反応 #42553

反応方程式

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

収率 84.0%

溶媒

THF

THF

反応条件

後処理

1. 1
   温度to warm to ambient temperature overnight
2. 2
   その他It was quenched with saturated aqueous NH4Cl
3. 3
   抽出extracted with ethyl ether
4. 4
   洗浄The organic phase was washed with aqueous saturated NH4Cl, 1 N NaHCO3, and brine
5. 5
   乾燥It was dried over anhydrous Na2SO4
6. 6
   濃縮concentrated 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
   温度the mixture was refluxed for 2 h
10. 10
    ろ過The mixture was filtered
11. 11
    洗浄washing with methanol and dichloromethane
12. 12
    洗浄the resin was washed with 100 mL of 1:1 concentrated NH4OH
13. 13
    濃縮The 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
    濃縮It was concentrated
16. 16
    抽出extracted with ether
17. 17
    洗浄the ether was washed with several portions of water and brine
18. 18
    乾燥Drying over Na2SO4 and concentration

実験手順

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).

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