2-[3-(4-Methoxy-1-piperidinyl)propyl]-1H-isoindole-1,3(2H)-dione → 3-(4-Methoxypiperidin-1-yl)propan-1-amine

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Reaction Conditions

Reaction Steps

A solution of phthalimide 305 (6.0 g, 19.8 mmol) and N2H4.H2O (1.9 mL, 40 mmol) in EtOH (100 mL) was stirred at reflux temperature for 2 h. The solution was cooled to 5° C. for 2 h, the precipitate filtered, washed with EtOH (5 mL) and the filtrate evaporated to half volume. The solution was cooled at 5° C. for a further 2 h, the precipitate filtered, washed with EtOH (5 mL) and the filtrate evaporated. The residue was dissolved in 1 M HCl (50 mL), washed with Et2O (2×50 mL) and the pH of the aqueous fraction adjusted to 10 with dilute aqueous NH3 solution. The mixture was extracted with CHCl3 (4×50 mL), the combined organic fraction dried and the solvent evaporated to give diamine 306 (1.85 g, 54%) as a pale yellow oil: 1H NMR δ 3.33 (s, 3H, OCH3), 3.17-3.24 (m, 1H, CHO), 2.71-2.78 (m, 4H, 2×CH2N), 2.37 (dd, J=7.5, 7.2 Hz, 2H, CH2N), 2.08-2.13 (m, 2H, CH2N), 1.85-1.93 (m, 2H, CH2), 1.50-1.67 (m, 6H, 2×CH2, NH2); MS m/z 172 (M+, 5%), 128 (60), 57 (100); HRMS calcd for C9H20N2O (M+) m/z 172.1576, found 172.1571.

Provenance & Evidence