Synthesis
Example 1: Scheme 4
Preparation of diethyl 2-ethoxy-malonate
A mixture of diethyl oxalate (39.23 ml, 1.12 eq.) and ethyl 2-ethoxyacetate (34.95 ml, 1 eq.) was added dropwise to a slurry of sodium ethanolate (18.64 g, 1.07 eq.) in toluene (100 ml) at 45-50 °C. After the dropwise addition was completed, the reaction mixture was heated to 70-80°C and maintained for 2 hours. After completion of the reaction, the mixture was cooled and poured into 70 ml of 14% hydrochloric acid solution. The resulting mixture was extracted with ethyl acetate (EA), the organic layers were combined and washed with brine, dried over anhydrous sodium sulfate and concentrated under reduced pressure to give 55.86 g (93.7% yield) of the target product diethyl 2-ethoxy-malonate.
