4-(5-Fluoro-2-(trifluoromethyl)phenyl)-1,2,3,6-tetrahydropyridine hydrochloride → 4-(5-Fluoro-2-(trifluoromethyl)phenyl)piperidine Hydrochloride
Reaction equation
[ClH:1].[F:2][C:3]1[CH:4]=[CH:5][C:6]([C:15]([F:18])([F:17])[F:16])=[C:7]([C:9]2[CH2:10][CH2:11][NH:12][CH2:13][CH:14]=2)[CH:8]=1>CCOC(C)=O.O=[Pt]=O>[ClH:1].[F:2][C:3]1[CH:4]=[CH:5][C:6]([C:15]([F:18])([F:16])[F:17])=[C:7]([CH:9]2[CH2:10][CH2:11][NH:12][CH2:13][CH2:14]2)[CH:8]=1Participants
Procedure
A mixture of 4-(5-fluoro-2-(trifluoromethyl)phenyl)-1,2,3,6-tetrahydropyridine hydrochloride (10, 0.393 g, 1.41 mmol) and PtO2 (0.095 mg, 0.42 mmol) in EtOAc (14 mL) was stirred at ambient temperature for 18 h under a balloon of H2. The mixture was filtered over Celite, and the filtrate was concentrated under reduced pressure and dissolved in CH2Cl2 (4 mL). To this solution was added HCl (2 N in Et2O, 4.0 mL) and the resulting mixture stirred at ambient temperature for 20 min. The resulting suspension was diluted with Et2O (20 mL) and the solids were collected by filtration to provide 4-(5-fluoro-2-(trifluoromethyl)phenyl)piperidine hydrochloride (11) as a white solid (309 mg, 78%): 1H NMR (300 MHz, DMSO-d6) δ 8.81 (br s, 2H), 7.80 (dd, J=9.3, 6.0 Hz, 1H), 7.39-7.26 (m, 2H), 3.43-3.30 (m, 1H, overlaps with H2O), 3.24-2.97 (m, 3H), 2.11-1.90 (m, 2H), 1.88-1.75 (m, 2H); ESI MS m/z 248 [M+H]+.
Workup
- filtrationThe mixture was filtered over Celite
- concentrationthe filtrate was concentrated under reduced pressure
- dissolutiondissolved in CH2Cl2 (4 mL)
- additionTo this solution was added HCl (2 N in Et2O, 4.0 mL)
- stirringthe resulting mixture stirred at ambient temperature for 20 min
- additionThe resulting suspension was diluted with Et2O (20 mL)
- filtrationthe solids were collected by filtration
Sources & evidence
- ORD record
- ord-612f62eae96b415fba804c178cb50779
- Source dataset
- uspto-grants-2016_09
- Patent number
- US09434727B2
Reaction notes
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