N-[2-(ethylamino)ethyl]-2,2,2-trifluoroacetamide

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

実験手順: A solution of N-ethylethylenediamine (10.0 g, 113.4 mmol) and ethyl trifluoroacetate (32.0 mL, 261 mmol) in a mixture of acetonitrile (110 mL) and water (2.5 mL, 139 mmol) was refluxed with stirring overnight (˜18 hours (hr, h)). Solvents were evaporated in vacuo. Residue was re-evaporated with isopropanol (3×100 mL). Residue was dissolved in dichloromethane (500 mL) and left overnight at room temperature (rt). The formed crystals were filtered, washed with dichloromethane (100 mL) and dried in vacuo to provide compound QQ (24.6 g, 82.4 mmol) as a white solid powder. was refluxed Solvents were evaporated in vacuo Residue was re-evaporated with isopropanol (3×100 mL) Residue was dissolved in dichloromethane (500 mL) left overnight at room temperature (rt) The formed crystals were filtered washed with dichloromethane (100 mL) dried in vacuo to provide compound QQ (24.6 g, 82.4 mmol) as a white solid powder

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

実験手順: A solution of N-ethylethylenediamine (10.0 g, 113.4 mmol) and ethyl trifluoroacetate (32.0 mL, 261 mmol) in a mixture of acetonitrile (110 mL) and water (2.5 mL, 139 mmol) was refluxed with stirring overnight (˜18 hours (hr, h)). Solvents were evaporated in vacuo. Residue was re-evaporated with isopropanol (3×100 mL). Residue was dissolved in dichloromethane (500 mL) and left overnight at room temperature (rt). The formed crystals were filtered, washed with dichloromethane (100 mL) and dried in vacuo to provide compound QQ (24.6 g, 82.4 mmol) as a white solid powder. was refluxed Solvents were evaporated in vacuo Residue was re-evaporated with isopropanol (3×100 mL) Residue was dissolved in dichloromethane (500 mL) left overnight at room temperature (rt) The formed crystals were filtered washed with dichloromethane (100 mL) dried in vacuo to provide compound QQ (24.6 g, 82.4 mmol) as a white solid powder

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

実験手順: A solution of N-ethylethylenediamine (10.0 g, 113.4 mmol) and ethyl trifluoroacetate (32.0 mL, 261 mmol) in the mixture of acetonitrile (110 mL) and water (2.5 mL, 139 mmol) was refluxed with stirring overnight (˜18 h). Solvents were evaporated in vacuo. Residue was re-evaporated with i-PrOH (3×100 mL). Residue was dissolved in dichloromethane (500 mL) and left overnight at room temperature. The formed crystals were filtered, washed with dichloromethane (100 mL) and dried in vacuo to provide compound JJ (24.6 g, 82.4 mmol) as white solid powder. was refluxed Solvents were evaporated in vacuo Residue was re-evaporated with i-PrOH (3×100 mL) Residue was dissolved in dichloromethane (500 mL) left overnight at room temperature The formed crystals were filtered washed with dichloromethane (100 mL) dried in vacuo to provide compound JJ (24.6 g, 82.4 mmol) as white solid powder

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

実験手順: A solution of compound M (24.6 g, 82.4 mmol) and DIEA (14.3 ml, 82.4 mmol) in THF (100 ml) was cooled to ˜5° C., followed by the addition of a solution of N-(benzyloxycarbonyl)succinimide (20.3 g, 81.6 mmol) in THF (75 ml) dropwise over 20 min The temperature of the reaction mixture was raised to room temperature and stirring was continued for an additional 30 min. Solvents were evaporated and the residue was dissolved in EtOAc (500 ml). The organic layer was extracted with 5% aqueous NaHCO3 (2×100 ml) and brine (100 ml). The organic layer was evaporated to provide compound N (24.9 g, 78.2 mmol) as yellowish oil. LC-MS [M+H] 319.0 (C14H17F3N2O3+H, calc: 319.2). Compound N was used without further purification. Solvents were evaporated the residue was dissolved in EtOAc (500 ml) The organic layer was extracted with 5% aqueous NaHCO3 (2×100 ml) and brine (100 ml) The organic layer was evaporated

