(2-(2-Aminoethoxy)ethoxy)acetic acid

DescriptionAmino-PEG2-CH2CO2H is a PEG compound containing an amino group with a terminal carboxylic acid. The amine group is reactive with carboxylic acids, activated NHS esters, carbonyls (ketone, aldehyde) etc. The terminal carboxylic acid can react with primary amine groups in the presence of activators (e.g. EDC, or HATU) to form a stable amide bond.

Uses[2-(2-Aminoethoxy)ethoxy]acetic Acid is used in the development of chemically modified peptide nucleic acid (PNA) as a probe for qualitative and quantitative detection of DNA. It is also used in the preparation and studies of the biological activities of kappa agonist CovX-bodies.

PreparationIn a 2L three-necked flask equipped with a mechanical stirrer and a constant-pressure dropping funnel, diethylene glycolamine (100g, 1.0eq) and tetrahydrofuran (500mL, 5.0v/w) were added sequentially, and the temperature was lowered to 0–5℃. Then, 500mL of a tetrahydrofuran-diluted Boc₂O solution (207.58g, 1.0eq) was added dropwise. The temperature was raised to 10–20℃ and the reaction was carried out for 10 hours. IPC analysis indicated the reaction was complete. After cooling to 0–5℃, sodium tert-butoxide (91.40g, 1.0eq) was added in portions. After the addition was complete, the mixture was kept at this temperature and stirred for 1 hour. Then, sodium chloroacetate (143.46g, 1.3eq) was added dropwise. After the addition was complete, the temperature was raised to 10–20℃ and the reaction was carried out for 5 hours. IPC analysis indicated the reaction was complete. The reaction was completed by pH testing; the mixture was concentrated under reduced pressure at 40–45 °C to remove tetrahydrofuran; concentrated hydrochloric acid (475.56 g, 5.0 eq) was added, and the mixture was stirred at 10–20 °C for 3 hours. The reaction was then completed by IPC testing. The pH was adjusted to 6–7 with 40% NaOH solution, and the mixture was extracted with a large amount of tetrahydrofuran. The organic phase was evaporated to dryness and then distilled with ethanol to remove water. The mixture was recrystallized with 300 mL of ethanol; the mixture was filtered, and the filter cake was dried under vacuum at 35 °C to obtain 95.1 g of 2-(2-(2-aminoethoxy)ethoxy)acetic acid, with a total yield of 61.3%.