반응 #1567745

반응 방정식

tert-butyl 5-methoxy-2,2-dimethylpyrrolidine-1-carboxylate

(R)-4-benzyl-3-(2-(4-chlorophenyl)acetyl)oxazolidin-2-one

diisopropylethylamine

DIBAL-H

tert-Butyl 2,2-dimethyl-5-oxopyrrolidine-1-carboxylate

→

(S)-tert-butyl 5-((S)-2-((R)-4-benzyl-2-oxooxazolidin-3-yl)-1-(4-chlorophenyl)-2-oxoethyl)-2,2-dimethylpyrrolidine-1-carboxylate

수율 61.3%

용매

dichloromethane

toluene

dichloromethane

Et2O

반응 조건

후처리

1. 1
   온도warmed to ambient temperature overnight
2. 2
   기타The reaction was quenched by addition of an aliquot (7 mL) of a solution of p-toluenesulfonic acid hydrate (0.012 g) in MeOH (12 mL)
3. 3
   workup.STIRRINGThe mixture was stirred at ambient temperature for 60 hours
4. 4
   농축The suspension was concentrated in vacuo
5. 5
   workup.ADDITIONre-suspended in a mixture of Rochelle's salt (0.5N) and ethyl acetate
6. 6
   기타After separation
7. 7
   세척the aqueous portion was washed with ethyl acetate (2×)
8. 8
   세척The combined organics were then washed with saturated NaCl
9. 9
   건조dried over Na2SO4
10. 10
    농축concentrated in vacuo to a light oil (92%)
11. 11
    workup.WAITAfter 5 minutes
12. 12
    온도cooled to −20° C
13. 13
    workup.STIRRINGthe mixture was stirred at −20° C. for 75 minutes
14. 14
    기타The reaction was quenched with saturated NH4Cl (about 4 mL)
15. 15
    workup.ADDITIONdiluted with water
16. 16
    workup.DISSOLUTIONto dissolve the solids
17. 17
    기타After separation
18. 18
    세척the aqueous portion was washed with methylene chloride (3×)
19. 19
    세척The combined organics were washed with water (2×)
20. 20
    건조dried over Na2SO4
21. 21
    농축concentrated in vacuo
22. 22
    세척eluted with 9:1 hexanes/ethyl acetate

실험 절차

tert-Butyl 2,2-dimethyl-5-oxopyrrolidine-1-carboxylate (1.170 g, 5.4859 mmol) was dissolved in Et2O (15 mL) and cooled to −78° C. The solution was treated with DIBAL-H (3.7304 mL, 5.5956 mmol). The mixture was stirred at −78° C. for 2 hours and then warmed to ambient temperature overnight. The reaction was quenched by addition of an aliquot (7 mL) of a solution of p-toluenesulfonic acid hydrate (0.012 g) in MeOH (12 mL). The mixture was stirred at ambient temperature for 60 hours. The suspension was concentrated in vacuo and re-suspended in a mixture of Rochelle's salt (0.5N) and ethyl acetate. After separation, the aqueous portion was washed with ethyl acetate (2×). The combined organics were then washed with saturated NaCl, dried over Na2SO4 and concentrated in vacuo to a light oil (92%). A solution of titanium(IV) chloride (3.7128 ml, 3.7128 mmol) in toluene was cooled to 0° C. and treated with a solution of (R)-4-benzyl-3-(2-(4-chlorophenyl)acetyl)oxazolidin-2-one (1.1131 g, 3.3753 mmol) dissolved in dichloromethane (7 mL). After 5 minutes, diisopropylethylamine (0.64671 mL, 3.7128 mmol) was added. The resultant solution was stirred for 1 hour at 0° C. and then cooled to −20° C. A solution of tert-butyl 5-methoxy-2,2-dimethylpyrrolidine-1-carboxylate (1.090 g, 5.0630 mmol) in dichloromethane (7 mL) was added, and the mixture was stirred at −20° C. for 75 minutes. The reaction was quenched with saturated NH4Cl (about 4 mL) and diluted with water to dissolve the solids. After separation, the aqueous portion was washed with methylene chloride (3×). The combined organics were washed with water (2×), dried over Na2SO4 and concentrated in vacuo. The crude product was subjected to chromatography on SiO2 and eluted with 9:1 hexanes/ethyl acetate to produce (S)-tert-butyl 5-((S)-2-((R)-4-benzyl-2-oxooxazolidin-3-yl)-1-(4-chlorophenyl)-2-oxoethyl)-2,2-dimethylpyrrolidine-1-carboxylate (1.09 g, 61%). MS (ESI+) [M+H] 526.7/528.8

출처