tert-Butyl 3-allyl-4-oxopyrrolidine-1-carboxylate

1374334-11-8

120871-73-0

Step 1, Method B: Synthesis of tert-butyl 3-pentyl-4-oxopyrrolidine-1-carboxylate. Tert-butyl 3-methyl-4-oxopyrrolidine-1,3-dicarboxylate (48.65 g, 0.20 mol) was dissolved in anhydrous toluene (800 mL) and allyl alcohol (300 mL) and dibutyltin oxide (5.0 g, 20 mmol) were added. The reaction was refluxed in a Dean-Stark manifold for 20 hours, during which time the azeotrope was removed 6 hours after the start of the reaction (200 mL total) and replenished with allyl alcohol (75 mL). Upon completion of the reaction, the reaction mixture was concentrated, and the residue was dissolved in a minimal volume of dichloromethane and purified by silica gel column chromatography (700 mL v/v), eluting sequentially with dichloromethane, 10% ethyl acetate/dichloromethane, 15% ethyl acetate/dichloromethane, and 20% ethyl acetate/dichloromethane to afford 3-allyl-1-tert-butyl-4-oxo-pyrrolidine-1,3-dicarboxylate (48.6 g, 90%) as a light pink oil (structure confirmed by NMR and MS). The compound (48.47 g, 0.18 mol) was dissolved in anhydrous tetrahydrofuran (200 mL), added to a stirred solution of Pd(PPh3)4 (4.16 g, 3.6 mmol) in anhydrous tetrahydrofuran (400 mL) under nitrogen protection, stirred for 4 h and concentrated. The residue was dissolved in heptane and purified by silica gel column chromatography (1000 mL v/v) eluting with 60:35:5 heptane/dichloromethane/ethyl acetate to afford tert-butyl 3-allyl-4-oxopyrrolidine-1-carboxylate (27.93 g, 69%) as a light yellow oil (structure confirmed by NMR and MS).