pyrrolidine-2-carbonitrile;hydrochloride

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

Procedure: t-Butoxycarbonyl-L-glutamic acid 5-benzyl ester (A) (0.65 g, 2 mmol) and N-hydroxysuccinimide (HOSu, 0.23 g, 2 mmol) were dissolved in 6 ml of CH2Cl2/4-dioxane (2/1). The solution was cooled in an ice-water bath and dicyclohexylcarbodimide (DCC, 0.45 g, 2.2 mmol) was added with stirring. The reaction mixture was stirred at room temperature for 1 hour and then pyrrolidine-2-carbonitrile hydrochloride (B) (0.27 g, 2 mmol) and triethylamine (Et3N, 0.22 g, 2.2 mmol) were added. After 4 hours at room temperature, DCC was removed by filtration and washed by CH2Cl2. The filtrate and washings were combined and washed with 10% aqueous citric acid and then saturated aqueous NaHCO3, dried over MgSO4, and concentrated in vacuo. Further purification by flash column chromatography (eluted with 5/4/1 hexane/CH2Cl2/EA) afforded compound (C) (80%) as a foam. The solution was cooled in an ice-water bath The reaction mixture was stirred at room temperature for 1 hour DCC was removed by filtration washed by CH2Cl2 washed with 10% aqueous citric acid saturated aqueous NaHCO3, dried over MgSO4 concentrated in vacuo Further purification by flash column chromatography (eluted with 5/4/1 hexane/CH2Cl2/EA)

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

Procedure: t-Butoxycarbonyl-L-glutamic acid 5-benzyl ester (A) (0.65 g, 2 mmol) and N-hydroxysuccinimide (HOSu, 0.23 g, 2 mmol) were dissolved in 6 ml of CH2Cl2/4-dioxane (2/1). The solution was cooled in an ice-water bath and dicyclohexylcarbodimide (DCC, 0.45 g, 2.2 mmol) was added with stirring. The reaction mixture was stirred at room temperature for 1 hour and then pyrrolidine-2-carbonitrile hydrochloride (B) (0.27 g, 2 mmol) and triethylamine (Et3N, 0.22 g, 2.2 mmol) were added. After 4 hours at room temperature, DCC was removed by filtration and washed by CH2Cl2. The filtrate and washings were combined and washed with 10% aqueous citric acid and then saturated aqueous NaHCO3, dried over MgSO4, and concentrated in vacuo. Further purification by flash column chromatography (eluted with 5/4/1 hexane/CH2Cl2/EA) afforded compound (C) (80%) as a foam. The solution was cooled in an ice-water bath The reaction mixture was stirred at room temperature for 1 hour DCC was removed by filtration washed by CH2Cl2 washed with 10% aqueous citric acid saturated aqueous NaHCO3, dried over MgSO4 concentrated in vacuo Further purification by flash column chromatography (eluted with 5/4/1 hexane/CH2Cl2/EA)