反应详情

N-carbobenzoxy-β-benzyl-L-aspartic acid (12 Kg) and p-nitrophenol (5.1 Kg) are dissolved in ethyl acetate (20-30 L) and the solution is cooled to below 5° C. Dicyclohexyl-carbodiimide (7.6 Kg) is dissolved in ethyl acetate (8-12 L) and added, maintaining the temperature below 5° C. The solution is stirred at reduced temperature for two hours and then for three hours at 20°-30° C. The dicyclohexylurea byproduct is removed by filtration and washed with ethyl acetate (20-30 L). The filtrate is concentrated in vacuo below 60° C. The concentrate is dissolved in a mixture of hot isopropyl alcohol (25-40 L) and distilled water (2-5 L) and cooled below 25° C. The solids are collected on a filter, rinsed with isopropyl alcohol and dried below 40° C. Melting point=76°-79° C.; specific rotation=-15° to 18° (C=1, DMF).

1. temperaturethe solution is cooled to below 5° C
2. additionadded
3. temperaturemaintaining the temperature below 5° C
4. waitfor three hours at 20°-30° C
5. customThe dicyclohexylurea byproduct is removed by filtration
6. washwashed with ethyl acetate (20-30 L)
7. concentrationThe filtrate is concentrated in vacuo below 60° C
8. dissolutionThe concentrate is dissolved in a mixture of hot isopropyl alcohol (25-40 L)
9. distillationdistilled water (2-5 L)
10. temperaturecooled below 25° C
11. customThe solids are collected on a filter
12. washrinsed with isopropyl alcohol
13. customdried below 40° C
14. customspecific rotation=-15° to 18° (C=1, DMF)