Uses
Ethyl potassium malonate (potassium ethyl malonate) may be used to generate (trimethylsilyl)ethyl malonate
in situ, which can be acylated to prepare a variety of β-ketoesters or alkylidene malonates.
Uses
Ethyl potassium malonate is used as a competitive inhibitor of the enzyme succinate dehydrogenase. It acts as a precursor to produce (trimethylsilyl)ethyl malonate, which is utilized to prepare beta-ketoesters by acylation. Further, it reacts with aryl nitriles to prepare beta-amino acrylates in the presence of zinc chloride and a catalytic amount of Hünig's base. In addition to this, it serves as an intermediate for the preparation of ethyl tert-butyl malonate.
Synthesis
Step 1: Add diethyl malonate (100g, 0.625mol) and anhydrous ethanol (400ml) to a 2 liter round bottom flask fitted with a magnetic stirrer. A solution of potassium hydroxide (35 g, 0.624 mol) in anhydrous ethanol (400 ml) was slowly added dropwise at room temperature. After the dropwise addition, the reaction mixture was continued to be stirred overnight. Subsequently, the reaction mixture was heated to reflux and then slowly cooled to room temperature. The first products were isolated by vacuum filtration through a large No. 2 sintered glass funnel and dried at room temperature for 1 hour. The filtrate was concentrated to about 500 ml and then cooled to room temperature to precipitate the second batch of crystals. Combining the two batches of product, the total yield was 97.7 g with 92% yield.
References
[1] Patent: WO2012/25861, 2012, A1. Location in patent: Page/Page column 20
[2] Bioorganic and Medicinal Chemistry, 2004, vol. 12, # 18, p. 4995 - 5010
[3] Angewandte Chemie - International Edition, 2011, vol. 50, # 19, p. 4470 - 4474
[4] Chemistry - A European Journal, 2003, vol. 9, # 17, p. 4222 - 4231
[5] Tetrahedron, 2012, vol. 68, # 9, p. 2113 - 2120
