(2S,4S)-1-(2-((1,1-Dimethyl-3-oxo-3-(1-pyrrolidinyl)propyl)amino)acetyl)-4-fluoro-2-pyrrolidinecarbonitrile

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 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. the mixture was filtered through a Celite pad rinsed with ethyl acetate (5 mL) the reaction mixture was stirred at room temperature under nitrogen for 12 h Most of solvent was removed under reduced pressure 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 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)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 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. the mixture was filtered through a Celite pad rinsed with ethyl acetate (5 mL) the reaction mixture was stirred at room temperature under nitrogen for 12 h Most of solvent was removed under reduced pressure 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 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)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 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. the mixture was filtered through a Celite pad rinsed with ethyl acetate (5 mL) the reaction mixture was stirred at room temperature under nitrogen for 12 h Most of solvent was removed under reduced pressure 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 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)