Trifluoroacetic acid → N-[4-cyano-3-(trifluoromethyl)phenyl]piperidin-4-amine

HRID 1772194Notes

Reaction equation

HRID 1772194 reaction equation
[C:1]([C:3]1[CH:8]=[CH:7][C:6]([NH:9][CH:10]2[CH2:15][CH2:14][N:13](C(OC(C)(C)C)=O)[CH2:12][CH2:11]2)=[CH:5][C:4]=1[C:23]([F:26])([F:25])[F:24])#[N:2].FC(F)(F)C(O)=O>ClCCl>[C:1]([C:3]1[CH:8]=[CH:7][C:6]([NH:9][CH:10]2[CH2:11][CH2:12][NH:13][CH2:14][CH2:15]2)=[CH:5][C:4]=1[C:23]([F:26])([F:24])[F:25])#[N:2]

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 58576648Tert-butyl 4-[[4-cyano-3-(trifluoromethyl)phenyl]amino]piperidine-1-carboxylate

Product 1

HCID 43345818N-[4-cyano-3-(trifluoromethyl)phenyl]piperidin-4-amineYield 85%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of tert-butyl 4-[[4-cyano-3-(trifluoromethyl)phenyl]amino]piperidine-1-carboxylate (150 mg, 0.41 mmol) in dichloromethane (4 mL) was added trifluoroacetic acid (1 ml). The solution was stirred for 2 hours at room temperature and then concentrated under vacuum. The crude material was diluted with 100 ml of EtOAc and washed with sodium bicarbonate (saturated aqueous) and then brine. The organic layer was dried over anhydrous sodium sulfate, filtered, and concentrated under vacuum. The crude solids were recrystallized from EtOAc/PE to afford N-[4-cyano-3-(trifluoromethyl)phenyl]piperidin-4-amine as a yellow powder (93.1 mg, 85% yield); (ES, m/z): [M+H]+ 270.1; 1H NMR (300 MHz, CDCl3): δ 7.69 (d, J=8.7 Hz, 1H), 7.16 (d, J=7.8 Hz, 1H), 7.03 (d, J=1.2 Hz, 1H), 6.85 (dd, J=2.1, 8.7 Hz, 1H), 3.42 (m, 1H), 2.94 (m, 2H), 2.53 (m, 2H), 1.82 (d, J=10.2 Hz, 2H), 1.27 (m, 2H).

Workup

  1. concentrationconcentrated under vacuum
  2. additionThe crude material was diluted with 100 ml of EtOAc
  3. washwashed with sodium bicarbonate (saturated aqueous)
  4. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated under vacuum
  7. customThe crude solids were recrystallized from EtOAc/PE

Sources & evidence

ORD record
ord-5391b39c16284f9da840462ae724ae60
Source dataset
uspto-grants-2016_02
Patent number
US09249102B2

Reaction notes

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