Malonate Ion → Cyclopropanepropanoic acid, 2,2-difluoro-beta-oxo-, ethyl ester

Participants

Reaction Conditions

Reaction Steps

To monoethyl malonate (2.164 g, 16.4 mmol) in a round bottom flask under inert argon atmosphere was added 60 ml of THF and the vessel was cooled to −78° C. To this was added n-butyllithium solution (20.48 ml of 1.6 M in hexane, 32.8 mmol) and the temperature was raised gradually until it reached 0° C. for 15 minutes. The lithiated malonate solution was then cooled to −78° C. again and the crude 2,2-difluoro-cyclopropanecarbonyl chloride dissolved in THF (10 mL) was added drop wise over 20 minutes and the reaction mixture was warmed to 0° C. at which time the reaction was complete as shown by TLC (potasiumpermanganate stain). The reaction mixture was then worked up with (2×20 ml) saturated sodium hydrogen carbonate solution and (1×20 ml) saturated brine solution. This was then extracted with (2×20 ml) ethyl acetate and the organic portion of the reaction mixture was then reduced in-vacuo and subsequently adsorbed onto silica and chromatographed (AcOEt 10:90 heptane). Combination of the desired fractions and evaporation afforded 3-(2,2-difluoro-cyclopropyl)-3-oxo-propionic acid ethyl ester (678 mg, 43% yield) as a colourless liquid. MS (ESI+): 193.3, 4 ([M+H]+).

Provenance & Evidence