Ammonium formate → 4-(3,5-Bis(trifluoromethyl)phenyl)piperidine Hydrochloride

HRID 58430Notes

Reaction equation

HRID 58430 reaction equation
[ClH:1].[F:2][C:3]([F:21])([F:20])[C:4]1[CH:5]=[C:6]([C:14]2[CH2:15][CH2:16][NH:17][CH2:18][CH:19]=2)[CH:7]=[C:8]([C:10]([F:13])([F:12])[F:11])[CH:9]=1.C([O-])=O.[NH4+]>CO.[Pd]>[ClH:1].[F:21][C:3]([F:2])([F:20])[C:4]1[CH:5]=[C:6]([CH:14]2[CH2:19][CH2:18][NH:17][CH2:16][CH2:15]2)[CH:7]=[C:8]([C:10]([F:12])([F:13])[F:11])[CH:9]=1

Participants

5

Reactant 2

HCID 2723923Ammonium formateHCID 1184833804-(3,5-Bis(trifluoromethyl)phenyl)-1,2,3,6-tetrahydropyridine hydrochloride

Product 1

HCID 450739294-(3,5-Bis(trifluoromethyl)phenyl)piperidine HydrochlorideYield 82.2%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 887MethanolSolvent

Procedure

A mixture of 4-(3,5-bis(trifluoromethyl)phenyl)-1,2,3,6-tetrahydropyridine hydrochloride (19, 452 mg, 1.37 mmol), ammonium formate (0.863 g, 13.7 mmol), and 10% Pd/C (0.332 g) in CH3OH (10 mL) was heated at reflux for 7 h. The mixture was cooled to ambient temperature and was filtered over Celite. The filtrate was concentrated and the resulting residue was diluted in CH2Cl2 (8 mL) and CH3OH (2 mL). To this solution was added HCl (2.0 N solution in Et2O, 6 mL). The resulting solids were collected by filtration to give 4-(3,5-bis(trifluoromethyl)phenyl)piperidine hydrochloride (20) as a white solid (376 mg, 82%): 1H NMR (300 MHz, DMSO-d6) δ 9.05-8.58 (m, 2H), 8.03-7.97 (m, 1H), 7.95-7.87 (m, 2H), 3.44-3.29 (m, 2H, overlaps with H2O), 3.19-2.88 (m, 3H), 2.09-1.80 (m, 4H); ESI MS m/z 298 [M+H]+.

Workup

  1. temperaturewas heated
  2. temperatureat reflux for 7 h
  3. filtrationwas filtered over Celite
  4. concentrationThe filtrate was concentrated
  5. additionthe resulting residue was diluted in CH2Cl2 (8 mL)
  6. additionTo this solution was added HCl (2.0 N solution in Et2O, 6 mL)
  7. filtrationThe resulting solids were collected by filtration

Sources & evidence

ORD record
ord-fdf2b62c140b417a9eaaf091f152201b
Source dataset
uspto-grants-2016_09
Patent number
US09434727B2

Reaction notes

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