反応 #4592

反応方程式

sodium cyanamide

DCC

N-hydroxysuccinimide

N-benzoyl-L-leucine

→

N-Benzoyl-L-leucylcyanamide

収率 42.9%

溶媒

THF

—

EtOAc petroleum ether THF CH2Cl2 AcOH

water

—

EtOAc petroleum ether AcOH

acetonitrile

反応条件

後処理

1. 1
   ろ過The reaction mixture was filtered
2. 2
   その他to remove the bulk of the DCU
3. 3
   その他the filtrate was evaporated in vacuo to dryness
4. 4
   workup.DISSOLUTIONThe resulting semi-solid residue was redissolved in THF
5. 5
   ろ過the mixture filtered
6. 6
   その他to remove any residual DCU
7. 7
   その他The filtrate was evaporated in vacuo
8. 8
   その他to give crude N-benzoyl-L-leucine N-hydroxysuccinimide ester as a foamy residue
9. 9
   workup.WAITto proceed at room temperature for 24 hours
10. 10
    濃縮The reaction mixture was then concentrated in vacuo to half its original volume
11. 11
    ろ過filtered
12. 12
    抽出The filtrate (pH 9) was extracted with ethyl acetate (2×50 ml)
13. 13
    その他The aqueous layer was separated
14. 14
    抽出extracted with methylene chloride (3×50 ml)
15. 15
    抽出The methylene chloride extract
16. 16
    乾燥was dried over anhydrous sodium sulfate
17. 17
    ろ過filtered
18. 18
    その他The filtrate was evaporated in vacuo
19. 19
    その他to give 2.80 g (92.4% yield) of crude product as a tacky white solid
20. 20
    その他This was triturated with diethyl ether
21. 21
    その他collected
22. 22
    その他to give 1.30 g (42.9% yield of white powdery 11, mp 136°-137° C. [α]D23 +0.7°(c 1.0, CH3OH)
23. 23
    その他quenching

実験手順

DCC (2.41 g, 0.0117 mol) and N-hydroxysuccinimide (1.35 g, 0.0117 mol) were added to a solution of N-benzoyl-L-leucine (2.75 g, 0.0117 mol) in 100 ml of acetonitrile at ice bath temperature. The reaction was allowed to proceed at this temperature for 2 hours. The reaction mixture was filtered to remove the bulk of the DCU and the filtrate was evaporated in vacuo to dryness. The resulting semi-solid residue was redissolved in THF and the mixture filtered to remove any residual DCU. The filtrate was evaporated in vacuo to give crude N-benzoyl-L-leucine N-hydroxysuccinimide ester as a foamy residue. IR (neat, cm-1) 3340 NH), 3060 (C6H5), 1820, 1790, 1740 and 1650 (C=O); NMR (Silanor C, δ from TMS) 7.3-7.9 (m, C6H5), 5.1-5.3 (m, --NH--CH--C=O), 2.8 (s, cycl. --CH2 --CH2 --), 1.6-2.2 (m, CH--CH2 --), 0.9-1.1 (d, (CH3)3CH). This was dissolved in 100 ml of THF and added drop-wise to a solution of sodium cyanamide (1.50 g, 0.0234 mol) in 100 ml of distilled water at ice bath temperature. The reaction was allowed to proceed at room temperature for 24 hours. The reaction mixture was then concentrated in vacuo to half its original volume and filtered. The filtrate (pH 9) was extracted with ethyl acetate (2×50 ml). The aqueous layer was separated, acidified to pH 1.5 with 10% HCl, and extracted with methylene chloride (3×50 ml). The methylene chloride extract was dried over anhydrous sodium sulfate and filtered. The filtrate was evaporated in vacuo to give 2.80 g (92.4% yield) of crude product as a tacky white solid. This was triturated with diethyl ether and collected to give 1.30 g (42.9% yield of white powdery 11, mp 136°-137° C. [α]D23 +0.7°(c 1.0, CH3OH); TLC: Rf =0.93 in EtOAc/petroleum ether/THF/CH2Cl2 / AcOH (50:50:10:50:4) and 0.24 in EtOAc/petroleum ether/AcOH (50:100:1), detected by UV quenching and orange color with ferricyanide spray reagent; IR (Nujol, cm-1) 3300, 3100 (NH), 2230 (C≡N), 1750 and 1630 (C=O); NMR (Silanor-DMSO, δ from TMS) 7.4-8.0 (d, C6H5 --), 4.2-4.6 (m, --NH--CH--C=O), 1.4-1.9 (m, CH--CH2 --), 0.8-1.1 (d, (CH3)2CH--) Anal. Calcd for C14H17N3O2 : C, 64.85; H, 6.61; N, 16.20. Found C, 64.62; H, 6.73; N, 15.93.

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