/NH3) m/e 232 (M+H)+.

Workup

  1. customthe solvent removed under reduced pressure
  2. customthe residue partitioned between water and ethyl acetate
  3. dry with materialThe organic phase was dried (sodium sulfate)
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was purified by flash column chromatography on silica gel (elution with 15% methanol:dichloromethane)

Sources & evidence

ORD record
ord-252c9e44bfed46c3bc7cd504fe13eafe
Source dataset
uspto-grants-2009_05
Patent number
US07528134B2

Reaction notes

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