Trifluoroacetic acid → 4-[(3,3-Difluoropyrrolidin-1-yl)methyl]piperidine

HRID 1850689Notes

Reaction equation

HRID 1850689 reaction equation
C(O)(C(F)(F)F)=O.[F:8][C:9]1([F:28])[CH2:13][CH2:12][N:11]([CH2:14][CH:15]2[CH2:20][CH2:19][N:18](C(OC(C)(C)C)=O)[CH2:17][CH2:16]2)[CH2:10]1>C(Cl)Cl>[F:28][C:9]1([F:8])[CH2:13][CH2:12][N:11]([CH2:14][CH:15]2[CH2:20][CH2:19][NH:18][CH2:17][CH2:16]2)[CH2:10]1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 86720964Tert-butyl 4-((3,3-difluoropyrrolidin-1-yl)methyl)piperidine-1-carboxylate

Product 1

HCID 686436114-[(3,3-Difluoropyrrolidin-1-yl)methyl]piperidineYield 84%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

TFA (766.5 mg, 517.9 μL, 6.722 mmol) was added to a stirred solution of tert-butyl 4-[(3,3-difluoropyrrolidin-1-yl)methyl]piperidine-1-carboxylate (2.046 g, 6.722 mmol) in DCM (15 mL) and the reaction stirred at ambient temperature for 66 hours. The solvent was removed in vacuo and the residue azeotroped with DCM (×2) and ether (×2). The residue was passed through a 50 g SCX-2 cartridge and washed with MeOH/DCM mixtures. The product was eluted by washing the cartridge with 2M NH3 in MeOH/DCM mixtures. The solvent was removed in vacuo to give the sub-title compound as a pale yellow solid (1.15 g, 84% Yield). 1H NMR (500 MHz, DMSO) δ 2.89 (dt, 2H), 2.82 (t, 2H), 2.64 (t, 2H), 2.42 (td, 2H), 2.32-2.09 (m, 4H), 1.67-1.58 (m, 2H), 1.52-1.44 (m, 1H), 0.95 (dtd, 2H); 19F NMR (471 MHz, DMSO) δ −90.80; LC-MS ES+: 205.1.

Workup

  1. customThe solvent was removed in vacuo
  2. customthe residue azeotroped with DCM (×2) and ether (×2)
  3. washwashed with MeOH/DCM
  4. washThe product was eluted
  5. washby washing the cartridge with 2M NH3 in MeOH/DCM mixtures
  6. customThe solvent was removed in vacuo

Sources & evidence

ORD record
ord-a9d4955d372942b4a02397d3867172d6
Source dataset
uspto-grants-2015_02
Patent number
US08957078B2

Reaction notes

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