反応 #867

反応方程式

water

HOBt

HCl dioxane

N-t-butoxycarbonyl-α,α-diethylglycine (S)-α-ethylbenzylamide

triethylamine

β-benzyl-N-benzyloxycarbonyl-L-aspartate

→

α-L-aspartyl-α,α-diethylglycine (S)-α-ethylbenzylamide

収率 29.3%

反応条件

後処理

1. 1
   濃縮The reaction mixture was concentrated under reduced pressure, 30 ml of ether
2. 2
   workup.ADDITIONwas added to the residue
3. 3
   濃縮this was again concentrated
4. 4
   workup.DISSOLUTIONThe residue was dissolved in 25 ml of methylene chloride
5. 5
   温度Under cooling
6. 6
   workup.STIRRINGthese were stirred for one hour
7. 7
   温度under cooling
8. 8
   その他overnight
9. 9
   その他at room temperature
10. 10
    濃縮The reaction mixture was concentrated under reduced pressure and 50 ml of aqueous 5% citric acid
11. 11
    workup.ADDITIONwere added
12. 12
    抽出The resulting residue was extracted two times each with 50 ml of ethyl acetate
13. 13
    洗浄washed with 20 ml of water, 25 ml of aqueous 5% sodium hydrogencarbonate and 20 ml of brine, in that order
14. 14
    乾燥The resulting organic layer was dried with anhydrous magnesium sulfate
15. 15
    ろ過filtered
16. 16
    濃縮the resulting filtrate was concentrated under reduced pressure
17. 17
    workup.DISSOLUTIONThe residue was dissolved in 30 ml of methanol
18. 18
    workup.ADDITION0.30 g of 10% Pd-carbon (water content 50) was added
19. 19
    workup.ADDITION40 ml of water was added to this, the catalyst
20. 20
    その他was removed by filtration
21. 21
    濃縮the resulting filtrate was concentrated to about 1/4
22. 22
    その他This was then stored in a refrigerator overnight
23. 23
    その他The crystal thus precipitated
24. 24
    その他was removed by filtration
25. 25
    その他dried

実験手順

19 ml of 4N-HCl/dioxane solution were added to 1.31 g (3.76 mmols) of N-t-butoxycarbonyl-α,α-diethylglycine (S)-α-ethylbenzylamide, and the mixture was stirred at room temperature for one hour. The reaction mixture was concentrated under reduced pressure, 30 ml of ether was added to the residue, and this was again concentrated. The residue was dissolved in 25 ml of methylene chloride, and 0.55 ml (4.13 mmols) of triethylamine and 1.48 g (4.13 mmols) of β-benzyl-N-benzyloxycarbonyl-L-aspartate were added thereto. Under cooling, 0.79 g (4.13 mmols) of water-soluble carbodiimide hydrochloride and 0.51 g (3.76 mmols) of HOBt were added thereto, and these were stirred for one hour under cooling and then overnight at room temperature. The reaction mixture was concentrated under reduced pressure and 50 ml of aqueous 5% citric acid were added. The resulting residue was extracted two times each with 50 ml of ethyl acetate and then washed with 20 ml of water, 25 ml of aqueous 5% sodium hydrogencarbonate and 20 ml of brine, in that order. The resulting organic layer was dried with anhydrous magnesium sulfate and filtered, and the resulting filtrate was concentrated under reduced pressure. The residue was dissolved in 30 ml of methanol, 0.30 g of 10% Pd-carbon (water content 50) was added thereto, and the mixture was reduced under hydrogen. 40 ml of water was added to this, the catalyst was removed by filtration, and the resulting filtrate was concentrated to about 1/4. This was then stored in a refrigerator overnight. The crystal thus precipitated was removed by filtration and dried to obtain 0.40 g (1.10 mmols) of α-L-aspartyl-α,α-diethylglycine (S)-α-ethylbenzylamide.

出典