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

実験手順: A solution of N-ethylethylenediamine (10.0 g, 113.4 mmol) and ethyl trifluoroacetate (32.0 ml, 261 mmol) in the mixture of acetonitrile (110 ml) and water (2.5 ml, 139 mmol) was refluxed with stirring overnight (˜18 h). Solvents were evaporated in vacuo. Residue was re-evaporated with i-PrOH (3×100 ml). Residue was dissolved in dichloromethane (500 ml) and left overnight at room temperature. The formed crystals were filtered, washed with dichloromethane (100 ml) and dried in vacuo to provide compound M (24.6 g, 82.4 mmol) as white solid powder. was refluxed Solvents were evaporated in vacuo Residue was re-evaporated with i-PrOH (3×100 ml) Residue was dissolved in dichloromethane (500 ml) left overnight at room temperature The formed crystals were filtered washed with dichloromethane (100 ml) dried in vacuo

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

実験手順: A solution of compound M (24.6 g, 82.4 mmol) and DIEA (14.3 ml, 82.4 mmol) in THF (100 ml) was cooled to ˜5° C., followed by the addition of a solution of N-(benzyloxycarbonyl)succinimide (20.3 g, 81.6 mmol) in THF (75 ml) dropwise over 20 min The temperature of the reaction mixture was raised to room temperature and stirring was continued for an additional 30 min. Solvents were evaporated and the residue was dissolved in EtOAc (500 ml). The organic layer was extracted with 5% aqueous NaHCO3 (2×100 ml) and brine (100 ml). The organic layer was evaporated to provide compound N (24.9 g, 78.2 mmol) as yellowish oil. LC-MS [M+H] 319.0 (C14H17F3N2O3+H, calc: 319.2). Compound N was used without further purification. Solvents were evaporated the residue was dissolved in EtOAc (500 ml) The organic layer was extracted with 5% aqueous NaHCO3 (2×100 ml) and brine (100 ml) The organic layer was evaporated

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

実験手順: A solution of N-ethylethylenediamine (10.0 g, 113.4 mmol) and ethyl trifluoroacetate (32.0 mL, 261 mmol) in a mixture of acetonitrile (110 mL) and water (2.5 mL, 139 mmol) was refluxed with stirring overnight (˜18 hours (hr, h)). Solvents were evaporated in vacuo. Residue was re-evaporated with isopropanol (3×100 mL). Residue was dissolved in dichloromethane (500 mL) and left overnight at room temperature (rt). The formed crystals were filtered, washed with dichloromethane (100 mL) and dried in vacuo to provide compound QQ (24.6 g, 82.4 mmol) as a white solid powder. was refluxed Solvents were evaporated in vacuo Residue was re-evaporated with isopropanol (3×100 mL) Residue was dissolved in dichloromethane (500 mL) left overnight at room temperature (rt) The formed crystals were filtered washed with dichloromethane (100 mL) dried in vacuo to provide compound QQ (24.6 g, 82.4 mmol) as a white solid powder

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

実験手順: A solution of N-ethylethylenediamine (10.0 g, 113.4 mmol) and ethyl trifluoroacetate (32.0 mL, 261 mmol) in the mixture of acetonitrile (110 mL) and water (2.5 mL, 139 mmol) was refluxed with stirring overnight (˜18 h). Solvents were evaporated in vacuo. Residue was re-evaporated with i-PrOH (3×100 mL). Residue was dissolved in dichloromethane (500 mL) and left overnight at room temperature. The formed crystals were filtered, washed with dichloromethane (100 mL) and dried in vacuo to provide compound JJ (24.6 g, 82.4 mmol) as white solid powder. was refluxed Solvents were evaporated in vacuo Residue was re-evaporated with i-PrOH (3×100 mL) Residue was dissolved in dichloromethane (500 mL) left overnight at room temperature The formed crystals were filtered washed with dichloromethane (100 mL) dried in vacuo to provide compound JJ (24.6 g, 82.4 mmol) as white solid powder