methyl 1-methyl-2-oxopyrrolidine-3-carboxylate

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

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

実験手順: To a solution of diisopropylamine (11.3 g, 0.11 mol) in THF (150 ml), at -78° was added n-butyl lithium (60 mls of a 1.6M solution in hexane). The solution was stirred for 0.5 hours before adding N-methyl-2-pyrrolidone (10.1 g; 0.1 mol) in THF (50 ml) over a period of 5 minutes. After 0.75 hours. a solution of dimethylcarbonate (10.8 g: 0.12 mols) in THF (30 ml) was added and the reaction mixture allowed to warm to room temperature overnight. The reaction mixture was poured into water (50 ml) and extracted with dichloromethane (3×150 ml). The combined extracts were dried (Na2SO4) and evaporated in vacuo. The crude product was chromatographed on silica gel using ethyl acetate/methanol (2:1) as eluant to afford the title product as a clear liquid (4 g). δ(CDCl3) 1.90-2.70 (2H, m, CH2); 2.80 (3H, s, CH3) 3.20-3.60 (3H, m, CH and CH2); 3.70 (3H, s, CO2CH3). After 0.75 hours extracted with dichloromethane (3×150 ml) The combined extracts were dried (Na2SO4) evaporated in vacuo The crude product was chromatographed on silica gel

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

実験手順: To a solution of diisopropylamine (11.3 g, 0.11 mol) in THF (150 ml), at -78° was added n-butyl lithium (60 mls of a 1.6M solution in hexane). The solution was stirred for 0.5 hours before adding N-methyl-2-pyrrolidone (10.1 g; 0.1 mol) in THF (50 ml) over a period of 5 minutes. After 0.75 hours. a solution of dimethylcarbonate (10.8 g: 0.12 mols) in THF (30 ml) was added and the reaction mixture allowed to warm to room temperature overnight. The reaction mixture was poured into water (50 ml) and extracted with dichloromethane (3×150 ml). The combined extracts were dried (Na2SO4) and evaporated in vacuo. The crude product was chromatographed on silica gel using ethyl acetate/methanol (2:1) as eluant to afford the title product as a clear liquid (4 g). δ(CDCl3) 1.90-2.70 (2H, m, CH2); 2.80 (3H, s, CH3) 3.20-3.60 (3H, m, CH and CH2); 3.70 (3H, s, CO2CH3). After 0.75 hours extracted with dichloromethane (3×150 ml) The combined extracts were dried (Na2SO4) evaporated in vacuo The crude product was chromatographed on silica gel

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

実験手順: To a solution of diisopropylamine (11.3 g, 0.11 mol) in THF (150 ml), at -78° was added n-butyl lithium (60 mls of a 1.6M solution in hexane). The solution was stirred for 0.5 hours before adding N-methyl-2-pyrrolidone (10.1 g; 0.1 mol) in THF (50 ml) over a period of 5 minutes. After 0.75 hours. a solution of dimethylcarbonate (10.8 g: 0.12 mols) in THF (30 ml) was added and the reaction mixture allowed to warm to room temperature overnight. The reaction mixture was poured into water (50 ml) and extracted with dichloromethane (3×150 ml). The combined extracts were dried (Na2SO4) and evaporated in vacuo. The crude product was chromatographed on silica gel using ethyl acetate/methanol (2:1) as eluant to afford the title product as a clear liquid (4 g). δ(CDCl3) 1.90-2.70 (2H, m, CH2); 2.80 (3H, s, CH3) 3.20-3.60 (3H, m, CH and CH2); 3.70 (3H, s, CO2CH3). After 0.75 hours extracted with dichloromethane (3×150 ml) The combined extracts were dried (Na2SO4) evaporated in vacuo The crude product was chromatographed on silica gel

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

実験手順: A 250 mL round-bottomed flask was charged with methyl 1-methyl-2-oxopyrrolidine-3-carboxylate (1.89 g, 12.0 mmol), potassium trimethylsilanolate (4.64 g, 36.1 mmol), and THF (100 mL). The reaction mixture was stirred at room temperature overnight, then HCl (50 mL, 2.0 M in Et2O) was added and the reaction mixture was stirred for 5 minutes. The solid was removed by filtration and the filtrate concentrated to give the crude product 1.28 g (74.2%), which was used in the next step without further purification. 1H NMR (400 MHz, CDCl3) δ 3.40-3.49 (m, 3H), 2.94 (s, 3H), 2.37-2.47 (m, 2H). the reaction mixture was stirred for 5 minutes The solid was removed by filtration the filtrate concentrated

