1779-49-3

101385-93-7

114214-71-0

Step A: Synthesis of tert-butyl 3-methylene pyrrolidine-1-carboxylate. To a suspension consisting of methyltriphenylphosphonium bromide (18 g, 51 mmol) and tetrahydrofuran (THF, 200 mL) was slowly added n-butyllithium (1.6 M hexane solution, 32 mL) at 0 °C. The reaction mixture was stirred at 0 °C for 5 min before a solution of 1-tert-butoxycarbonyl-3-pyrrolidone (9.0 g, 48 mmol) in THF (40 mL) was added via cannula. The reaction mixture was kept stirred at 0 °C for 90 min, followed by warming up to room temperature and continued stirring for 1 hour. Upon completion of the reaction, the mixture was cooled to 0 °C and quenched with saturated aqueous sodium bicarbonate (NaHCO3) and aqueous ammonium chloride (NH4Cl), followed by extraction with ether (Et2O). The organic layers were combined, dried over anhydrous magnesium sulfate (MgSO4) and concentrated under reduced pressure. The crude product was suspended with hot hexane and filtered, and the filtrate was concentrated and purified by fast column chromatography (FCC) to afford the target compound tert-butyl 3-methylene pyrrolidine-1-carboxylate (4.4 g, 50% yield).