反应详情

Cool a solution of lithium aluminum hydride (450 mL, 1M in THF, 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 THF (35 mL). (Use caution when adding the sulfuric acid to the THF and also when adding the sulfuric acid/THF 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 THF (70 mL). Heat to 45-50° C. for 36 hours. Cool in an ice bath. Add dropwise, a solution of THF/water (1/1, 70 mL). Filter and rinse the filter cake with THF and dichloromethane, retain the filtrate. Combine the filter cake with THF/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 in vacuo to obtain a residue. Dissolve the residue in dichloromethane and dry over MgSO4, filter, and concentrate in vacuo 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. Elemental Analysis calculated for C12H15Cl2NO: C 55.40; H 5.81; N 5.38; Found: C 55.64; H 5.88; N 5.20.

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 THF and dichloromethane
10. stirringvigorously stir for 2 hours
11. filtrationFilter
12. customobtained above
13. concentrationConcentrate the combined filtrates in vacuo
14. customto obtain a residue
15. dry with materialdry over MgSO4
16. filtrationfilter
17. concentrationconcentrate in vacuo
18. customto obtain a residue
19. customRecrystallize the residue from diethyl ether