Ethyl diazoacetate → 2-(4-fluoro-phenyl)-cyclopropanecarboxylic Acid Ethyl Ester

Participants

Reaction Steps

In an oven-dried two-neck round flask equipped with condenser and Argon inlet was charged with 40 mL of newly opened anhydrous chloroform. Dry Argon gas was bubbled through the chloroform. copper (I) iodide (38 mg, 1 mol %) and palladium (II) acetate (45 mg, 1 mol %) were added to the Chloroform and stirred at room temperature for 15 minutes under argon. Then 4-fluorostyrene (2.4 mL, 20 mmol) in 20 mL of dry chloroform was added to the above solution. Finally ethyl diazoacetate (8.3 mL, 80 mmol) in 10 mL of chloroform was added dropwise to the reaction mixture over 2 hour. The reaction mixture was heated at 80° C. for overnight. The reaction mixture was cooled down to room temperature and rotavaped to afford dark green oil. The residue was diluted with 200 mL of ethyl acetate and washed with saturated sodium bicarbonate aqueous solution (1×50 mL), water (1×50 mL) and brine (1×50 mL) respectively. The ethyl acetate layer was dried over Sodium sulfate and concentrated to give 5 gram of light brown oil as crude product, which was purified with flash chromatography (40 gram prepacked column by Isco, Inc., 230-400 mesh, eluants: 0-20% ethyl acetate in hexanes) to obtain 2.625 grams of the desired product as clear oil. The trans configuration of the structure was confirmed by NOE of 1H NMR, yield=62%.

Provenance & Evidence