Mixed Anhydrides

Abstract

A solution of benzyloxycarbonyl-l-leucine (2.65 g, 10 mmol) and triethylamine (1.01 g = 1.4 ml, 10 mmol) in a mixture of toluene (12.5 ml) and chloroform (12.5 ml) is cooled to −5 °C. Isovaleryl chloride (1.205 g = 1.27 ml, 10 mmol) is added and the mixture allowed to stand at −5 °C for one and a half hours for the formation of the mixed anhydride. At that time a solution of glycine ethyl ester hydrochloride (1.4 g, 10 mmol) and triethylamine (1.4 ml, 10 mmol) in chloroform (25 ml), cooled to −5 °C, is added and the reaction mixture is set aside in a refrigerator at about 5–10 °C. Next day the solution is washed with equal volumes of water, 0.5 M KHCO₃ solution, and water again. It is dried over MgSO₄, filtered from the drying agent and concentrated in vacuo to about 15 ml. On dilution with hexane (75 ml) the product separates in crystalline form. It is collected on a filter, washed with hexane and dried in air. The crude dipeptide derivative is dissolved in boiling 95% ethanol on a steam bath and diluted with warm distilled water until turbid. On cooling, crystals separate. After several hours at room temperature the product is collected on a filter, washed with a small volume of 50% ethanol, dried in air and finally in vacuo over P₂O₅. The protected dipeptide ester weighs 2.45 g (70%) [2] and melts at 105–106 °C; [α] ²⁴_D −25.6° (c 5, ethanol).