ethyl 2-(dimethylamino)-2-oxoacetate

反応条件: temp:0.00; pressure:0.00; stir:

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

実験手順: 5-Bromo-2-fluoro-pyridine (1 g, 5.68 mmol) in THF (1 mL) was added dropwise to a freshly prepared solution of lithium N,N-diisopropylamide (6.81 mmol) in THF at −78° C. The mixture was stirred 2 h at −78° C. The orange suspension was quickly added via cannula to a cold (−78° C.) solution of N,N-dimethyl-oxalamic acid ethyl ester (925.6 μL 6.81 mmol). After 1.5 h at −78° C., the reaction was quenched by addition of saturated NH4Cl solution and was allowed to warm to room temperature. The mixture was extracted with diethyl ether and the product was purified by silica gel chromoatography using hexanes and ethyl acetate (0-100% gradient) to afford 2-(5-bromo-2-fluoro-pyridin-3-yl)-N,N-dimethyl-2-oxo-acetamide (1.01 g, 65.1%). 1H NMR (500 MHz, DMSO-d6) δ 3.0 (d, 6H), 8.6 (dd, 1H), 8.78 (dd, 1H) MS: m/z 275 (M+H+). After 1.5 h at −78° C. the reaction was quenched by addition of saturated NH4Cl solution to warm to room temperature The mixture was extracted with diethyl ether the product was purified by silica gel chromoatography

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: In a 1,500 mL reactor, are added at 0° C., 360 g (4 mol) of dimethylamine (DMA) solution at 50% by weight in methanol and 44 g (0.2 mol) of sodium methylate at 25% by weight in methanol. To this mixture are added at 0-5° C. and within 1 hour, 584 g (4 mol) of diethyl oxalate. The mixture is maintained with stirring at 0° C. for 4 hours. The reaction medium is concentrated in vacuo (Pmax=200 mbars) for removing residual DMA and methanol and an 85% orthophosphoric acid solution (23.3 g 0.2 mol) is then added. The salts formed are filtered and the filtrate is then distilled in vacuo (Tbp=77-78° C., P<1 mbar) for recovering the desired product (500 g). In a 1,500 mL reactor, are added at 0° C. To this mixture are added at 0-5° C. and within 1 hour The mixture is maintained The reaction medium is concentrated in vacuo (Pmax=200 mbars) for removing residual DMA and methanol The salts formed are filtered the filtrate is then distilled in vacuo (Tbp=77-78° C., P<1 mbar) for recovering the desired product (500 g)

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

実験手順: 5-Bromo-2-fluoro-pyridine (1 g, 5.68 mmol) in THF (1 mL) was added dropwise to a freshly prepared solution of lithium N,N-diisopropylamide (6.81 mmol) in THF at −78° C. The mixture was stirred 2 h at −78° C. The orange suspension was quickly added via cannula to a cold (−78° C.) solution of N,N-dimethyl-oxalamic acid ethyl ester (925.6 uL 6.81 mmol). After 1.5 h at −78° C., the reaction was quenched by addition of saturated NH4Cl solution and was allowed to warm to room temperature. The mixture was extracted with diethyl ether and the product was purified by silica gel chromatography using hexanes and ethyl acetate (0-100% gradient) to afford 2-(5-bromo-2-fluoro-pyridin-3-yl)-N,N-dimethyl-2-oxo-acetamide (1.01 g, 65.1%). 1H NMR (500 MHz, DMSO-d6) δ 3.0 (d, 6H), 8.6 (dd, 1H), 8.78 (dd, 1H) MS: m/z 275 (M+H+). After 1.5 h at −78° C. the reaction was quenched by addition of saturated NH4Cl solution to warm to room temperature The mixture was extracted with diethyl ether the product was purified by silica gel chromatography

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: In a 1,500 mL reactor, are added at 0° C., 360 g (4 mol) of dimethylamine (DMA) solution at 50% by weight in methanol and 44 g (0.2 mol) of sodium methylate at 25% by weight in methanol. To this mixture are added at 0-5° C. and within 1 hour, 584 g (4 mol) of diethyl oxalate. The mixture is maintained with stirring at 0° C. for 4 hours. The reaction medium is concentrated in vacuo (Pmax=200 mbars) for removing residual DMA and methanol and an 85% orthophosphoric acid solution (23.3 g 0.2 mol) is then added. The salts formed are filtered and the filtrate is then distilled in vacuo (Tbp=77-78° C., P<1 mbar) for recovering the desired product (500 g). In a 1,500 mL reactor, are added at 0° C. To this mixture are added at 0-5° C. and within 1 hour The mixture is maintained The reaction medium is concentrated in vacuo (Pmax=200 mbars) for removing residual DMA and methanol The salts formed are filtered the filtrate is then distilled in vacuo (Tbp=77-78° C., P<1 mbar) for recovering the desired product (500 g)

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

実験手順: 5-Bromo-2-fluoro-pyridine (1 g, 5.68 mmol) in THF (1 mL) was added dropwise to a freshly prepared solution of lithium N,N-diisopropylamide (6.81 mmol) in THF at −78° C. The mixture was stirred 2 h at −78° C. The orange suspension was quickly added via cannula to a cold (−78° C.) solution of N,N-dimethyl-oxalamic acid ethyl ester (925.6 μL 6.81 mmol). After 1.5 h at −78° C., the reaction was quenched by addition of saturated NH4Cl solution and was allowed to warm to room temperature. The mixture was extracted with diethyl ether and the product was purified by silica gel chromoatography using hexanes and ethyl acetate (0-100% gradient) to afford 2-(5-bromo-2-fluoro-pyridin-3-yl)-N,N-dimethyl-2-oxo-acetamide (1.01 g, 65.1%). 1H NMR (500 MHz, DMSO-d6) δ 3.0 (d, 6H), 8.6 (dd, 1H), 8.78 (dd, 1H) MS: m/z 275 (M+H+). After 1.5 h at −78° C. the reaction was quenched by addition of saturated NH4Cl solution to warm to room temperature The mixture was extracted with diethyl ether the product was purified by silica gel chromoatography

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: In a 1,500 mL reactor, are added at 0° C., 360 g (4 mol) of dimethylamine (DMA) solution at 50% by weight in methanol and 44 g (0.2 mol) of sodium methylate at 25% by weight in methanol. To this mixture are added at 0-5° C. and within 1 hour, 584 g (4 mol) of diethyl oxalate. The mixture is maintained with stirring at 0° C. for 4 hours. The reaction medium is concentrated in vacuo (Pmax=200 mbars) for removing residual DMA and methanol and an 85% orthophosphoric acid solution (23.3 g 0.2 mol) is then added. The salts formed are filtered and the filtrate is then distilled in vacuo (Tbp=77-78° C., P<1 mbar) for recovering the desired product (500 g). In a 1,500 mL reactor, are added at 0° C. To this mixture are added at 0-5° C. and within 1 hour The mixture is maintained The reaction medium is concentrated in vacuo (Pmax=200 mbars) for removing residual DMA and methanol The salts formed are filtered the filtrate is then distilled in vacuo (Tbp=77-78° C., P<1 mbar) for recovering the desired product (500 g)