BENZYL 2-CARBAMOYLPYRROLIDINE-1-CARBOXYLATE synthesis

Yield:93188-01-3 88%

Reaction Conditions:

Stage #1: N-carbobenzyloxyprolinewith 4-methyl-morpholine in dichloromethane at 0; for 0.166667 h;
Stage #2: with chloroformic acid ethyl ester in dichloromethane at -15; for 2 h;
Stage #3: with ammonia in dichloromethane at -20 - 0; for 1 h;

Steps:

89.2

Pyrrolidine-1,2-dicarboxylic acid 1-benzyl ester (30.0 g, 121 mmol) was dissolved in DCM (180 mL). The solution was cooled to 0° C. and N-methyl-morpholine (12.8 g, 127 mmol) was added over a period of 10 mins. The solution was then cooled to -15° C. and the ethyl chloroformate (13.7 g, 126 mmol) in DCM (30 mL) was added dropwise. The solution was then stirred for 2 hours at -25° C. Next, the solution was placed under NH₃ (g) while maintaining the temperature below -20° C. The reaction mixture was then stirred for 1 hour while allowing the temperature to return to 0° C. The solution was poured in H₂O (120 mL) and the organic layer was partitioned from the aqueous layer. The organic layer was then washed with 1N HCl (2×50 mL), 1N NaHCO₃ (2×50 mL), dried over MgSO₄ and concentrated under vacuo to afford 27.8 g (88%) of 2-carbamoyl-pyrrolidine-1-carboxylic acid benzyl ester, as a colorless oil.

References:

US2006/116515,2006,A1 Location in patent:Page/Page column 66