Potassium Carbonate → (2S,4S)-4-fluoro-1-(2-((2-methyl-4-oxo-4-pyrrolidin-1-ylbutan-2-yl)amino)acetyl)pyrrolidine-2-carbonitrile

To a stirred solution of 3-amino-3-methyl-1-pyrrolidin-1-yl-butan-1-one trifluoroacetic acid (0.28 g, 1 mmol) in anhydrous THF (5 mL) was added potassium carbonate (0.55 g, 4 mmol). After stirred at room temperature for 1 h, the mixture was filtered through a Celite pad, and rinsed with ethyl acetate (5 mL). To the above filtrate was added (2S,4S)-1-(2-bromoacetyl)-4-fluoropyrrolidine-2-carbonitrile (0.12 g, 0.5 mmol) and the reaction mixture was stirred at room temperature under nitrogen for 12 h. Most of solvent was removed under reduced pressure and the residue was partitioned between CH2Cl2 (20 mL) and H2O (5 mL). The aqueous layer was further extracted with CH2Cl2 (10 mL). The combined organic layers were dried over magnesium sulfate, filtered, and concentrated under reduced pressure to yield a crude viscous oil. The crude oil was purified by chromatography (silica gel, 4 to 10% CH3OH/CH2Cl2 gradient) to give compound 1 (0.12 g, 74% overall yield) as a white solid.

1. filtrationthe mixture was filtered through a Celite pad
2. washrinsed with ethyl acetate (5 mL)
3. stirringthe reaction mixture was stirred at room temperature under nitrogen for 12 h
4. customMost of solvent was removed under reduced pressure
5. customthe residue was partitioned between CH2Cl2 (20 mL) and H2O (5 mL)
6. extractionThe aqueous layer was further extracted with CH2Cl2 (10 mL)
7. dry with materialThe combined organic layers were dried over magnesium sulfate
8. filtrationfiltered
9. concentrationconcentrated under reduced pressure
10. customto yield a crude viscous oil
11. customThe crude oil was purified by chromatography (silica gel, 4 to 10% CH3OH/CH2Cl2 gradient)

ORD record

ord-75b4ec1324a3404eb072a3ae293c6661

Source dataset

uspto-grants-2011_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08022096B2