Trifluoroacetic acid → 1-{[3-(Trifluoromethyl)phenyl]methyl}piperidin-4-amine

HRID 1258148Notes

Reaction equation

HRID 1258148 reaction equation
C(OC(=O)[NH:7][CH:8]1[CH2:13][CH2:12][NH:11][CH2:10][CH2:9]1)(C)(C)C.[F:15][C:16]([F:26])([F:25])[C:17]1[CH:18]=[C:19]([CH:22]=[CH:23][CH:24]=1)[CH2:20]Br.C(N(C(C)C)CC)(C)C.FC(F)(F)C(O)=O>ClCCl>[F:15][C:16]([F:25])([F:26])[C:17]1[CH:18]=[C:19]([CH:22]=[CH:23][CH:24]=1)[CH2:20][N:11]1[CH2:10][CH2:9][CH:8]([NH2:7])[CH2:13][CH2:12]1

Participants

6

Reactant 4

HCID 6422Trifluoroacetic acidHCID 81531DiisopropylethylamineHCID 1230611-(Bromomethyl)-3-(trifluoromethyl)benzeneHCID 7238334-(N-Boc-amino)piperidine

Product 1

HCID 128889291-{[3-(Trifluoromethyl)phenyl]methyl}piperidin-4-amineYield 65.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A mixture of piperidin-4-ylcarbamic acid tert-butyl ester (2.5 g, 12.4 mmol), 3-(trifluoromethyl)benzyl bromide (1.7 ml, 11.3 mmol) and diisoproylethylamine (2.9 ml, 16.9 mmol) in dichloromethane (25 ml) was stirred at room temperature for 2 h. After this period, trifluoroacetic acid (32 ml) was added and the reaction mixture was stirred for a further 2 h. The solvent was evaporated in vacuo and a saturated solution of sodium carbonate was added. The mixture was extracted with dichloromethane and the separated organic layers were dried (Na2SO4), filtered, and the solvent evaporated in vacuo. The residue was purified by column chromatography (silica gel; 5-10% ammonia in methanol (7 M)/dichloromethane) to yield D6 (1.9 g, 60%) as a solid. C13H12F3N2 requires 258. Found 259 (MH+)

Workup

  1. waitAfter this period
  2. stirringthe reaction mixture was stirred for a further 2 h
  3. customThe solvent was evaporated in vacuo
  4. additiona saturated solution of sodium carbonate was added
  5. extractionThe mixture was extracted with dichloromethane
  6. dry with materialthe separated organic layers were dried (Na2SO4)
  7. filtrationfiltered
  8. customthe solvent evaporated in vacuo
  9. customThe residue was purified by column chromatography (silica gel; 5-10% ammonia in methanol (7 M)/dichloromethane)

Sources & evidence

ORD record
ord-626d993e4cb54e508795554cf8d3305e
Source dataset
uspto-grants-2013_06
Patent number
US08466153B2

Reaction notes

Loading…