Preparation of 2-[2-(2-azidoethoxy)ethoxy]ethylamine

2-[2-(2-azidoethoxy)ethoxy]ethanamine is used as a pharmaceutical synthesis intermediate. If 2-[2-(2-azidoethoxy)ethoxy]ethanamine is inhaled, remove the patient to fresh air; in case of skin contact, remove contaminated clothing, rinse skin thoroughly with soapy water and water, and seek medical attention if you feel unwell.

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.