N-(2-Aminoethyl)morpholine-4-carboxamide oxalate synthesis

Yield:154467-16-0 89.8%

Reaction Conditions:

Stage #1: 4-[(1H-imidazol-1-yl)carbonyl]morpholine;ethylenediamine at 64 - 70; for 7 h;Industrial scale;
Stage #2: with sodium hydroxide in acetone at 20; pH=11 - 12;Industrial scale;
Stage #3: oxalic acid in ethanol;water at 20; pH=2 - 3; for 0.5 h;Reflux;Industrial scale;Solvent;

Steps:

1; 2; 3; 4; 5 Example 1 Preparation of N-(2-aminoethyl)-4-morpholinecarboxamide oxalate

In the reactor, add 230.0kg ethylenediamine,Under stirring, 93.0kg of N-phenoxycarbonylmorpholine was added, the temperature was raised to 64-70°C, and the reaction was carried out for 6 hours.Recover ethylenediamine by distillation under reduced pressure, and when there is no liquid dripping,The temperature is controlled at 70±2°C, and the vacuum distillation is continued for 1 hour.Reduce to room temperature, add 370.0kg of acetone, add 30% sodium hydroxide solution dropwise with stirring, adjust pH 11~12, precipitate a large amount of solids, filter, and concentrate the filtrate to recover acetone. Add 350.0 kg of water to the residue, stir to dissolve, control the temperature at 20°C to 40°C, add oxalic acid solids in batches to adjust to pH 2 to 3, and precipitate a small amount of solids. Spin filtration, concentrate the filtrate to a slurry state, add 600 kg of ethanol, reflux for 0.5 hours, and filter pressure to a crystallization tank. Cool down and crystallize, keep at 0~10°C for 4 hours, filter, and dry the filter cake in a hot-air circulating oven at 50-60°C for 8 hours to obtain almost white N-(2-aminoethyl)-4-morpholinecarboxamide oxalate The solid was 106.1kg, and the yield was 89.8%. HPLC purity: 99.97%, moisture: 0.7%, ethylenediamine: 0.02%, ethanol: 7ppm.

References:

CN112898234,2021,A Location in patent:Paragraph 0005; 0021-0025