反应详情

Analogous to the procedure described for Example 1A, Step A, tetrahydro-pyrrolizine-3,5-dione (2 g, 14 mmol) was reacted with 3-chlorobenzylmagnesium chloride (0.25M in Et2O, 62 mL, 15.5 mmol) over 2 h. Purification by medium pressure chromatography eluting with a solvent gradient (2:1 hexanes:EtOAc to EtOAc to 5% MeOH in CH2Cl2) provided 5-[4-(3-chloro-phenyl)-3-oxo-butyl]-pyrrolidin-2-one (1.9142 g). 1H NMR (CDCl3) δ7.27 (m, 2H), 7.19 (m, 1H), 7.08 (m, 1H), 6.27 (br, 1H), 3.68 (s, 2H), 3.60 (m, 1H), 2.52 (t, 2H), 2.29 (m, 2H), 2.21 (m, 1H), 1.88-1.60 (m, 3H); MS 266.2 (M+1), 264.2 (M−1).

1. customPurification by medium pressure chromatography
2. washeluting with a solvent gradient (2:1 hexanes:EtOAc to EtOAc to 5% MeOH in CH2Cl2)