反应详情

Cool a solution of lithium aluminum hydride (450 mL, 1M in tetrahydrofuran, 450 mmol) to -10° C. in a ice/acetone bath. Add dropwise, a solution of sulfuric acid (12 mL, 99.999%, 225.3 mmol) in tetrahydrofuran (35 mL). (Use caution when adding the sulfuric acid to the tetrahydrofuran and also when adding the sulfuric acid/tetrahydrofuran solution to the lithium aluminum hydride solution). After the addition is complete, stir for 1 hour. Warm to ambient temperature and stir for 2 hours. Add dropwise, a solution of (3-(3,4-dichlorophenyl)-5-oxopyrrolidin-3-yl)acetic acid ethyl ester (23.2 g, 73.4 mmol) in tetrahydrofuran (70 mL). Heat to 45°-50° C. for 36 hours. Cool in an ice bath. Add dropwise, a solution of tetrahydrofuran/water (1/1, 70 mL). Filter and rinse the filter cake with Tetrahydrofuran and dichloromethane, retain the filtrate. Combine the filter cake with tetrahydrofuran/water/15% sodium hydroxide solution (1 L/70 mL/20 mL) and vigorously stir for 2 hours. Filter and combine the filtrate with the filtrate obtained above. Concentrate the combined filtrates invacuo to obtain a residue. Dissolve the residue in dichloromethane and dry over MgSO4, filter, and concentrate invacuo to obtain a residue. Recrystallize the residue from diethyl ether to give the title compound: Rf= 0.27 (silica gel, 9/1/0.2 dichloromethane/methanol/ammonium hydroxide); mp; 91°-94° C.

1. additionAdd dropwise
2. additionAfter the addition
3. stirringstir for 2 hours
4. additionAdd dropwise
5. temperatureHeat to 45°-50° C. for 36 hours
6. temperatureCool in an ice bath
7. additionAdd dropwise
8. filtrationFilter
9. washrinse the filter cake with Tetrahydrofuran and dichloromethane
10. stirringvigorously stir for 2 hours
11. filtrationFilter
12. customobtained above
13. concentrationConcentrate the combined filtrates
14. customto obtain a residue
15. dry with materialdry over MgSO4
16. filtrationfilter
17. concentrationconcentrate invacuo
18. customto obtain a residue
19. customRecrystallize the residue from diethyl ether