tert-butyl pyrrolidine-3-carboxylate

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

Procedure: To a solution of 1-naphthalenesulfonyl chloride (1.0 g, 5.4 mmol) in 50 ml of CH2Cl2 with 2 ml of trimethylamine was added 3-t-butoxycarbonylpyrrolidine (1.5 g, 6.5 mmol) in a portion and the resulting solution was stirred at reflux for 48 h. Reaction mixture was concentrated in vacuo, yielding oily mixture which was partioned between 100 ml of EtOAc and NaHCO3 sat'd aqueous solution. Organic layer was separated, dried over Na2SO4 and concentrated in vacuo to provide an oil, which was redissolved in 20 ml of CH2Cl2. Toward this solution was added 1 ml of trifluoroacetic acid and the resulting solution was stirred for 2 h at 25° C. Reaction mixture was concentrated in vacuo, providing a brown oil, which was dissolved in EtOAc and washed with aqueous NaOH. organic layer was concentrated in vacuo to yield an oil which was subjected to column chromatography (30% MeOH/CHCl3) to provide 0.17 g (23%) of the desired product. at reflux for 48 h Reaction mixture was concentrated in vacuo yielding oily mixture which Organic layer was separated dried over Na2SO4 concentrated in vacuo to provide an oil, which the resulting solution was stirred for 2 h at 25° C Reaction mixture was concentrated in vacuo providing a brown oil, which washed with aqueous NaOH organic layer was concentrated in vacuo to yield an oil which

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

Procedure: Stir a solution of diisopropylethylamine (9.5 mL, 54.3 mmol), 6-chloronicotinonitrile (5 g, 36.2 mmol) and 3-tert-butyloxycarbonylpyrrolidine (10 g, 54.3 mmol) in DMF (10 mL). After 3 days, dilute with dichloromethane and an aqueous saturated solution of sodium bicarbonate and separate the layers. Extract the aqueous layer once with dichloromethane, dry (sodium sulfate), filter and concentrate. Filter through a plug of silica gel, wash with dichloromethane and concentrate to give [1-(5-cyanopyridin-2-yl)-pyrrolidin-3-yl]-carbamic acid tert-butyl ester as a white solid (8.13 g, 78%). 1H NMR (400 MHz, CDCl3) δ 8.38 (dd, 1H, J=2.4 Hz, 1.0 Hz), 7.58-7.55 (m, 1H), 6.33 (dd, 1H, J=9.8 Hz, 1.0 Hz), 4.85-4.7 (m, 1H), 4.40-4.25 (m, 1H), 3.85-3.30 (m, 4H), 2.35-2.25 (m, 1H), 2.08-1.90 (m, 1H), 1.43 (s, 9H); MS (ES): m/z=289 [M+H]+. an aqueous saturated solution of sodium bicarbonate and separate the layers Extract the aqueous layer once with dichloromethane dry (sodium sulfate) filter concentrate Filter through a plug of silica gel wash with dichloromethane concentrate

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

Procedure: Stir a solution of diisopropylethylamine (9.5 mL, 54.3 mmol), 6-chloronicotinonitrile (5 g, 36.2 mmol) and 3-tert-butyloxycarbonylpyrrolidine (10 g, 54.3 mmol) in DMF (10 mL). After 3 days, dilute with dichloromethane and an aqueous saturated solution of sodium bicarbonate and separate the layers. Extract the aqueous layer once with dichloromethane, dry (sodium sulfate), filter and concentrate. Filter through a plug of silica gel, wash with dichloromethane and concentrate to give [1-(5-cyanopyridin-2-yl)-pyrrolidin-3-yl]-carbamic acid tert-butyl ester as a white solid (8.13 g, 78%). 1H NMR (400 MHz, CDCl3) δ 8.38 (dd, 1H, J=2.4 Hz, 1.0 Hz), 7.58-7.55 (m, 1H), 6.33 (dd, 1H, J=9.8 Hz, 1.0 Hz), 4.85-4.7 (m, 1H), 4.40-4.25 (m, 1H), 3.85-3.30 (m, 4H), 2.35-2.25 (m, 1H), 2.08-1.90 (m, 1H), 1.43 (s, 9H); MS (ES): m/z=289 [M+H]+. an aqueous saturated solution of sodium bicarbonate and separate the layers Extract the aqueous layer once with dichloromethane dry (sodium sulfate) filter concentrate Filter through a plug of silica gel wash with dichloromethane concentrate

