Reaction Steps
A solution of 2-(2,4-dichlorophenoxy)benzoic acid (AMR01067, 1.24 g, 4.39 mmol) in dry DCM (20 mL) was stirred under nitrogen, and 4-dimethylaminopyridine (DMPA, 40 mg, 0.327 mmol), (1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDC, 2.5, 13.18 mmol) and triethylamine (0.6 mL) were added. The resulting mixture was stirred for 30 min under nitrogen and 4-aminopiperidine-1-carboxylic acid tert-butyl ester (AMR01068, 0.88 g, 4.39 mmol) in dry DCM (410 mL) was added. After stirring at room temperature for 48 h, the mixture was diluted with DCM, washed with HCl (1M, 3×25 mL), water, saturated NaHCO3 (2×25 mL) and brine. The organic layer was dried (MgSO4), filtered and evaporated. Flash chromatography on silica gel of the crude product using DCM/MeOH 99:1 as eluenty gave 4-[2-(2,4-dichlorophenoxy)benzoylamino]piperidine-1-carboxylic acid tert-butyl ester (953 mg, 40%) as white solid. Rf: 0.64 (DCM/MeOH 9:1) 1H NMR (270 MHz, CDCl3) δ 1.48 (9H, s, 3CH3), 1.92 (2H, m, CH2), 2.92 (2H, br t, CH2), 3.95 (2H, br d, CH2), 4.11 (1H, m, CH), 6.78 (1H, dd, J=8.2, 1.0 Hz, ArH), 6.87 (1H, d, J=8.9 Hz, ArH), 7.21 (1H, dd, J=8.6, 2.5 Hz, ArH), 7.25 (1H, m, ArH), 7.35 (1H, br s, NH), 7.40 (1H, m, ArH), 7.50 (1H, d, J=2.5 Hz, ArH) and 8.17 (1H, dd, J=7.9, 2.0 Hz, ArH). LC/MS (APCI) tr=5.36 min, m/z 467.36 (18), 465.41 (M++H, 30), 411.33 (67), 409.38 (M+-C4H8, 100). HPLC tr=2.93 min (97.22%)
