2-[2-hydroxyethyl(methyl)amino]ethanol

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:45.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a 500 ml three-necked round-bottomed flask equipped with an internal thermometer, reflux condenser, mechanical stirrer, addition funnel, and argon inlet are added N-methyldiethanolamine (20.00 g, 0.168 mol), toluene (200 ml), and triethylamine (37.36 g, 0.369 mol). The mixture is treated with a solution of phenylchloroformate (52.56 g, 0.336 mol) dissolved in 50 ml of toluene so as to maintain the reaction temperature at 35°-45° C. After addition is complete, the mixture is heated at 45° C. for an additional 1.5 h. The cooled mixture is washed with saturated sodium bicarbonate solution (2×200 ml) and water (200 ml). The organic phase is dried over MgSO4, filtered, and concentrated first by rotary evaporation at 50° C. (water aspirator vacuum) and then at 80° C. (0.02 mmHg) in a Kugelrohr oven to give 3 as a light yellow oil, 55.65 g (92%) that crystallizes on standing. Preparation of N,N-Bis[2-((phenoxycarbonyl)oxy)ethyl]-N,N-dimethylammonium Methylsulfate (4). To a 1000 ml three-necked round-bottomed flask fitted with a reflux condenser, magnetic stirrer, internal thermometer, addition funnel, and argon inlet are added N,N-bis[2-((phenoxycarbonyl)oxy)ethyl]-N-methylamine (100.00 g, 0.278 mol), acetonitrile (270 ml), and dimethylsulfate (35.93 g, 0.278 mol) over 10 min. After addition is complete, the mixture is heated to reflux for 2 h. The cooled mixture is treated with ether (500 ml). The product precipitates from the mixture after approximately 15 min to give 4 as a white powder, 126.26 g (93%): mp 85°-87° C. To a 500 ml three-necked round-bottomed flask equipped with an internal thermometer reflux condenser, mechanical stirrer, addition funnel, and argon inlet to maintain the reaction temperature at 35°-45° C After addition The cooled mixture is washed with saturated sodium bicarbonate solution (2×200 ml) and water (200 ml) The organic phase is dried over MgSO4 filtered concentrated first by rotary evaporation at 50° C. (water aspirator vacuum)

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

実験手順: Dimethyl di (βhydroxyethyl) ammonium para-toluene sulfonate (A) is prepared from methyl diethanolamine being added slowly and with stirring to methyl para-toluene sulfonate. Product (A) is rinsed and dried under slightly lowered pressure. added slowly Product (A) is rinsed dried under slightly lowered pressure

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

実験手順: Carbon dioxide was introduced into a mixture of 305.5 g of N-methyldiethanolamine (2.28 mol) and 47 g of water (1.68 mol) while the mixture was cooled with ice. 33.7 g of CO2 (0.74 mol) had been absorbed at this temperature after 3 days. was cooled with ice

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

実験手順: Here, 123 g of 2-methoxyaniline, 120 g of N-methyl-2,2'-iminodiethanol and 119 g of sulfuric acid, 100% strength, were employed. After a nitrogen pressure of 2 bar had been applied (final pressure 4.8 bar), the autoclave was kept at 160° C. for 15 h. Again, work-up was carried out as described in Example 1. 52.71 g of unreacted 2-methoxyaniline (bp. 740 to 80° C. at 1.3 to 1.7 mbar; Vigreux column 10 cm) and 52.1 g of N-methyl-N'-(2-methoxyphenyl)-piperazine (bp. 113° to 127° C. at 2.0 to 2.2 mbar) were obtained.

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

実験手順: Here, 123 g of 2-methoxyaniline, 120 g of N-methyl-2,2'-iminodiethanol and 119 g of sulfuric acid, 100% strength, were employed. After a nitrogen pressure of 2 bar had been applied (final pressure 4.8 bar), the autoclave was kept at 160° C. for 15 h. Again, work-up was carried out as described in Example 1. 52.71 g of unreacted 2-methoxyaniline (bp. 740 to 80° C. at 1.3 to 1.7 mbar; Vigreux column 10 cm) and 52.1 g of N-methyl-N'-(2-methoxyphenyl)-piperazine (bp. 113° to 127° C. at 2.0 to 2.2 mbar) were obtained.

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

実験手順: Experimental Procedure: Triphenylphosphine (77.0 mg, 0.29 mmol) and DIAD (60.0 mg, 0.29 mmol) were dissolved to a 1:1 mixture of THF and toluene (2 mL); then mono-demethylated piperlongumine (40.0 mg, 0.13 mmol) was added. After 10 min, N-methyldiethanolamine (120 mg, 0.06 mmol) was added to the mixture; the reaction was stirred at room temperature for 3 h. At the end, the solvent was evaporated under vacuum. The crude product was purified by preparative TLC(CH2Cl2/MeOH=9/1) to afford the desired product in 78% yield. At the end, the solvent was evaporated under vacuum The crude product was purified by preparative TLC(CH2Cl2/MeOH=9/1)

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

実験手順: Experimental Procedure: Triphenylphosphine (77.0 mg, 0.29 mmol) and DIAD (60.0 mg, 0.29 mmol) were dissolved to a 1:1 mixture of THF and toluene (2 mL); then mono-demethylated piperlongumine (40.0 mg, 0.13 mmol) was added. After 10 min, N-methyldiethanolamine (120 mg, 0.06 mmol) was added to the mixture; the reaction was stirred at room temperature for 3 h. At the end, the solvent was evaporated under vacuum. The crude product was purified by preparative TLC(CH2Cl2/MeOH=9/1) to afford the desired product in 78% yield. At the end, the solvent was evaporated under vacuum The crude product was purified by preparative TLC(CH2Cl2/MeOH=9/1)

