Chemical Properties
white to light yellow crystal powder
Uses
Ethyl acetimidate hydrochloride was used in preparation of amidinated carbonic anhydrase via chemical modification of human erythrocyte carbonic anhydrase. It was also used in synthesis of methyl 2-methyl-2-thiazoline-4-carboxylate hydrochloride.
Synthesis
2) Example 1-2: Preparation of ethyl acetimidate hydrochloride
1.6 kg of acetonitrile and 4.3 kg of ethanol were added to the reactor and the reactor was cooled to -10°C. 3.67 kg of acetyl chloride was slowly added under stirring and the reaction mixture was kept stirred at 0°C for 12 hours. After completion of the reaction, the solvent was removed by distillation under reduced pressure at 45°C. To the residue was added 11.8 kg of tert-butyl methyl ether and stirred at room temperature for 3 hours. The precipitated solid was collected by filtration and dried under vacuum at 40 °C to give 4.58 kg ethyl acetimidate hydrochloride (yield: 95%).
Product characterization data: 1H-NMR (400 MHz, DMSO-d6) δ: 11.7 (s, 2H), 4.26 (q, 2H), 2.38 (s, 3H), 1.36 (t, 3H).
Purification Methods
Recrystallise the hydrochloride by dissolving it in the minimum volume of super dry EtOH and adding dry Et2O or from dry Et2O. Dry it in a vacuum and store it in a vacuum desiccator with P2O5. Alternatively it could be crystallised from EtOH (containing a couple of drops of ethanolic HCl) and adding dry Et2O. Filter and dry it in a vacuum desiccator over H2SO4 and NaOH. [Pinner Chem Ber 16 1654 1883, Glickman & Cope J Am Chem Soc 67 1020 1945, Chaplin & Hunter J Chem Soc 1118 1937, McElvain & Schroeder J Am Chem Soc 71 40 1949, McElvain & Tate J Am Chem Soc 73 2233 1951, Methods Enzymol 25 585 1972, Beilstein 2 III 418.]
References
[1] Combinatorial Chemistry and High Throughput Screening, 2011, vol. 14, # 2, p. 132 - 137
[2] Patent: WO2015/5615, 2015, A1. Location in patent: Paragraph 142; 143; 144
[3] New Journal of Chemistry, 2018, vol. 42, # 16, p. 13367 - 13374
[4] Journal of Medicinal Chemistry, 2004, vol. 47, # 4, p. 915 - 927
[5] Chemische Berichte, 1985, vol. 118, # 8, p. 3089 - 3104
