反应详情

1-ethyl-5-oxoproline (0.100 g, 0.64 mmol) was dissolved in a mixture of dichloromethane (3 ml) and dimethylformamide (0.5 ml) and to this was added N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (0.147 g, 0.77 mmol), 1-hydroxybenzotriazole (0.104 g, 0.77 mmol), and N-ethyl morpholine (0.244 ml, 1.92 mmol). The mixture was stirred for 10 minutes and then 2-chloro-4-fluorobenzylamine was added to the mixture and stirring continued overnight (˜16 hrs) at room temperature. The mixture was then treated with saturated aqueous sodium hydrogen carbonate (˜2 ml) and stirred vigorously for ˜10 minutes. The aqueous layer was removed using a phase separator and extracted with more dichloromethane (2×1 ml). The combined organic layers were concentrated to give a yellow oil and this was subsequently purified by mass-directed automated HPLC to give N-[(2-chloro-4-fluorophenyl)methyl]-1-ethyl-5-oxo-D-prolinamide (0.065 g) as a white solid. LC/MS [M+H]+=299, retention time=2.16 minutes.

1. stirringstirring continued overnight (˜16 hrs) at room temperature
2. stirringstirred vigorously for ˜10 minutes
3. customThe aqueous layer was removed
4. extractionextracted with more dichloromethane (2×1 ml)
5. concentrationThe combined organic layers were concentrated
6. customto give a yellow oil
7. customthis was subsequently purified