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

Procedure: To a solution of 1-naphthalenesulfonyl chloride (1.0 g, 5.4 mmol) in 50 ml of CH2Cl2 with 2 ml of trimethylamine was added 3-t-butoxycarbonylpyrrolidine (1.5 g, 6.5 mmol) in a portion and the resulting solution was stirred at reflux for 48 h. Reaction mixture was concentrated in vacuo, yielding oily mixture which was partioned between 100 ml of EtOAc and NaHCO3 sat'd aqueous solution. Organic layer was separated, dried over Na2SO4 and concentrated in vacuo to provide an oil, which was redissolved in 20 ml of CH2Cl2. Toward this solution was added 1 ml of trifluoroacetic acid and the resulting solution was stirred for 2 h at 25° C. Reaction mixture was concentrated in vacuo, providing a brown oil, which was dissolved in EtOAc and washed with aqueous NaOH. organic layer was concentrated in vacuo to yield an oil which was subjected to column chromatography (30% MeOH/CHCl3) to provide 0.17 g (23%) of the desired product. at reflux for 48 h Reaction mixture was concentrated in vacuo yielding oily mixture which Organic layer was separated dried over Na2SO4 concentrated in vacuo to provide an oil, which the resulting solution was stirred for 2 h at 25° C Reaction mixture was concentrated in vacuo providing a brown oil, which washed with aqueous NaOH organic layer was concentrated in vacuo to yield an oil which

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

Procedure: To a solution of 1-naphthalenesulfonyl chloride (1.0 g, 5.4 mmol) in 50 ml of CH2Cl2 with 2 ml of trimethylamine was added 3-t-butoxycarbonylpyrrolidine (1.5 g, 6.5 mmol) in a portion and the resulting solution was stirred at reflux for 48 h. Reaction mixture was concentrated in vacuo, yielding oily mixture which was partioned between 100 ml of EtOAc and NaHCO3 sat'd aqueous solution. Organic layer was separated, dried over Na2SO4 and concentrated in vacuo to provide an oil, which was redissolved in 20 ml of CH2Cl2. Toward this solution was added 1 ml of trifluoroacetic acid and the resulting solution was stirred for 2 h at 25° C. Reaction mixture was concentrated in vacuo, providing a brown oil, which was dissolved in EtOAc and washed with aqueous NaOH. organic layer was concentrated in vacuo to yield an oil which was subjected to column chromatography (30% MeOH/CHCl3) to provide 0.17 g (23%) of the desired product. at reflux for 48 h Reaction mixture was concentrated in vacuo yielding oily mixture which Organic layer was separated dried over Na2SO4 concentrated in vacuo to provide an oil, which the resulting solution was stirred for 2 h at 25° C Reaction mixture was concentrated in vacuo providing a brown oil, which washed with aqueous NaOH organic layer was concentrated in vacuo to yield an oil which

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

Procedure: Stir a solution of diisopropylethylamine (9.5 mL, 54.3 mmol), 6-chloronicotinonitrile (5 g, 36.2 mmol) and 3-tert-butyloxycarbonylpyrrolidine (10 g, 54.3 mmol) in DMF (10 mL). After 3 days, dilute with dichloromethane and an aqueous saturated solution of sodium bicarbonate and separate the layers. Extract the aqueous layer once with dichloromethane, dry (sodium sulfate), filter and concentrate. Filter through a plug of silica gel, wash with dichloromethane and concentrate to give [1-(5-cyanopyridin-2-yl)-pyrrolidin-3-yl]-carbamic acid tert-butyl ester as a white solid (8.13 g, 78%). 1H NMR (400 MHz, CDCl3) δ 8.38 (dd, 1H, J=2.4 Hz, 1.0 Hz), 7.58-7.55 (m, 1H), 6.33 (dd, 1H, J=9.8 Hz, 1.0 Hz), 4.85-4.7 (m, 1H), 4.40-4.25 (m, 1H), 3.85-3.30 (m, 4H), 2.35-2.25 (m, 1H), 2.08-1.90 (m, 1H), 1.43 (s, 9H); MS (ES): m/z=289 [M+H]+. an aqueous saturated solution of sodium bicarbonate and separate the layers Extract the aqueous layer once with dichloromethane dry (sodium sulfate) filter concentrate Filter through a plug of silica gel wash with dichloromethane concentrate

