Diethyl Oxalate → (5-Fluorobenzofur-7-yl)oxoacetic acid ethyl ester

Participants

Reaction Steps

A mixture of 1.01 gm (4.72 mMol) 5-fluoro-7-bromobenzofuran, 0.15 gm (6.14 mMol) magnesium(0), and 2 drops of 1,2-dibromoethane in 1 mL diethyl ether was stirred at room temperature until initiation of the Grignard formation had occurred (about 5–10 minutes). The mixture was then diluted with 8 mL of diethyl ether and heated at reflux for 30 minutes. This mixture was then added dropwise to a solution of 1.38 gm (9.44 mMol) diethyl oxalate in 3 mL tetrahydrofuran at −10° C. Once the addition was complete the reaction mixture was allowed to warm to room temperature and was then stirred at room temperature for 30 minutes. The reaction mixture was diluted with 20 volumes of ethyl acetate and was washed sequentially with 1N hydrochloric acid, water, and saturated aqueous sodium chloride. The remaining organics were concentrated under reduced pressure. The residue was subjected to flash silica gel chromatography, eluting with hexane containing 30% ethyl acetate. Fractions containing the desired product were combined and concentrated under reduced pressure to provide 0.894 gm (80%) of the desired compound.

Provenance & Evidence