反应详情

To a solution of (5R)-5-(4,5-diphenyloxazol-2-yl)pyrrolidin-2-one (12 g) in tetrahydrofuran (THF) (200 ml) were added butyllithium (26 ml, 1.6N solution in hexane) and benzyloxycarbonyl chloride (6.8 ml) at −78° C. under N2. The mixture was stirred for 1 hour at the same temperature and partitioned between ethyl acetate and water. The organic layer was washed with 1N-HCl, water, sat. NaHCO3 and brine. The dried solvent was evaporated in vacuo, the residue was dissolved in THF (200 ml), and 1N-NaOH (87 ml) was added at 0° C. After being stirred for 12 hours at room temperature, the solvent was evaporated in vacuo. After the residue was partitioned between hexane and water, aqueous layer was adjusted to pH=2 and extracted with ethyl acetate. The organic layer was washed with water, sat. NaHCO3 and brine. The dried solvent was evaporated in vacuo and the residue was dissolved in THF (200 ml). To the solution were added triethylamine (9.0 ml) and ethyl chloroformate (5.0 ml) at −5° C. under N2 and the mixture was stirred for 1 hour at the same temperature. After the filtration, the solution was dropwise added to the solution of NaBH4 (3.2 g) in a mixture of THF (100 ml) and water (100 ml) at 0° C. and stirred for 1 hour. The mixture was partitioned between ethyl acetate and water. The organic layer was washed with 1N-HCl, sat. NaHCO3 and brine. The dried solvent was evaporated in vacuo and the residue was purified by chromatography on silica gel to give (1R)-N-benzyloxycarbonyl-4-hydroxy-1-(4,5-diphenyloxazol-2-yl)butylamine (13 g).

1. custompartitioned between ethyl acetate and water
2. washThe organic layer was washed with 1N-HCl, water, sat. NaHCO3 and brine
3. customThe dried solvent was evaporated in vacuo
4. dissolutionthe residue was dissolved in THF (200 ml)
5. addition1N-NaOH (87 ml) was added at 0° C
6. stirringAfter being stirred for 12 hours at room temperature
7. customthe solvent was evaporated in vacuo
8. customAfter the residue was partitioned between hexane and water, aqueous layer
9. extractionextracted with ethyl acetate
10. washThe organic layer was washed with water, sat. NaHCO3 and brine
11. customThe dried solvent was evaporated in vacuo
12. dissolutionthe residue was dissolved in THF (200 ml)
13. additionTo the solution were added triethylamine (9.0 ml) and ethyl chloroformate (5.0 ml) at −5° C. under N2
14. stirringthe mixture was stirred for 1 hour at the same temperature
15. filtrationAfter the filtration
16. additionthe solution was dropwise added to the solution of NaBH4 (3.2 g) in a mixture of THF (100 ml) and water (100 ml) at 0° C.
17. stirringstirred for 1 hour
18. customThe mixture was partitioned between ethyl acetate and water
19. washThe organic layer was washed with 1N-HCl, sat. NaHCO3 and brine
20. customThe dried solvent was evaporated in vacuo
21. customthe residue was purified by chromatography on silica gel