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

HRID 524910Notes

Reaction equation

HRID 524910 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 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 4-((3,3-difluoropyrrolidin-1-yl)methyl)piperidine as a pale yellow solid (1.15 g, 84% Yield over 2 steps). 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-78f486f887fa49d9bf55918d5d99352c
Source dataset
uspto-grants-2016_05
Patent number
US09340546B2

Reaction notes

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