反应详情

温度

5 °C

The obtained 12% by weight aqueous solution of N-(1(S)-ethoxycarbonyl-3-phenylpropyl)-L-alanyl-L-proline was warmed to an inner temperature of 30° C. and thereto was added 10.73 g (93 mmol) of maleic acid with stirring. 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. To the mixture was added 62.05 g of NaCl 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 wet crystal was dried under reduced pressure (20 to 50° C., 30→1 mmHg) to obtain 40.35 g (82 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 86%.

1. waitthe stirring was continued for further 2 hours
2. filtrationThe deposited crystal was taken out by filtration under reduced pressure
3. washquickly washed three times with 80 ml of H2O
4. temperaturecooled to 0 to 3° C
5. customThe resulting wet crystal was dried under reduced pressure (20 to 50° C., 30→1 mmHg)