反应详情

温度

0 °C

A solution of 3.0 g (0.017 mol) L-Leucine methyl ester hydrochloride is dissolved in 30 ml of dichloromethane. The solution is cooled to 0° C. and 4.05 ml (0.029 mol) of triethylamine is added dropwise over a ten minute period. The mixture is stirred ten minutes, filtered and concentrated at reduced pressure. The oil is dissolved in 17 ml of dichloromethane and the following is added in a single addition: 4.35 g (0.021 mol) of dicyclohexylcarbodiimide; 100 mg (0.0008 mol) of 4-dimethylaminopyridine; 2.66 g (0.017 mol) of 5-oxo-2-pyrrolidinepropanoic acid. The reaction is allowed to warm to room temperature and stirred for 20 hours. The solids are removed by filtration and are washed with 15 ml of 0° C. dichloromethane. The filtrate is concentrated at reduced pressure to an oil. The oil is chromatographed over silica gel using 93:7 dichloromethanemethanol for elution. Concentration at reduced pressure followed by heating at 0.1 mm pressure and 50 ° C. yields crystalline analytically pure (as a 0.33 hydrate) N-[1-oxo-3-(5-oxo-2-pyrrolidinyl) propyl]-L-leucine, methyl ester with a melting point of 70°-74.5° C.

1. filtrationfiltered
2. concentrationconcentrated at reduced pressure
3. dissolutionThe oil is dissolved in 17 ml of dichloromethane
4. additionthe following is added in a single addition
5. temperatureto warm to room temperature
6. stirringstirred for 20 hours
7. customThe solids are removed by filtration
8. washare washed with 15 ml of 0° C. dichloromethane
9. concentrationThe filtrate is concentrated at reduced pressure to an oil
10. customThe oil is chromatographed over silica gel using 93:7 dichloromethanemethanol for elution
11. concentrationConcentration at reduced pressure
12. temperatureby heating at 0.1 mm pressure and 50 ° C.