ChemicalBook CAS DataBase List 2-[2-(2-Azidoethoxy)ethoxy]ethanamine

2-[2-(2-Azidoethoxy)ethoxy]ethanamine synthesis

11synthesis methods

Product Name:2-[2-(2-Azidoethoxy)ethoxy]ethanamine
CAS Number:166388-57-4
Molecular formula:C6H14N4O2
Molecular Weight:174.2

2-[2-(2-Hydroxyethoxy)ethoxy]ethyl chloride (15 g, 88.9 mmol), NaI(4.06 g, 27.1 mmol), and NaN₃ (45.3 mg, 697 mmol) were dissolved in distilled water (90 mL), and the solution was stirred for 48 h at 50 °C. The reaction mixture extracted with ethyl acetate for three times. The organic layer was dried over Na₂SO₄ , and evaporated to collect 2-[2-(2-azidoethoxy)ethoxy]ethanol (14.0 g, 90.1%) as a yellow oil.To the solution 2-[2-(2-azidoethoxy)ethoxy]ethanol (8 g, 45.7 mmol) in THF (22.4 mL), 6 M NaOH(20.8 mL) and TsCl (13.1 g, 68.6 mmol) were added at 0 °C. The reaction mixture was stirred for 1 h at room temperature under nitrogen atmosphere. The solution was then extracted with diethyl ether four times, and the organic layer was washed with 1 M NaOH. After evaporation of the organic layer,2-[2-(2-azidoethoxy)ethoxy]ethyl tosylate (16.8 g, 98.6%) was obtained as a yellow oil.Finally, ammonia solution (28%, 14.8 mL, 365 mol) was added to the 2-[2-(2-azidoethoxy)ethoxy]-ethyl tosylate (8 g, 24.3 mmol) dissolved in THF (95.9 mL), and reaction mixture was stirred for 96 h at 40 °C. After the reaction, distilled water (50 mL) was added to the solution. The mixture was washed with diethyl ether and then extracted with dichloromethane. The organic layer was dried over NaSO₄ and evaporated to obtain 2-[2-(2-azidoethoxy)ethoxy]ethanamine (2.49 g, 58.8%) as a yellow oil.
synthesis of 2-[2-(2-Azidoethoxy)ethoxy]ethanamine

synthesis of 2-[2-(2-Azidoethoxy)ethoxy]ethanamine

929-59-9 Synthesis

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166388-57-4
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Yield:166388-57-4 78%

Reaction Conditions:

with sodium azide;copper(ll) sulfate pentahydrate;trifluoromethylsulfonic anhydride;potassium carbonate in methanol;dichloromethane;water at 20;

Steps:

2-(2-(2-Azidoethoxy-exthoxy)ethanamine (N₃-PEG-NH₂)
NaN₃ (3.44 g, 52.9 mmol) in H₂O (12.0 mL) was mixed with CH₂Cl₂ (10.0 mL) in an ice-water bath. Tf₂O (1.8 mL, 10.7 mmol) in CH₂Cl₂ (8.0 mL) was added drop wise to the solution for 1 hr at 0 ^oC.¹ The resulting mixture was stirred at the same temperature for an additional 4 hr, and the layers were separated. The aqueous layer was further extracted with CH₂Cl₂ (40 mL). The CH₂Cl₂layers were combined, washed with aqueous saturated Na₂CO₃ (30 mL) and used as is without further purification. 2,2'-(Ethylenedioxy) bis(ethylamine) (3.1 mL, 21.2 mmol) in MeOH (20 mL) was added to K₂CO₃ (1.70 g, 12.3 mmol) and CuSO₄5H₂O (cat. 14 mg) in H₂O (4 mL). The CH₂Cl₂extracts of the first reaction was added drop wise over a period of 5 hr, and the reaction mixture was stirred at rt for 36 hr. Then the layers were separated and the organic layer was dried over anhydrous Na₂SO₄. The solution was filtered and concentrated under vacuum. The residue was purified by silica gel flash chromatography (MeOH:CH₂Cl₂5:95) to afford the desired product as a light yellow oil (R_f = 0.24 in 1:4 MeOH:CH₂Cl₂). Yield: 1.44 g, 78%. ¹H NMR (400 MHz, CDCl₃, rt): δ(ppm) 2.94 (s, br, 2 H), 3.41 (t, J = 5.00 Hz, 2 H), 3.56 (t, J = 5.04 Hz, 2 H), 3.66 (m, 6 H), 3.89 (s, br, 2 H); ¹³C NMR (100.6 MHz, CDCl₃, rt): δ(ppm) 42.02, 51.63, 70.95, 71.17, 71.60, 72.65; ESI-LRMS: [M+H]⁺, 175.4 (100%).

References:

Li, Ying;Schaffer, Paul;Perrin, David M. [Bioorganic and Medicinal Chemistry Letters,2013,vol. 23,# 23,p. 6313 - 6316] Location in patent:supporting information

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