Reaction #42553

Reaction equation

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

Yield 84.0%

Solvents

THF

THF

Conditions

Workup

1. 1
   Temperatureto warm to ambient temperature overnight
2. 2
   OtherIt was quenched with saturated aqueous NH4Cl
3. 3
   Extractionextracted with ethyl ether
4. 4
   WashThe organic phase was washed with aqueous saturated NH4Cl, 1 N NaHCO3, and brine
5. 5
   DryingIt was dried over anhydrous Na2SO4
6. 6
   Concentrationconcentrated 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
   Temperaturethe mixture was refluxed for 2 h
10. 10
    FiltrationThe mixture was filtered
11. 11
    Washwashing with methanol and dichloromethane
12. 12
    Washthe resin was washed with 100 mL of 1:1 concentrated NH4OH
13. 13
    ConcentrationThe 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
    ConcentrationIt was concentrated
16. 16
    Extractionextracted with ether
17. 17
    Washthe ether was washed with several portions of water and brine
18. 18
    DryingDrying over Na2SO4 and concentration

Procedure

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).

Source