反应详情

温度

110 °C

Into a 500 ml 3-neck round bottom flask equipped with mechanical stirrer, nitrogen atmosphere, thermocouple, heating mantle and condensor was charged the product of Example 73B (28.1 g, 165 mols), phenoxycarbonyl-(L)-valine-(41.5 g,. 165 mol) and 155 ml toluene. This solution was warmed to reflux (110° C.) and stirred for three hours, then cooled to 20°±5° C. and washed with 2×69 ml 10% citric acid followed by 1×69 ml water, 1×116 mls 4% sodium hydroxide, 1×58 ml 4% sodium hydroxide and finally 1×58 ml water. The organic product solution was then treated with 3 grams of activated carbon at reflux for 15 minutes, filtered through infusorial earth to remove carbon, and the carbon/infusorial earth cake was washed with 25 ml hot toluene. Next the solvent was removed to afford a brown oil which solidifed upon cooling. This brown solid was dissolved with warming in 31 ml EtOAc and 257 ml heptane at 60°±5° C. This solution was slowly cooled to 25° C., stirred 12 hours, cooled further to 0° C., and stirred 3 hours. The crystals were collected by filtration and washed with 50 ml 1:9 EtOAc/Heptane. The solid was dried in a 50° C. vacuum oven for 12 hours to afford 41.5 grams of the desired product as a tan-colored solid (76.9%).

1. customInto a 500 ml 3-neck round bottom flask equipped with mechanical stirrer
2. temperaturenitrogen atmosphere, thermocouple, heating mantle
3. temperatureThis solution was warmed
4. temperaturecooled to 20°±5° C.
5. washwashed with 2×69 ml 10% citric acid
6. additionThe organic product solution was then treated with 3 grams of activated carbon
7. temperatureat reflux for 15 minutes
8. filtrationfiltered through infusorial earth
9. customto remove carbon
10. washthe carbon/infusorial earth cake was washed with 25 ml hot toluene
11. customNext the solvent was removed
12. customto afford a brown oil which
13. temperatureupon cooling
14. dissolutionThis brown solid was dissolved
15. customat 60°±5° C
16. temperatureThis solution was slowly cooled to 25° C.
17. stirringstirred 12 hours
18. temperaturecooled further to 0° C.
19. stirringstirred 3 hours
20. filtrationThe crystals were collected by filtration
21. washwashed with 50 ml 1:9 EtOAc/Heptane
22. customThe solid was dried in a 50° C. vacuum oven for 12 hours