(2S,4S)-4-fluoropyrrolidine-2-carboxamide

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: (2S,4S)-4-Fluoropyrrolidine-2-carboxamide (119 mg, 0.9 mmol) obtained in step 1 was dissolved in 5 ml of isopropanol. Into the solution, 1.5 mL (HCl 1.5 mmol) of 1.0 M HCl in ether was added, and after the mixture was stirred for 10 minutes, all the volatiles were removed. The resulting solid was dried in vacuum at 50° C. for 2 h, giving 148 mg (yield 98%) of (2S,4S)-4-fluoropyrrolidine-2-carboxamide hydrochloride (Ga). The product was identified by comparison with an authentic sample. all the volatiles were removed The resulting solid was dried in vacuum at 50° C. for 2 h

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: (2S,4S)—N-Fmoc-4-fluoropyrrolidine-2-carboxamide (Fa) (354 mg, 1 mmol) was dissolved in 12 ml of a 1:1 mixture of diethylamine and dichloromethane at room temperature. After the mixture was stirred for 1.5 h, all the volatiles are removed. To the obtained residue was added ethyl acetate (10 ml) and water (5 mL), and the mixture was stirred and left. The aqueous layer was separated, washed with 10 ml of ethyl acetate, and evaporated to dryness by a vacuum pump. The residue was dissolved in 2 ml of isopropanol and mixed with ether. The precipitated solid was washed with ethyl acetate and dried in vacuo, giving 118 mg (yield 90%) of (2S,4S)-4-fluoropyrrolidine-2-carboxamide as crystals: 19F-NMR (D2O) δ −172.40 (m, 1 F): 1H-NMR (D2O) δ 2.0-2.5 (m, 2H), 2.95 (dd, 1H, J=38.8, 3.42 Hz), 3.20 (dd, 1H, J=21.6, 1.7 Hz), 3.0 (dd, 1H, J=10.3, 4.1 Hz), 5.16 (dt, 1H, J=53.2, 4.1 Hz): 13C-NMR (D2O) δ 37.52 (d, J=21.7 Hz), 52.68 (d, J=23.1 Hz), 58.49, 94.63 (d, J=171.2 Hz, 4-C), 177.71 (CO). all the volatiles are removed To the obtained residue was added ethyl acetate (10 ml) and water (5 mL) the mixture was stirred left The aqueous layer was separated washed with 10 ml of ethyl acetate evaporated to dryness by a vacuum pump The residue was dissolved in 2 ml of isopropanol mixed with ether The precipitated solid was washed with ethyl acetate dried in vacuo

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: (2S,4S)-4-Fluoropyrrolidine-2-carboxamide (119 mg, 0.9 mmol) obtained in step 1 was dissolved in 5 ml of isopropanol. Into the solution, 1.5 mL (HCl 1.5 mmol) of 1.0 M HCl in ether was added, and after the mixture was stirred for 10 minutes, all the volatiles were removed. The resulting solid was dried in vacuum at 50° C. for 2 h, giving 148 mg (yield 98%) of (2S,4S)-4-fluoropyrrolidine-2-carboxamide hydrochloride (Ga). The product was identified by comparison with an authentic sample. all the volatiles were removed The resulting solid was dried in vacuum at 50° C. for 2 h

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: (2S,4S)—N-Fmoc-4-fluoropyrrolidine-2-carboxamide (Fa) (354 mg, 1 mmol) was dissolved in 12 ml of a 1:1 mixture of diethylamine and dichloromethane at room temperature. After the mixture was stirred for 1.5 h, all the volatiles are removed. To the obtained residue was added ethyl acetate (10 ml) and water (5 mL), and the mixture was stirred and left. The aqueous layer was separated, washed with 10 ml of ethyl acetate, and evaporated to dryness by a vacuum pump. The residue was dissolved in 2 ml of isopropanol and mixed with ether. The precipitated solid was washed with ethyl acetate and dried in vacuo, giving 118 mg (yield 90%) of (2S,4S)-4-fluoropyrrolidine-2-carboxamide as crystals: 19F-NMR (D2O) δ −172.40 (m, 1 F): 1H-NMR (D2O) δ 2.0-2.5 (m, 2H), 2.95 (dd, 1H, J=38.8, 3.42 Hz), 3.20 (dd, 1H, J=21.6, 1.7 Hz), 3.0 (dd, 1H, J=10.3, 4.1 Hz), 5.16 (dt, 1H, J=53.2, 4.1 Hz): 13C-NMR (D2O) δ 37.52 (d, J=21.7 Hz), 52.68 (d, J=23.1 Hz), 58.49, 94.63 (d, J=171.2 Hz, 4-C), 177.71 (CO). all the volatiles are removed To the obtained residue was added ethyl acetate (10 ml) and water (5 mL) the mixture was stirred left The aqueous layer was separated washed with 10 ml of ethyl acetate evaporated to dryness by a vacuum pump The residue was dissolved in 2 ml of isopropanol mixed with ether The precipitated solid was washed with ethyl acetate dried in vacuo

