Triethylamine → [2-(2-Carbamoyl-pyrrolidin-1-yl)-2-oxo-ethyl]-carbamic acid tert-butyl ester

N-tert-butyloxycarbonyl glycine 1a (5 g, 28.56 mmol) and L-prolinamide (3.25 g, 28.50 mmol) were dissolved in 75 mL of N,N-dimethylformamide, the resulting solution was cooled down to 0° C. (centigrade), and 1-hydroxybenzotriazole (11.8 g, 87.3 mmol), N-ethyl-N′-(dimethylaminopropyl)-carbodiimide (11.3 g, 59 mmol) and triethylamine (12.1 mL, 87.3 mmol) were then added with stirring. Upon completion of the addition, the reaction mixture was allowed to increase to room temperature, and stirred overnight. After thin lay chromatography showed the starting material disappeared, N,N-dimethylformamide was evaporated below 50° C., and the reaction solution was extracted with ethyl acetate (200 mL×3). The combined organic extracts were washed with 50 mL of saturated brine, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by recrystallization with ethyl acetate to obtain the title compound [2-(2-carbamoyl-pyrrolidin-1-yl)-2-oxo-ethyl]-carbamic acid tert-butyl ester 1b (7.42 g, yield 95.8%) as a white powder.

1. additionwere then added
2. additionUpon completion of the addition
3. stirringstirred overnight
4. customN,N-dimethylformamide was evaporated below 50° C.
5. extractionthe reaction solution was extracted with ethyl acetate (200 mL×3)
6. washThe combined organic extracts were washed with 50 mL of saturated brine
7. dry with materialdried over anhydrous sodium sulfate
8. filtrationfiltered
9. concentrationconcentrated under reduced pressure
10. customThe residue was purified by recrystallization with ethyl acetate

ORD record

ord-045c53ae26ef4ce183903edc9867ab53

Source dataset

uspto-grants-2012_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08178575B2