(S)-2-Benzyl 1-tert-butyl pyrrolidine-1,2-dicarboxylate

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

Procedure: The solution of 33 mg (0.10 mmol) of Cs2CO3 in 0.1 ml of distilled water was added to the solution of 43 mg (0.20 mmol) Boc-Pro-OH in 2 ml of anhydrous ethanol. The mixture was stirred at room temperature for 40 min and then evaporated to dryness. The residue was dried over anhydrous CaCl2 to provide a colorless powder which was dissolved in 1 ml of DMF. To the DMF solution 34 mg (0.2 mmol) of benzyl bromide was added slowly. The mixture was stirred at 50° C. for 16 hr and the formed precipitates of CsBr were filteled. The filtrate was evaporated to dry. The residue was dissolved in 20 ml of ethyl acetate and the solution was washed with saturated solution of NaHCO3, NaCl and 5% solution of KHSO4 successively. The organic phase was separated and dried over anhydrous NaSO4. After filtration the filtrate was evaporated at 37° C. to provide 54 mg (88%) of the title compound as a colorless syrupy. evaporated to dryness The residue was dried over anhydrous CaCl2 to provide a colorless powder which The mixture was stirred at 50° C. for 16 hr the formed precipitates of CsBr The filtrate was evaporated to dry The residue was dissolved in 20 ml of ethyl acetate the solution was washed with saturated solution of NaHCO3, NaCl and 5% solution of KHSO4 successively The organic phase was separated dried over anhydrous NaSO4 After filtration the filtrate was evaporated at 37° C.

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

Procedure: Boc-Pro-OH (50.0 g, 0.23 mol) was dissolved in dichloromethane (500 mL), and EDCI (89.1 g, 0.46 mol), DMAP (5.7 g, 0.05 mol), DIPEA (162 mL, 0.93 mol) and benzyl alcohol (48 mL, 0.46 mol) were added dropwise. The mixture was stirred at room temperature for 12 hours. The mixture was washed several times with an aqueous solution of 5% citric acid. The organic layer was dried over sodium sulfate, and filtered and distilled under reduced pressure to obtain the title compound as yellow oil (70.0 g, 99%). The mixture was washed several times with an aqueous solution of 5% citric acid The organic layer was dried over sodium sulfate filtered distilled under reduced pressure

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

Procedure: While cooling on ice, Boc-L-Pro-OH (1.08 g, 5.0 mmol) and benzyl bromide (0.893 ml, 75 mmol) were reacted in DMF (10 ml) in the presence of triethylamine (10.5 ml, 75 mmol) to obtain Boc-L-Pro-OBzl as an oily product. This product was reacted under ice-cooling with 2 N HCl/dioxane (5 eq.) for three hours to obtain H-L-Pro-OBzl-HCl.

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

Procedure: The solution of 33 mg (0.10 mmol) of Cs2CO3 in 0.1 ml of distilled water was added to the solution of 43 mg (0.20 mmol) Boc-Pro-OH in 2 ml of anhydrous ethanol. The mixture was stirred at room temperature for 40 min and then evaporated to dryness. The residue was dried over anhydrous CaCl2 to provide a colorless powder which was dissolved in 1 ml of DMF. To the DMF solution 34 mg (0.2 mmol) of benzyl bromide was added slowly. The mixture was stirred at 50° C. for 16 hr and the formed precipitates of CsBr were filteled. The filtrate was evaporated to dry. The residue was dissolved in 20 ml of ethyl acetate and the solution was washed with saturated solution of NaHCO3, NaCl and 5% solution of KHSO4 successively. The organic phase was separated and dried over anhydrous NaSO4. After filtration the filtrate was evaporated at 37° C. to provide 54 mg (88%) of the title compound as a colorless syrupy. evaporated to dryness The residue was dried over anhydrous CaCl2 to provide a colorless powder which The mixture was stirred at 50° C. for 16 hr the formed precipitates of CsBr The filtrate was evaporated to dry The residue was dissolved in 20 ml of ethyl acetate the solution was washed with saturated solution of NaHCO3, NaCl and 5% solution of KHSO4 successively The organic phase was separated dried over anhydrous NaSO4 After filtration the filtrate was evaporated at 37° C.