反応条件: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of (2S,4S)-2-carbamoyl-4-fluoro-pyrrolidine-1-carboxylic acid tert-butyl ester (1.0 g), conc. HCl (0.6 ml) and 1-butanol (10 ml) was heated for 48 h at 50° C. The RM was evaporated and partitioned DCM and aqueous NaHCO3, the DCM layers were dried over Na2SO4 and evaporated. A solution of 7 M ammonia in methanol (10 ml) was added to the residue and the mixture was stood for 60 h at it in a sealed vessel. Evaporation and trituration with EtOH gave the title compound as a white solid. The RM was evaporated partitioned DCM and aqueous NaHCO3 the DCM layers were dried over Na2SO4 evaporated A solution of 7 M ammonia in methanol (10 ml) was added to the residue Evaporation and trituration with EtOH

反応条件: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of (2S,4S)-2-carbamoyl-4-fluoro-pyrrolidine-1-carboxylic acid tert-butyl ester (1.0 g), conc. Hydrochoric acid (0.6 ml) and 1-butanol (10 ml) is heated for 48 hours at 50° C. The reaction mixture is evaporated and partitioned dichloromethane and aqueous sodium bicarbonate, the dichloromethane layers are dried over sodium sulphate and evaporated. A solution of 7M ammonia in methanol (10 ml) is added to the residue and the mixture is stood for 60 hours at room temperature in a sealed vessel. Evaporation and trituration with ethanol gives the title compound as a white solid. The reaction mixture is evaporated partitioned dichloromethane and aqueous sodium bicarbonate the dichloromethane layers are dried over sodium sulphate evaporated A solution of 7M ammonia in methanol (10 ml) is added to the residue Evaporation and trituration with ethanol

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: (2S,4S)-4-Fluoropyrrolidine-2-carboxamide (119 mg, 0.9 mmol) obtained in step 1 was dissolved in 5 ml of isopropanol. Into the solution, 1.5 mL (HCl 1.5 mmol) of 1.0 M HCl in ether was added, and after the mixture was stirred for 10 minutes, all the volatiles were removed. The resulting solid was dried in vacuum at 50° C. for 2 h, giving 148 mg (yield 98%) of (2S,4S)-4-fluoropyrrolidine-2-carboxamide hydrochloride (Ga). The product was identified by comparison with an authentic sample. all the volatiles were removed The resulting solid was dried in vacuum at 50° C. for 2 h

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: (2S,4S)—N-Fmoc-4-fluoropyrrolidine-2-carboxamide (Fa) (354 mg, 1 mmol) was dissolved in 12 ml of a 1:1 mixture of diethylamine and dichloromethane at room temperature. After the mixture was stirred for 1.5 h, all the volatiles are removed. To the obtained residue was added ethyl acetate (10 ml) and water (5 mL), and the mixture was stirred and left. The aqueous layer was separated, washed with 10 ml of ethyl acetate, and evaporated to dryness by a vacuum pump. The residue was dissolved in 2 ml of isopropanol and mixed with ether. The precipitated solid was washed with ethyl acetate and dried in vacuo, giving 118 mg (yield 90%) of (2S,4S)-4-fluoropyrrolidine-2-carboxamide as crystals: 19F-NMR (D2O) δ −172.40 (m, 1 F): 1H-NMR (D2O) δ 2.0-2.5 (m, 2H), 2.95 (dd, 1H, J=38.8, 3.42 Hz), 3.20 (dd, 1H, J=21.6, 1.7 Hz), 3.0 (dd, 1H, J=10.3, 4.1 Hz), 5.16 (dt, 1H, J=53.2, 4.1 Hz): 13C-NMR (D2O) δ 37.52 (d, J=21.7 Hz), 52.68 (d, J=23.1 Hz), 58.49, 94.63 (d, J=171.2 Hz, 4-C), 177.71 (CO). all the volatiles are removed To the obtained residue was added ethyl acetate (10 ml) and water (5 mL) the mixture was stirred left The aqueous layer was separated washed with 10 ml of ethyl acetate evaporated to dryness by a vacuum pump The residue was dissolved in 2 ml of isopropanol mixed with ether The precipitated solid was washed with ethyl acetate dried in vacuo