Trifluoroacetic acid → 4-(2-Chlorophenoxy)piperidine

Trifluoroacetic acid (4 mL) was added to crude carbamate 10.6 (1.030 g). After 20 min at rt most of the volatiles were removed in vacuo and 1 M HCl (10 mL) was added, whereupon an oil separated. This was washed with DCM (3×3 mL). The aqueous portion was basified to pH>12 with 5 M NaOH, extracted with DCM (3×4 mL), dried (MgSO4), filtered and concentrated to an oil (10 mg). The initial DCM washing was dried (MgSO4), filtered and concentrated to a pale yellow oil (1.26 g), whose 1H NMR was consistent with being the piperidinium trifluoroacetate. This material, plus the initial collected free base (10 mg) was dissolved in ether (30 mL) and washed with 5 M NaOH (10 mL), 1 M NaOH (2×10 mfL), water (10 mL) and saturated NaCl (2×10 mL), then dried (MgSO4) and filtered. HCl—saturated ether (35 mL) was added and the turbid solution was extracted with 1 M HCl (3×10 mL). The acidic portion was basified with 5 M NaOH, extracted with DCM (3×8 mL) and the organic portion dried (MgSO4), filtered and concentrated to a pale yellow oil (457 mg; 62% from 4-hydroxypiperidine-1-carboxylic acid tert-butyl ester). LC (method B) tR=8.2 min; 1H NMR (200 MHz, CDCl3) δ 7.37 (dd, J=1.6, 8.0 Hz, 1H), 7.19 (ddd, J=1.5, 7.3, 8.6 Hz, 1H), 7.0-6.8 (m, 2H), 4.42 (tt, J=3.9, 3.9 Hz, 1H), 3.18 (ddd, J=4.0, 6.3, 12.0 Hz, 2H), 2.73 (ddd, J=3.7, 8.6, 12.3 Hz, 2H), 2.00 (m, 2H), 1.77 (m, 2H); ESIMS (free base) 212.0/213.9 (100/37) [MH+].