C(Cl)CCl.[N:5]1([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:10][CH2:9][CH:8]([C:11]([O-:13])=O)[CH2:7][CH2:6]1.Cl.[CH3:22][NH:23][O:24][CH3:25].C(N(CC)CC)C>CN(C1C=CN=CC=1)C.ClCCl.O>[C:17]([O:16][C:14]([N:5]1[CH2:6][CH2:7][CH:8]([C:11](=[O:13])[N:23]([O:24][CH3:25])[CH3:22])[CH2:9][CH2:10]1)=[O:15])([CH3:20])([CH3:19])[CH3:18]EDC (6.29 g, 32.8 mmol) was added in several portions to a stirring solution of piperidine-1,4-dicarboxylic acid, mono tert-butyl ester (5.0 g, 21.8 mmol), DMAP (10 mg), and N,O-dimethylhydroxylamine hydrochloride (3.21 g, 32.8 mmol) in dichloromethane (100 mL). To the resultant solution was added dropwise triethylamine (9.4 mL, 65.6 mmol), and the reaction mixture was stirred at room temperature overnight. The next day, the reaction mixture was poured into water, and the aqueous layer was extracted using ethyl acetate (3×). The combined organic phase was washed with saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate, filtered and concentrated in vacuo to give a colorless oil. Purification by column chromatography (silica gel, 0-40% ethyl acetate in heptane) gave tert-butyl-4-[methoxy(methyl)-carbamoyl]-piperidine-1-carboxylate (5.04 g, 85%) as a colorless oil; 1H NMR (CDCl3, 300 MHz) δ 4.16 (m, 2H), 3.70 (s, 3H), 3.17 (s, 3H), 2.72-2.86 (m, 3H), 1.62-1.75 (m, 4H) and 1.44 (s, 9H).
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