Citric Acid → Ethyl 3-[1-benzyloxy-3-(isoamyloxycarbonyl)cyclobutan-3-yl]-3-oxopropionate

Participants

Reaction Steps

A 21.49 g (67.08 mmol) portion of 1-benzyloxy-3-(isoamyloxycarbonyl)cyclobutane-3-carboxylic acid was dissolved in 200 ml of tetrahydrofuran to which, while cooling in an ice bath with stirring, was added 13.05 g (80.49 mmol) of N,N-carbonyldiimidazole. After 10 minutes of 2stirring, the ice bath was detached and the reaction mixture was stirred at room temperature for 3 hours. To the reaction solution which was cooled in an ice bath and stirred was added dropwise 100 ml of tetrahydrofuran solution containing 23.06 g (80.49 mmol) of magnesium ethylmalonate. After 1 hour of stirring, the ice bath was detached, and the reaction mixture was stirred at room temperature for 10 hours. While cooling in an ice bath and stirring, the reaction mixture was mixed with 10% citric acid aqueous solution and then with ethyl acetate to effect separation of layers, and the resulting organic layer was washed with saturated sodium bicarbonate aqueous solution and saturated brine. The organic layer was dried over anhydrous sodium sulfate and filtered, the solvent was evaporated under a reduced pressure and then the resulting residue was purified by a silica gel column chromatography (n-hexane:ethyl acetate=2:1) to give 11.37 g (29.12 mmol) of the title compound.

Provenance & Evidence