反应详情

To a solution of Example 2 product (i.e., O-methyl-N-trityl-D-serine, 50 g) in ethyl acetate (500 ml), N-methyl morpholine (20.9 g) was added at −15° C. in 5-10 minutes. The reaction mixture was stirred for 15 minutes and then isobutylchloroformate (18.8 g) already diluted with tetrahydrofuran was added to it at −15° C. under nitrogen atmosphere in 15-20 minutes. The solution was stirred for 15 minutes and benzyl amine (14.7 g) was added to it at −15° C. in 15 minutes. The solution was allowed to cool to room temperature and stirred for 2 hours. The solvent was recovered from the solution. Dichloromethane (250 ml) was added to the crude product and stirred for 5 minutes to dissolve. The dichloromethane layer was washed or stirred for 5 minutes with water (250 ml). The layers were separated and the dichloromethane layer was again washed with 5% NaHCO3 (250 ml). The layers were separated and then the dichloromethane layer was sequentially washed with 5% citric acid solution (250 ml) and then with water (250 ml). The solvent was recovered at 40° C. to 45° C. to get oil. Ethyl acetate was added to the oil and the mixture was heated to 60° C. to 65° C. to dissolve. The clear solution so formed was cooled up to room temperature and then hexanes (350 ml) were added to it. It was stirred for 1 hour at room temperature, filtered and then dried to get compound of Formula Va. Yield=31 gm.

1. additionwas added to it at −15° C. under nitrogen atmosphere in 15-20 minutes
2. stirringThe solution was stirred for 15 minutes
3. stirringstirred for 2 hours
4. customThe solvent was recovered from the solution
5. additionDichloromethane (250 ml) was added to the crude product
6. stirringstirred for 5 minutes
7. dissolutionto dissolve
8. washThe dichloromethane layer was washed
9. stirringstirred for 5 minutes with water (250 ml)
10. customThe layers were separated
11. washthe dichloromethane layer was again washed with 5% NaHCO3 (250 ml)
12. customThe layers were separated
13. washthe dichloromethane layer was sequentially washed with 5% citric acid solution (250 ml)
14. customThe solvent was recovered at 40° C. to 45° C.
15. customto get oil
16. temperaturethe mixture was heated to 60° C. to 65° C.
17. dissolutionto dissolve
18. customThe clear solution so formed
19. temperaturewas cooled up to room temperature
20. stirringIt was stirred for 1 hour at room temperature
21. filtrationfiltered
22. customdried
23. customto get compound of Formula Va