(S)-N-alpha-t-Butyloxycarbonyl-pyroglutamic acid t-butyl ester

24424-99-5

35418-16-7

91229-91-3

General procedure for the synthesis of tert-butyl (S)-N-Boc-pyrrolidone-5-carboxylate from di-tert-butyl dicarbonate and tert-butyl (S)-5-oxopyrrolidine-2-carboxylate: to a 1 L round bottom flask was added 40 g (216 mmol) of tert-butyl (S)-5-oxopyrrolidine-2-carboxylate followed by 350 mL of acetonitrile (MeCN). The reaction mixture was cooled to 50 °C, followed by the addition of 4-dimethylaminopyridine (DMAP, 0.5 g, 4.32 mmol) and di-tert-butyl dicarbonate (Boc2O, 47.1 g, 216 mmol). The reaction was allowed to warm up slowly to room temperature over 30 minutes. After 1.5 hours of reaction, thin layer chromatography (TLC) analysis showed that the reaction was complete. Water (300 mL) and isopropyl acetate (IPAc, 400 mL) were added to the reaction mixture, and the mixture was transferred to a 2L dispensing funnel. The aqueous layer was separated and the organic layer was dried with anhydrous magnesium sulfate (MgSO4), filtered and concentrated to obtain an oil. The oil was dissolved in a minimal amount of ethyl acetate (EtOAc) and chromatographically separated on a 600g silica gel column with an elution gradient of 100% hexane to 1:1 hexane/ethyl acetate. The target fraction was collected and concentrated to afford 60 g (210 mmol, 97% yield) of di-tert-butyl (S)-5-oxopyrrolidine-1,2-dicarboxylate.1H NMR (500 MHz, CDCl3): δ 4.5 (dd, J=2.5,6.85 Hz, 1H), 2.4-2.7 (m, 2H), 2.3 (m, 1H), 2.0 (m. 1H), 1.57 (s, 9H), 1.50 (s, 9H).