Trifluoroacetic acid → 4-[4-(3-Pyrrolidin-1-ylpropoxy)phenyl]piperidine-4-carbonitrile
Reaction equation
[C:1]([C:3]1([C:16]2[CH:21]=[CH:20][C:19]([O:22][CH2:23][CH2:24][CH2:25][N:26]3[CH2:30][CH2:29][CH2:28][CH2:27]3)=[CH:18][CH:17]=2)[CH2:8][CH2:7][N:6](C(OC(C)(C)C)=O)[CH2:5][CH2:4]1)#[N:2].FC(F)(F)C(O)=O>ClCCl>[N:26]1([CH2:25][CH2:24][CH2:23][O:22][C:19]2[CH:20]=[CH:21][C:16]([C:3]3([C:1]#[N:2])[CH2:4][CH2:5][NH:6][CH2:7][CH2:8]3)=[CH:17][CH:18]=2)[CH2:30][CH2:29][CH2:28][CH2:27]1Participants
4
Procedure
tert-Butyl 4-cyano-4-[4-(3-pyrrolidin-1-ylpropoxy)phenyl]piperidine-1-carboxylate (500 mg, 1.24 mmol) was stirred for 1 hour in trifluoroacetic acid (1.91 ml, 24.8 mmol) and dichloromethane (30 ml). More trifluoroacetic acid (3 ml) was added and the reaction stirred at room temperature for another hour. The reaction mixture was quenched with saturated aqueous sodium carbonate solution (15 ml) and the layers separated. The organic layer was dried over sodium sulphate and concentrated in vacuo. The crude product was purified by flash chromatography on silica gel eluting with dichloromethane:methanol:ammonia (95:5:0.5 to 90:10:1 by volume) to provide the title compound (450 mg, 18% over 2 steps). 1H NMR (400 MHz, CD3OD) δ 1.81-1.85 (m, 4H), 1.91-2.09 (m, 6H), 2.59-2.62 (m, 4H), 2.69 (t, 2H), 2.99 (t, 2H), 3.12-3.15 (m, 2H), 4.04 (t, 2H), 6.96 (d, 2H), 7.42 (d, 2H). HRMS ESI+ m/z 314.2227 [MH]+.