Synthesis
In a 20 L three-necked flask, 1.070 Kg of potassium hydroxide (KOH) was dissolved in 10 L of distilled water and stirred until completely dissolved to form a clarified solution. Subsequently, 5 g of silica-functionalized magnetic nanoparticles (Fe3O4@SiO2) were added to the solution. Under continuous stirring, 2 Kg of guanidine carbonate was added to the above mixture to ensure its complete dissolution. The temperature of the reaction system was maintained at around 20°C. Over a period of 3 hours, 2.4 kg of diethyl ethoxymethyl malonate was slowly added dropwise while the reaction temperature was gradually increased from 20 °C to 35 °C. A yellow solid precipitated during the reaction and the reaction mixture was subsequently cooled. The Fe3O4@SiO2 particles were separated and removed using an external magnet and the particles were washed with acetone and dried. The reaction mixture was further cooled to 0-5°C and filtered to obtain a light yellow consistency, which was washed well with ice water. The crude product was recrystallized by ethanol/water solvent mixture and dried in an oven at 40°C. The dried product was divided into two parts and dissolved in 15 L of 60% water/40% ethanol mixed solvent for secondary recrystallization. The initial recrystallized solution was turbid and was clarified by steam heating for 1 hour. Subsequently, the solution began to crystallize at 39°C and was slowly cooled to room temperature. The above recrystallization process was repeated for both parts of the product and the final product was dried in a vacuum oven. Yield: 95%.
References
[1] Asian Journal of Chemistry, 2017, vol. 29, # 10, p. 2119 - 2122
[2] Bioorganic and Medicinal Chemistry, 2007, vol. 15, # 14, p. 4841 - 4856
[3] Patent: US6194419, 2001, B1
