反应详情

A solution of LiAlH4 (450 mL, 1M in THF, 450 mmol) was cooled in a ice/acetone bath (-10° C.). A solution of H2SO4 (99.999%) (12 mL, 225.3 mmol) in THF (35 mL) was added dropwise. (Use caution when adding the H2SO4 to the THF and also when adding the H2SO4 /THF solution to the LiA1H4) After the addition was complete, the slurry was stirred for 1 h in an ice bath. The slurry was allowed to warm to ambient temperature and stir for 2 h. A solution of [3-(3,4-dichloro-phenyl)-5-oxo-pyrrolidin-3-yl]-acetic acid ethyl ester (23.2 g, 73.4 mmol) in THF (70 mL) was added dropwise. The slurry was heated to 45°-50° C. for 36 h. The slurry was cooled in an ice bath and a solution of THF:H2O (1:1, 70 mL) was added dropwise. The slurry was filtered and the solids were rinsed with THF and dichloromethane. The salts were stirred with THF:H2 0:15% NaOH (1 L :70 mL :20 mL) for 2 h. The slurry was filtered and the combined filtrates were concentrated in vacuo to obtain a residue. The residue was dissolved in dichloromethane and the solution was dried over MgSO4, filtered, and concentrated in vacuo to obtain a residue. The residue was recrystallized from diethyl ether to give the title compound:

1. additionAfter the addition
2. stirringstir for 2 h
3. temperatureThe slurry was heated to 45°-50° C. for 36 h
4. temperatureThe slurry was cooled in an ice bath
5. filtrationThe slurry was filtered
6. washthe solids were rinsed with THF and dichloromethane
7. stirringThe salts were stirred with THF
8. waitH2 0:15% NaOH (1 L :70 mL :20 mL) for 2 h
9. filtrationThe slurry was filtered
10. concentrationthe combined filtrates were concentrated in vacuo
11. customto obtain a residue
12. dry with materialthe solution was dried over MgSO4
13. filtrationfiltered
14. concentrationconcentrated in vacuo
15. customto obtain a residue
16. customThe residue was recrystallized from diethyl ether