A solution of 2-(4-chlorophenoxy)benzylamine (AMR01076, 100 mg, 0.428 mmol) and 1-(3-methylbutyryl)piperidin-4-one (78.4 mg, 0.428 mmol) in DCE (5 mL) was treated with NaBH(OAc)3 (127 mg, 0.60 mmol) and acetic acid (26 mg, 0.428 mmol). The mixture was stirred at room temperature under a N2 atmosphere until TLC showed that the reactants were consumed (30 min). Then, it was quenched with saturated NaHCO3 solution, the aqueous layer was washed with DCM (2×20 mL), and the combined organic layers were dried (MgSO4), filtered and evaporated to dryness. Column chromatography on silica gel of the crude product using DCM to DCM/MeOH 95:5 gradient as eluent gave 1-{4-[2-(4-chlorophenoxy)benzylamino]piperidin-1-yl}-3-methylbutan-1-one (114 mg, 66%) as a colorless oil. Rf: 0.4 (DCM/MeOH 9:1) LC/MS (APCI) tr=5.36 min, m/z 403.46 (35), 401.44 (M++H, 100). HPLC tr=3.39 min (96.55%) 1H NMR (270 MHz, CDCl3) δ 0.92 (6H, d, J=6.4 Hz, 2CH3), 1.23 (2H, m, CH2), 1.46 (br s, NH), 1.82 (2H, br d, J=12.9 Hz, CH2), 2.05 (1H, hept, J=6.4 Hz, CHMe2), 2.19 (2H, m, CH2), 2.65 (2H, m, CH2), 2.99 (1H, m, CHNH), 3.77 (1H, m, ½CH2), 3.79 (2H, s, CH2NH), 4.40 (1H, br d, J=13.3 Hz, ½CH2), 6.81-6.87 (3H, m, ArH), 7.11 (1H, td, ArH), 7.19-7.25 (3H, m, ArH) and 7.38 (1H, dd, J=7.2, 1.5 Hz, ArH). 13C NMR (270 MHz, CDCl3) δ 22.80 (CH2), 22.90 (CH3), 25.93 (CH), 32.30, 33.15, 40.23, 42.24, 44.44, 45.65 (CH2), 53.87 (CH), 118.93, 119.62, 124.54, 127.94, 128.71, 129.83, 130.58, 131.79, 154.34, 156.37 (ArC), and 170.91 (C═O).
