تفاعل #42553

معادلة التفاعل

Cyclopentyl magnesium bromide

tert-butyl (2R)-2-[(4S)-2,2-dimethyl-1,3-dioxolan-4-yl]aziridine-1-carboxylate

di-t-butyldicarbonate

→

tert-butyl (1S,2S)-1-[cyclopentylmethy]-2,3-dihydroxypropylcarbamate

المردود 84.0%

المذيبات

THF

THF

ظروف التفاعل

المعالجة

1. 1
   درجة الحرارةto warm to ambient temperature overnight
2. 2
   أخرىIt was quenched with saturated aqueous NH4Cl
3. 3
   استخلاصextracted with ethyl ether
4. 4
   غسيلThe organic phase was washed with aqueous saturated NH4Cl, 1 N NaHCO3, and brine
5. 5
   تجفيفIt was dried over anhydrous Na2SO4
6. 6
   تركيزconcentrated to 2.38 g of a solid
7. 7
   workup.DISSOLUTIONThis material was dissolved in 70 mL of methanol
8. 8
   workup.ADDITION12 g of Dowex 50WX2-400 was added
9. 9
   درجة الحرارةthe mixture was refluxed for 2 h
10. 10
    ترشيحThe mixture was filtered
11. 11
    غسيلwashing with methanol and dichloromethane
12. 12
    غسيلthe resin was washed with 100 mL of 1:1 concentrated NH4OH
13. 13
    تركيزThe filtrate was concentrated to 1.16 g of tan crystals
14. 14
    workup.DISSOLUTIONThe crystals were dissolved in 30 mL of dry THF
15. 15
    تركيزIt was concentrated
16. 16
    استخلاصextracted with ether
17. 17
    غسيلthe ether was washed with several portions of water and brine
18. 18
    تجفيفDrying over Na2SO4 and concentration

الإجراء التجريبي

Cyclopentyl magnesium bromide (8 mL of 2M ethereal solution) was added to cuprous bromide/dimethylsulfide complex (0.33 g, 1.6 mmol) in 10 mL of dry THF cooled to −25° C. under nitrogen. After 20 min, a solution of tert-butyl (2R)-2-[(4S)-2,2-dimethyl-1,3-dioxolan-4-yl]aziridine-1-carboxylate (1.95 g, 8 mmol) in 4 mL of dry THF was introduced. The mixture was allowed to warm to ambient temperature overnight. It was quenched with saturated aqueous NH4Cl and extracted with ethyl ether. The organic phase was washed with aqueous saturated NH4Cl, 1 N NaHCO3, and brine. It was dried over anhydrous Na2SO4 and concentrated to 2.38 g of a solid. This material was dissolved in 70 mL of methanol, 12 g of Dowex 50WX2-400 was added, and the mixture was refluxed for 2 h. The mixture was filtered, washing with methanol and dichloromethane. A clean receiver was attached, and the resin was washed with 100 mL of 1:1 concentrated NH4OH:ethanol. The filtrate was concentrated to 1.16 g of tan crystals. The crystals were dissolved in 30 mL of dry THF, and 1.5 g (6.9 mmol) of di-t-butyldicarbonate was introduced. The mixture was stirred under nitrogen overnight. It was concentrated, extracted with ether and the ether was washed with several portions of water and brine. Drying over Na2SO4 and concentration afforded 1.8 g (6.7 mmol, 84% from tert-butyl (2R)-2-[(4S)-2,2-dimethyl-1,3-dioxolan-4-yl]aziridine-1-carboxylate) of tert-butyl (1S,2S)-1-[cyclopentylmethy]-2,3-dihydroxypropylcarbamate: 1H NMR (CDCl3) δ 4.5 (d, 1H, NH), 3.7 (m, 1H), 3.6-3.49 (m, 2H), 3.36 (m, 1 H), 3.26 (t, 1H, OH), 2.76 (d, 1H, OH), 1.45 (s, 9H), 1.88-1.36 (m, 9H), 1.17-1.08 (m, 2H).

المصدر