Synthesis
General procedure for the synthesis of monoethyl 2,2-dimethylmalonate from diethyl 2,2-dimethylmalonate: potassium hydroxide (7.5 g, 131.5 mmol) was added to a solution of diethyl 2,2-dimethylmalonate (25.0 g, 132.8 mmol) in ethanol (100.0 mL). The reaction mixture was stirred at room temperature for 12 hours. Upon completion of the reaction, the solvent was removed by distillation under reduced pressure. The residue was dissolved in water and extracted with ether. The aqueous phase was acidified to pH 4 with aqueous 6N hydrochloric acid and subsequently extracted with ethyl acetate. The ethyl acetate extracts were combined, washed sequentially with water and saturated saline, and dried over anhydrous sodium sulfate. After filtration, the filtrate was concentrated under reduced pressure to give 17.0 g of monoethyl 2,2-dimethylmalonate as an orange liquid. Yield: 80%; MS data: m/z 161 [M + H]+.
References
[1] Patent: WO2007/20936, 2007, A1. Location in patent: Page/Page column 114-115
[2] Patent: US2011/71196, 2011, A1. Location in patent: Page/Page column 31
[3] Journal of Medicinal Chemistry, 2009, vol. 52, # 21, p. 6790 - 6802
[4] Patent: WO2015/95227, 2015, A2. Location in patent: Page/Page column 101; 102
[5] Helvetica Chimica Acta, 1935, vol. 18, p. 1279
