반응 #83135

반응 방정식

triethylamine

2-pyrazineethaneamine hydrochloride

2-adamantyloxycarbonyl-α-methyl-DL-tryptophan

1-hydroxybenzotriazole hydrate

1,3-dicyclohexylcarbodiimide

→

desired product

수율 63.2%

Tricyclo[3.3.1.13,7 ]dec-2-yl (±)-[1-(1H-indol-3-ylmethyl)-1-methyl-2-oxo-2-[[2-(2-pyrazinyl)ethyl]amino]ethyl]carbamate

수율 63.2%

용매

water

ethyl acetate

반응 조건

후처리

1. 1
   기타The reaction
2. 2
   workup.STIRRINGas stirred for 1.75 hours
3. 3
   여과filtered
4. 4
   세척The filtrate was washed with aqueous 1M citric acid (2×15 mL), saturated aqueous NaHCO3 (2×15 mL), and saturated aqueous NaCl (15 mL)
5. 5
   건조dried over Na2SO4
6. 6
   농축concentrated in vacuo
7. 7
   workup.ADDITIONThe residue was treated with 1,2-dimethoxyethane (5 mL)
8. 8
   workup.WAITto stand at 0°-5° C. for 16 hours
9. 9
   여과filtered
10. 10
    농축concentrated in vacuo
11. 11
    기타Chromatography (flash, SiO2, 230-400 mesh, 0.5% triethylamine/10% isopropanol/ethyl acetate eluant, 15×2.5 cm) gave a clear oil
12. 12
    기타upon solvent removal
13. 13
    workup.DISSOLUTIONThe residue was dissolved in methanol (10 mL)
14. 14
    농축water (1 mL) and concentrated in vacuo until a solid
15. 15
    기타formed
16. 16
    여과filtered
17. 17
    기타dried

실험 절차

A room temperature solution of 0.40 g (1.01 mmol) of 2-adamantyloxycarbonyl-α-methyl-DL-tryptophan and 0.15 g (1.11 mmol) of 1-hydroxybenzotriazole hydrate in 15 mL of anhydrous ethyl acetate under N2 atmosphere was treated with 0.23 g (1.11 mmol) of 1,3-dicyclohexylcarbodiimide in one portion. The reaction was stirred for 1.75 hours and treated with 0.12 g (1.22 mmol) of triethylamine and 0.17 g (1.07 mmol) of 2-pyrazineethaneamine hydrochloride. The reaction as stirred for 1.75 hours and filtered. The filtrate was washed with aqueous 1M citric acid (2×15 mL), saturated aqueous NaHCO3 (2×15 mL), and saturated aqueous NaCl (15 mL), dried over Na2SO4, and concentrated in vacuo. The residue was treated with 1,2-dimethoxyethane (5 mL), allowed to stand at 0°-5° C. for 16 hours, filtered, and concentrated in vacuo. Chromatography (flash, SiO2, 230-400 mesh, 0.5% triethylamine/10% isopropanol/ethyl acetate eluant, 15×2.5 cm) gave a clear oil upon solvent removal. The residue was dissolved in methanol (10 mL) and water (1 mL) and concentrated in vacuo until a solid formed. The solid was suspended in water, filtered, and dried to give 0.32 g (63%) of the desired product as a white solid; mp 97°-101° C.; 1H NMR (CDCl3) δ1.4-2.0 (17H, m), 2.87 (2H, m), 3.29 (1H, d, J 15 Hz), 3.46 (1H, d, J 15 Hz), 3.62 (2H, m), 4.74 (1H, br s), 5.23 (1H, br s), 6.95 (2H, br s), 7.0-7.2 (2H, m), 7.33 (1H, d, J 8 Hz), 7.58 (1H, d, J 8 Hz), 8.20 (1H, br s), 8.37 (2H, s), 8.38 (1H, s).

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