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

Procedure: To a solution of l-naphthalenesulfonyl chloride (1,0 g, 5.4 mmol) in 50 ml of CH2Cl2 with 2 ml of trimethylamine was added 3-t-butoxycarbonylpyrrolidine (1.5 g, 6.5 mmol) in a portion and the resulting solution was stirred at reflux for 48 h. Reaction mixture was concentrated in vacuo, yielding oily mixture which was partioned between 100 ml of EtOAc and NaHCO3 sat'd aqueous solution. Organic layer was separated, dried over Na2SO4 and concentrated in vacuo to provide an oil, which was redissolved in 20 ml of CH2Cl2. Toward this solution was added 1 ml of trifluoroacetic acid and the resulting solution was stirred for 2 h at 25° C. Reaction mixture was concentrated in vacuo, providing a brown oil, which was dissolved in EtOAc and washed with aqueous NaOH, Organic layer was concentrated in vacuo to yield an oil which was subjected to column chromatography (30% MeOH/CHCl3) to provide 0.17 g (23%) of the desired product. at reflux for 48 h Reaction mixture was concentrated in vacuo yielding oily mixture which Organic layer was separated dried over Na2SO4 concentrated in vacuo to provide an oil, which the resulting solution was stirred for 2 h at 25° C Reaction mixture was concentrated in vacuo providing a brown oil, which washed with aqueous NaOH, Organic layer was concentrated in vacuo to yield an oil which

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

Procedure: To a solution of 1-naphthalenesulfonyl chloride (1.0 g, 5.4 mmol) in 50 ml of CH2Cl2 with 2 ml of trimethylamine was added 3-t-butoxycarbonylpyrrolidine (1.5 g, 6.5 mmol) in a portion and the resulting solution was stirred at reflux for 48 h. Reaction mixture was concentrated in vacuo, yielding oily mixture which was partioned between 100 ml of EtOAc and NaHCO3 sat'd aqueous solution. Organic layer was separated, dried over Na2SO4 and concentrated in vacuo to provide an oil, which was redissolved in 20 ml of CH2Cl2. Toward this solution was added 1 ml of trifluoroacetic acid and the resulting solution was stirred for 2 h at 25° C. Reaction mixture was concentrated in vacuo, providing a brown oil, which was dissolved in EtOAc and washed with aqueous NaOH. organic layer was concentrated in vacuo to yield an oil which was subjected to column chromatography (30% MeOH/CHCl3) to provide 0.17 g (23%) of the desired product. at reflux for 48 h Reaction mixture was concentrated in vacuo yielding oily mixture which Organic layer was separated dried over Na2SO4 concentrated in vacuo to provide an oil, which the resulting solution was stirred for 2 h at 25° C Reaction mixture was concentrated in vacuo providing a brown oil, which washed with aqueous NaOH organic layer was concentrated in vacuo to yield an oil which

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

Procedure: Stir a solution of diisopropylethylamine (9.5 mL, 54.3 mmol), 6-chloronicotinonitrile (5 g, 36.2 mmol) and 3-tert-butyloxycarbonylpyrrolidine (10 g, 54.3 mmol) in DMF (10 mL). After 3 days, dilute with dichloromethane and an aqueous saturated solution of sodium bicarbonate and separate the layers. Extract the aqueous layer once with dichloromethane, dry (sodium sulfate), filter and concentrate. Filter through a plug of silica gel, wash with dichloromethane and concentrate to give [1-(5-cyanopyridin-2-yl)-pyrrolidin-3-yl]-carbamic acid tert-butyl ester as a white solid (8.13 g, 78%). 1H NMR (400 MHz, CDCl3) δ 8.38 (dd, 1H, J=2.4 Hz, 1.0 Hz), 7.58-7.55 (m, 1H), 6.33 (dd, 1H, J=9.8 Hz, 1.0 Hz), 4.85-4.7 (m, 1H), 4.40-4.25 (m, 1H), 3.85-3.30 (m, 4H), 2.35-2.25 (m, 1H), 2.08-1.90 (m, 1H), 1.43 (s, 9H); MS (ES): m/z=289 [M+H]+. an aqueous saturated solution of sodium bicarbonate and separate the layers Extract the aqueous layer once with dichloromethane dry (sodium sulfate) filter concentrate Filter through a plug of silica gel wash with dichloromethane concentrate