反应详情

温度

100 °C

A solution of 2-(4-chlorophenoxy)benzylamine (AMR01073, 100 mg, 0.428 mmol), 1-acetylpiperidone (121 mg, 0.856 mmol) and acetic acid (0.13 mL, 2.14 mmol) in DCE (2 mL) was treated with NaBH(OAc)3 (227 mg, 1.07 mmol) and stirred under microwave irradiation for 15 min at 100° C. The reaction mixture was diluted with DCM (10 mL) and 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 AcOEt to AcOEt/MeOH 9:1 gradient as eluent gave 1-{4-[2-(4-chlorophenoxy)benzylamino]piperidin-1-yl}ethanone (124 mg, 81%) as a colorless oil. Rf: 0.14 (AcOEt/MeOH 9:1) LC/MS (APCI) tr=4.79 min, m/z 361.46 (35), 359.51 (M++H, 100). HPLC tr=3.04 min (97.37%) 1H NMR (270 MHz, CDCl3) δ 1.25 (2H, m, CH2), 1.68 (br s, NH), 1.79 (2H, m, CH2), 2.05 (3H, S, CH3), 2.67 (2H, m, CH2), 3.02 (1H, m, CH), 3.70 (1H, m, ½CH2), 3.82 (2H, s, CH2), 4.33 (1H, m, ½CH2), 6.84 (2H, AA′BB′, ArH), 6.86 (1H, m, ArH), 7.11 (1H, m, ArH), 7.21 (1H, m, ArH), 7.24 (2H, AA′BB′, ArH) and 7.38 (1H, dd, J=7.2, 1.5 Hz, ArH). 13C NMR (270 MHz, CDCl3) δ 21.10 (CH3), 31.49, 32.32, 39.64, 44.47, 45.05 (CH2), 53.21 (CH), 118.49, 119.04, 124.04, 127.51, 128.30, 129.36, 130.14, 131.02, 153.89, 155.80 (ArC), and 168.42 (C═O).

1. customquenched with saturated NaHCO3 solution
2. washThe aqueous layer was washed with DCM (2×20 mL)
3. dry with materialthe combined organic layers were dried (MgSO4)
4. filtrationfiltered
5. customevaporated to dryness