反応条件: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: In a 250 ml bottle equipped with a magnetic stirrer, heating mantel, temperature controller, and dry nitrogen purge, was added DESMODUR™ N-3300 (N3300) (13.19 g, 0.020 mole, 0.068 equivalent), FBSEE (1.885 g, 0.00487 mole, 0.00974 equivalent), bicine (HOCH2CH2)2NCH2COOH) (0.815 g, 0.0050 mole, 0.010 equivalent —OH, 0.0050 equivalent —COOH), 4 drops of dibutyltin dilaurate, and 30 g N-methylpyrrolidone. The resulting mixture was stirred and heated at 70° C. for one hour, followed by addition of MeFBSE (9.996 g, 0.028 mole, 0.028 equivalent), and glycolic acid (1.368 g, 0.018 mole, 0.018 equivalent). The resulting reaction mixture was heated for another hour at 70° C., followed by addition of APTMS (0.442 g, 0.0025 mole, 0.0025 equivalent) and heated with stirring at 70° C. for an additional two hours. A 5 g portion of the resulting unneutralized chemical composition was taken for GPC analysis, and the remaining composition was cooled to 60° C. and then neutralized by adding to the composition an amount of methyldiethanolamine equivalent to the number of equivalents of carboxylic acid groups present. After 10 minutes at 60° C. the mixture was cooled and a portion of the resulting neutralized chemical composition was diluted with water to form an aqueous solution containing 3% by weight of the chemical composition. The 3% aqueous solution was evaluated for performance using Test Method I, and the results are shown in Table 3. The GPC analysis, conducted according to Test Method III, showed that the unneutralized chemical composition was comprised of components having a weight average molecular weight (Mw) of 22,183, a number average molecular weight (Mn) of 4,553, and a polydispersity (Mw/Mn) of 4.872. thus indicating the presence of both high and low molecular weight components. In a 250 ml bottle equipped with a magnetic stirrer heating mantel, temperature controller, and dry nitrogen purge was added DESMODUR™ The resulting reaction mixture was heated for another hour at 70° C. followed by addition of APTMS (0.442 g, 0.0025 mole, 0.0025 equivalent) heated with stirring at 70° C. for an additional two hours the remaining composition was cooled to 60° C. After 10 minutes at 60° C. the mixture was cooled to form an aqueous solution containing 3% by weight of the chemical composition

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

実験手順: A solution of N-methyldiethanolamine (3 g, 25 mmol) in CH2Cl2 (5 mL) was slowly added dropwise to thionyl chloride (10 mL) in ice-water bath, then stirred at r. t. for 2 days. After evaporated, the residue was dispersed with CH3 CN/Et2O, then was filtered to give N,N-bis(2-chloroethyl)methyl ammonium hydrochloride (4.1 g, 85%). After evaporated the residue was dispersed with CH3 CN/Et2O was filtered

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

実験手順: A solution of N-methyldiethanolamine (3 g, 25 mmol) in CH2Cl2 (5 mL) was slowly added dropwise to thionyl chloride (10 mL) in ice-water bath, then stirred at r. t. for 2 days. After evaporated, the residue was dispersed with CH3 CN/Et2O, then was filtered to give N,N-bis(2-chloroethyl)methyl ammonium hydrochloride (4.1 g, 85%). After evaporated the residue was dispersed with CH3 CN/Et2O was filtered

反応条件: temp:45.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a 500 ml three-necked round-bottomed flask equipped with an internal thermometer, reflux condenser, mechanical stirrer, addition funnel, and argon inlet are added N-methyldiethanolamine (20.00 g, 0.168 mol), toluene (200 ml), and triethylamine (37.36 g, 0.369 mol). The mixture is treated with a solution of phenylchloroformate (52.56 g, 0.336 mol) dissolved in 50 ml of toluene so as to maintain the reaction temperature at 35°-45° C. After addition is complete, the mixture is heated at 45° C. for an additional 1.5 h. The cooled mixture is washed with saturated sodium bicarbonate solution (2×200 ml) and water (200 ml). The organic phase is dried over MgSO4, filtered, and concentrated first by rotary evaporation at 50° C. (water aspirator vacuum) and then at 80° C. (0.02 mmHg) in a Kugelrohr oven to give 3 as a light yellow oil, 55.65 g (92%) that crystallizes on standing. Preparation of N,N-Bis[2-((phenoxycarbonyl)oxy)ethyl]-N,N-dimethylammonium Methylsulfate (4). To a 1000 ml three-necked round-bottomed flask fitted with a reflux condenser, magnetic stirrer, internal thermometer, addition funnel, and argon inlet are added N,N-bis[2-((phenoxycarbonyl)oxy)ethyl]-N-methylamine (100.00 g, 0.278 mol), acetonitrile (270 ml), and dimethylsulfate (35.93 g, 0.278 mol) over 10 min. After addition is complete, the mixture is heated to reflux for 2 h. The cooled mixture is treated with ether (500 ml). The product precipitates from the mixture after approximately 15 min to give 4 as a white powder, 126.26 g (93%): mp 85°-87° C. To a 500 ml three-necked round-bottomed flask equipped with an internal thermometer reflux condenser, mechanical stirrer, addition funnel, and argon inlet to maintain the reaction temperature at 35°-45° C After addition The cooled mixture is washed with saturated sodium bicarbonate solution (2×200 ml) and water (200 ml) The organic phase is dried over MgSO4 filtered concentrated first by rotary evaporation at 50° C. (water aspirator vacuum)