Imidazole → HCID 68036711, compound

Temperature

-35 °C

In a dry three-necked flask, 286 mL of pyridine, (S)-[2-(2-carbamoyl-pyrrolidin-1-yl)-2-oxo-ethyl]-carbamic acid tert-butyl ester 1b (13.5 g, 49.8 mmol) and imidazole (7.11 g, 104.6 mmol) were added successively under nitrogen atmosphere. Then the reaction system was cooled to −35° C. followed by dropwise addition of phosphorus oxychloride (19 mL, 204.2 mmol) with stirring. The reaction mixture was stirred for 1 hour at the same temperature. After warmed up to room temperature, the reaction mixture was stirred for another 30 minutes. The mixture was evaporated to remove pyridine and the resulting mixture was diluted with ethyl acetate followed by addition of water. The mixture 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 resulting residue was purified by silica gel column chromatography to obtain the title compound (S)-[2-(2-cyano-pyrrolidin-1-yl)-2-oxo-ethyl]-carbamic acid tert-butyl ester 1c (10.7 g, yield 84.9%) as a white powder.

1. stirringThe reaction mixture was stirred for 1 hour at the same temperature
2. temperatureAfter warmed up to room temperature
3. stirringthe reaction mixture was stirred for another 30 minutes
4. customThe mixture was evaporated
5. customto remove pyridine
6. additionthe resulting mixture was diluted with ethyl acetate
7. additionfollowed by addition of water
8. extractionThe mixture was extracted with ethyl acetate (200 mL×3)
9. washThe combined organic extracts were washed with 50 mL of saturated brine
10. dry with materialdried over anhydrous sodium sulfate
11. filtrationfiltered
12. concentrationconcentrated under reduced pressure
13. customThe resulting residue was purified by silica gel column chromatography

ORD record

ord-327faaa756d2474f9f5cf1d1e622bc78

Source dataset

uspto-grants-2013_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08415349B2