tert-butyl (2S)-2-[(2-methoxy-2-oxoethyl)carbamoyl]pyrrolidine-1-carboxylate

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of Boc-Pro-OH (73.2 g, 340 mmol) and triethylamine (47.6 ml, 340 mmol) in tetrahydrofurane (300 ml), cooled to -10°, was added isobutyl chloroformate (44.5 ml, 340 mmol). After 15 min., a solution of H-Gly-OMe.HCl (42.7 g, 340 mmol) and triethylamine (47.6 ml, 340 mmol) in chloroform (300 ml) was added to the stirring solution. The mixture was stirred at 0° for 1 h and at room temperature for 24 h. The organic solvent was removed under reduced pressure and the residue, dissolved in ethyl acetate, was washed with 10% citric acid solution, 4% sodium bicarbonate solution, water and dried over anhydrous sodium sulfate. The solution was evaporated and the oily residue was crystallized on addition of petroleum ether; yield 71.8 g (84%), m.p. 70-72° C., Rf1 0.70. Calcd. for C13H22N2O5 :C, 54.53; H, 7.75; N, 9.78%. Found: C, 55.03; H, 7.58; N, 9.34%. The organic solvent was removed under reduced pressure the residue, dissolved in ethyl acetate was washed with 10% citric acid solution, 4% sodium bicarbonate solution, water dried over anhydrous sodium sulfate The solution was evaporated the oily residue was crystallized on addition of petroleum ether

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of Boc-Pro-OH (73.2 g, 340 mmol) and triethylamine (47.6 ml, 340 mmol) in tetrahydrofurane (300 ml), cooled to -10°, was added isobutyl chloroformate (44.5 ml, 340 mmol). After 15 min., a solution of H-Gly-OMe.HCl (42.7 g, 340 mmol) and triethylamine (47.6 ml, 340 mmol) in chloroform (300 ml) was added to the stirring solution. The mixture was stirred at 0° for 1 h and at room temperature for 24 h. The organic solvent was removed under reduced pressure and the residue, dissolved in ethyl acetate, was washed with 10% citric acid solution, 4% sodium bicarbonate solution, water and dried over anhydrous sodium sulfate. The solution was evaporated and the oily residue was crystallized on addition of petroleum ether; yield 71.8 g (84%), m.p. 70°-72° C., Rf1 0.70. The organic solvent was removed under reduced pressure the residue, dissolved in ethyl acetate was washed with 10% citric acid solution, 4% sodium bicarbonate solution, water dried over anhydrous sodium sulfate The solution was evaporated the oily residue was crystallized on addition of petroleum ether