Diethyl Malonate → Propanedioic acid, 2-(1-ethoxyethylidene)-, 1,3-diethyl ester

Temperature

140 °C

A mixture of diethyl malonate (4.8 mL), triethyl orthoacetate (17 mL), acetic anhydride (0.11 mL) and zinc chloride (1.2 g) was stirred at 140° C. To the mixture was added acetic anhydride (0.11 mL) each after 30, 90 and 120 minutes, and then stirred at the same temperature overnight. The reaction mixture was cooled to room temperature, and the insoluble material was removed by filtration. The filtrate was concentrated under reduced pressure, and the residue was purified by column chromatography on silica gel (eluent: n-hexane/ethyl acetate=4/1−7/3) to give diethyl 2-(1-ethoxyethylidene)malonate (5.02 g). To a solution of diethyl 2-(1-ethoxyethylidene)malonate (4.13 g) in ethanol (15 mL) were added formamidine hydrochloride (1.73 g) and a solution of potassium hydroxide (2.21 g) in water (7.5 mL), and the mixture was stirred at room temperature for 2 days. The reaction mixture was neutralized by adding acetic acid. To the mixture was added ethyl acetate (30 mL), and the mixture was stirred at room temperature for 30 minutes. The insoluble material was removed by filtration, and the filtrate was concentrated under reduced pressure. The residue was purified by column chromatography on silica gel (eluent: ethyl acetate−ethyl acetate/methanol=9/1) to give the title compound (1.5 g).

1. stirringstirred at the same temperature overnight
2. temperatureThe reaction mixture was cooled to room temperature
3. customthe insoluble material was removed by filtration
4. concentrationThe filtrate was concentrated under reduced pressure
5. customthe residue was purified by column chromatography on silica gel (eluent: n-hexane/ethyl acetate=4/1−7/3)

ORD record

ord-0a4b868e0847400fb50bb60203e360cb

Source dataset

uspto-grants-2012_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08217069B2