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

実験手順: A 250 mL round-bottomed flask was charged with methyl 1-methyl-2-oxopyrrolidine-3-carboxylate (1.89 g, 12.0 mmol), potassium trimethylsilanolate (4.64 g, 36.1 mmol), and THF (100 mL). The reaction mixture was stirred at room temperature overnight, then HCl (50 mL, 2.0 M in Et2O) was added and the reaction mixture was stirred for 5 minutes. The solid was removed by filtration and the filtrate concentrated to give the crude product 1.28 g (74.2%), which was used in the next step without further purification. 1H NMR (400 MHz, CDCl3) δ 3.40-3.49 (m, 3H), 2.94 (s, 3H), 2.37-2.47 (m, 2H). the reaction mixture was stirred for 5 minutes The solid was removed by filtration the filtrate concentrated

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

実験手順: A 250 mL round-bottomed flask was charged with methyl 1-methyl-2-oxopyrrolidine-3-carboxylate (1.89 g, 12.0 mmol), potassium trimethylsilanolate (4.64 g, 36.1 mmol), and THF (100 mL). The reaction mixture was stirred at room temperature overnight, then HCl (50 mL, 2.0 M in Et2O) was added and the reaction mixture was stirred for 5 minutes. The solid was removed by filtration and the filtrate concentrated to give the crude product 1.28 g (74.2%), which was used in the next step without further purification. 1H NMR (400 MHz, CDCl3) δ 3.40-3.49 (m, 3H), 2.94 (s, 3H), 2.37-2.47 (m, 2H). the reaction mixture was stirred for 5 minutes The solid was removed by filtration the filtrate concentrated

反応条件: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A 250 mL round-bottomed flask was charged with 1-methylpyrrolidin-2-one (5.05 mL, 52.5 mmol), LDA (43.8 mL, 78.8 mmol, 1.8 M), and THF (125 mL). The reaction mixture stirred at −78° C. for 1 hour. Methyl chloroformate (6.06 mL, 78.8 mmol), was added, and the reaction mixture was stirred at room temperature until LC-MS showed that the starting material had been consumed (4 hours). Water (125 mL) was added, and the aqueous layer was extracted with EtOAc (3×250 mL). The combined organic layers were dried over Na2SO4 and concentrated to afford the crude product 7.35 g (89%), which was used in the next step without further purification. 1H NMR (400 MHz, CDCl3) δ 3.37 (s, 3H), 3.28-3.25 (m, 2H), 2.85 (s, 3H), 2.62-2.67 (m, 1H), 2.13-2.22 (m, 1H), 1.99-2.06 (m, 1H). the reaction mixture was stirred at room temperature until LC-MS had been consumed (4 hours) Water (125 mL) was added the aqueous layer was extracted with EtOAc (3×250 mL) The combined organic layers were dried over Na2SO4 concentrated

反応条件: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A 250 mL round-bottomed flask was charged with 1-methylpyrrolidin-2-one (5.05 mL, 52.5 mmol), LDA (43.8 mL, 78.8 mmol, 1.8 M), and THF (125 mL). The reaction mixture stirred at −78° C. for 1 hour. Methyl chloroformate (6.06 mL, 78.8 mmol), was added, and the reaction mixture was stirred at room temperature until LC-MS showed that the starting material had been consumed (4 hours). Water (125 mL) was added, and the aqueous layer was extracted with EtOAc (3×250 mL). The combined organic layers were dried over Na2SO4 and concentrated to afford the crude product 7.35 g (89%), which was used in the next step without further purification. 1H NMR (400 MHz, CDCl3) δ 3.37 (s, 3H), 3.28-3.25 (m, 2H), 2.85 (s, 3H), 2.62-2.67 (m, 1H), 2.13-2.22 (m, 1H), 1.99-2.06 (m, 1H). the reaction mixture was stirred at room temperature until LC-MS had been consumed (4 hours) Water (125 mL) was added the aqueous layer was extracted with EtOAc (3×250 mL) The combined organic layers were dried over Na2SO4 concentrated