Potassium Hydroxide → 3-(4-Methylpiperazin-1-YL)-5-(trifluoromethyl)aniline

HRID 1640163Notes

Reaction equation

HRID 1640163 reaction equation
CC1[N:3]([C:8]2[CH:9]=[C:10]([N:18]3[CH2:23][CH2:22][N:21]([CH3:24])[CH2:20][CH2:19]3)[CH:11]=[C:12]([C:14]([F:17])([F:16])[F:15])[CH:13]=2)C(C)=CC=1.[OH-].[K+].Cl.NO>CCO.O>[CH3:24][N:21]1[CH2:20][CH2:19][N:18]([C:10]2[CH:9]=[C:8]([CH:13]=[C:12]([C:14]([F:17])([F:15])[F:16])[CH:11]=2)[NH2:3])[CH2:23][CH2:22]1

Participants

6

Reactant 3

HCID 14797Potassium HydroxideHCID 443297Hydroxyamine hydrochlorideHCID 58902457HCID 58902457, compound

Product 1

HCID 185430443-(4-Methylpiperazin-1-YL)-5-(trifluoromethyl)anilineYield 73.3%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 962WaterSolvent

Procedure

To a mixture of 1-[3-(2,5-dimethyl-1H-pyrrol-1-yl)-5-(trifluoromethyl)phenyl]-4-methylpiperazine (440 mg, 1.3 mmol) and potassium hydroxide (1.46 g, 26. mmol) in EtOH (10 mL) and water (3 mL) was added hydroxylamine hydrochloride (2.72 g, 39 mmol. The reaction mixture was heated at reflux overnight. The reaction mixture was then concentrated and the residue was dissolved in water and EtOAc. The reaction mixture was extracted with EtOAc. The organic solutions were combined, washed with brine, dried over Na2SO4 filtered and concentrated. The residue was purified by column chromatography to give 3-(4-methylpiperazin-1-yl)-5-(trifluoromethyl)aniline (247 mg, 73%) as a yellow oil. 1H NMR (300 MHz, CDCl3) δ: 6.55 (d, 1H), 6.40 (d, 1H), 6.33 (d, 1H), 3.24 (t, 4H), 2.61 (t, 4H), and 2.38 (s, 3H). LCMS: (FA) ES+ 260.2.

Workup

  1. temperatureThe reaction mixture was heated
  2. temperatureat reflux overnight
  3. concentrationThe reaction mixture was then concentrated
  4. dissolutionthe residue was dissolved in water
  5. extractionThe reaction mixture was extracted with EtOAc
  6. washwashed with brine
  7. dry with materialdried over Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe residue was purified by column chromatography

Sources & evidence

ORD record
ord-f3493cec472e415b869a1c544c5eb413
Source dataset
uspto-grants-2012_02
Patent number
US08110687B2

Reaction notes

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