反应详情

A mixture of 3-(t-butoxycarbonylamino-methyl)-phthalic acid (3.3 g, 11.2 mmol) and 3-amino-3-methyl-piperidine-2,6-dione hydrochloride (2.0 g, 11.2 mmol) in pyridine (40 mL) was refluxed for 17 hours. The mixture was cooled and concentrated. The residue was dissolved in EtOAc (200 mL) and water (50 mL). The organic layer was washed with water (40 mL), Sat. NaHCO3 (40 mL), water (40 mL), and brine (40 mL), and dried (MgSO4). Solvent was removed, and the residue was purified by chromatography (Silica gel) to give [2-(3-methyl-2,6-dioxo-piperidin-3-yl)-1,3-dioxo-2,3-dihydro-1H-isoindol-4-ylmethyl]-carbamic acid t-butyl ester (2.3 g, 51%): 1H NMR (CDCl3) δ 1.43 (s, 9H, 3(CH3)), 2.08 (s, 3H, CH3), 2.10-2.15 (m, 1H), 2.69-2.84 (m, 3H), 4.62 (d, J=6.5 Hz, 2H, CH2), 5.46 (m, 1H, NH), 7.64-7.76 (m, 3H, Ar), 8.15 (s, 1H, NH).

1. temperaturewas refluxed for 17 hours
2. temperatureThe mixture was cooled
3. concentrationconcentrated
4. dissolutionThe residue was dissolved in EtOAc (200 mL)
5. washThe organic layer was washed with water (40 mL), Sat. NaHCO3 (40 mL), water (40 mL), and brine (40 mL)
6. dry with materialdried (MgSO4)
7. customSolvent was removed
8. customthe residue was purified by chromatography (Silica gel)