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