Hydrochloric Acid → 4-(4-Fluorobenzyl)-1-(2-(4-fluorophenoxy)ethyl)piperidine hydrochloride

Reaction equation

Br.[F:2][C:3]1[CH:16]=[CH:15][C:6](C(C2CCNCC2)=O)=[CH:5][CH:4]=1.[C:17]([N:20]1[CH2:25][CH2:24][CH:23]([C:26](=O)[C:27]2[CH:32]=[CH:31][C:30]([F:33])=[CH:29][CH:28]=2)[CH2:22][CH2:21]1)(=O)[CH3:18].[OH-:35].[Na+].[ClH:37]>>[ClH:37].[F:33][C:30]1[CH:31]=[CH:32][C:27]([CH2:26][CH:23]2[CH2:24][CH2:25][N:20]([CH2:17][CH2:18][O:35][C:6]3[CH:15]=[CH:16][C:3]([F:2])=[CH:4][CH:5]=3)[CH2:21][CH2:22]2)=[CH:28][CH:29]=1

Participants

Reactant 4

HCID 313Hydrochloric Acid

HCID 14798Sodium Hydroxide

HCID 1172571-Acetyl-4-(4-fluorobenzoyl)piperidine

HCID 186215174-(p-Fluorobenzoyl)piperidine hydrobromide

Product 1

HCID 232944164-(4-Fluorobenzyl)-1-(2-(4-fluorophenoxy)ethyl)piperidine hydrochlorideYield 98%

Procedure

4-(4-Fluorobenzoyl)piperidine hydrobromide. A solution of 1-acetyl-4-(4-fluoro-benzoyl)piperidine (1.20 g, 4.80 mmol) in HCl (6N, 15 mL) was refluxed for 2 h. The cooled solution was made basic (NaOH) and then extracted with benzene (2×40 mL). The collected organic phase was washed with brine (50 mL), dried and was concentrated under reduced pressure. The free amine was dissolved in HBr (saturated solution in MeOH, 10 mL). The precipitated hydrobromide salt was collected, washed with ether (2×4 mL) and dried in vacuo to afford the title compound as a colorless solid (1.54 g, 98%): mp 198° C.; 1H NMR (CD3OD) 1.80-2.00 (m, 2H), 2.05-2.18 (m, 2H), 3.12-3.28 (m, 2H), 3.40-3.50 (m, 2H), 3.70-3.85 (m, 1H), 4.85 (s, 2H), 7.24 (t, J=8.3 Hz, 2H), 8.10 (dd, J=5.7 and 8.7 Hz, 2H).