反应详情

温度

60 °C

This solution containing N-(1(S)-ethoxycarbonyl-3-phenylpropyl)-L-alanyl-L-proline was added to a solution of 10.66 g (92 mmol) of maleic acid in 20 ml of H2O, with stirring at an inner temperature of 60° C. over 1 hour. The stirring was continued for 1 hour under the same conditions and, then, the inner temperature was cooled down to 5° C. over 3 hours, and the stirring was continued for further 2 hours. The deposited crystal was taken out by filtration under reduced pressure, and quickly washed three times with 80 ml of H2O cooled to 0 to 3° C. . The resulting crystal had a good filterability and a glossy and excellent crystal form; In the case of forming the salt at an inner temperature of 30° C., the resulting salt was slurry in the form of whip and had a poor filterability and a form of fine crystal. The resulting wet crystal was dried under reduced pressure (20 to 50° C., 30→1 mmHg), to obtain 42.05 g (85 mmol) of N-(1(S)-ethoxycarbonyl-3-phenylpropyl)-L-alanyl-L-proline maleate. The purity was at least 99% and the contents of the diketopiperazine derivative (3), carboxy derivative (4) and N-(1(S)-ethoxycarbonyl-3-phenylpropyl)-L-alanine (5) were respectively at most 0.05% by weight. The yield from N-(1(S)-ethoxycarbonyl-3-phenylpropyl)-L-alanine N-carboxyanhydride was 89%.

1. waitThe stirring was continued for 1 hour under the same conditions
2. temperaturethe inner temperature was cooled down to 5° C. over 3 hours
3. waitthe stirring was continued for further 2 hours
4. filtrationThe deposited crystal was taken out by filtration under reduced pressure
5. washquickly washed three times with 80 ml of H2O
6. temperaturecooled to 0 to 3° C.
7. customIn the case of forming the salt at an inner temperature of 30° C.
8. customThe resulting wet crystal was dried under reduced pressure (20 to 50° C., 30→1 mmHg)