1,1'-Carbonyldiimidazole → Ethyl 3-(2-fluoro-5-iodophenyl)-3-oxopropanoate

Participants

Reaction Steps

Employing the method utilized by Wang (Wang, X., Monte, W. T., Napier, J. J., Ghannam, A. Tetrahedron. Lett. 1994, 35, 9323), 1,1′-carbonyldiimidazole (1.82 g) in THF (20 mL) at 0° C. is treated with 2-fluoro-5-iodobenzoic acid (2.66 g) prepared according to literature procedures (Blackburn, B. K., Lee, A., Baier, M., Kohl, B., Olivero, A. G., Matamoros, R., Robarge, K. D., McDowell, R. S. J. Med Chem. 1997, 40, 717-729.) in portions over a 10 minute period. The mixture is stirred for 1 h and then allowed to warm to room temperature for an additional 1 h. The solution is then added dropwise into an enolate solution of ethyl trimethylsilymalonate at 5° C. prepared by the addition of DBU (3.35 g) to a solution of ethyl trimethylsilylmalonate (2.25 g) in acetonitrile (20 mL) at 5° C. with stirring for 45 minutes. The reaction mixture is allowed to warm to room temperature and stirred overnight. The orange solution is quenched with 100 mL of aqueous 10% citric acid solution and extracted with ethyl acetate. The organic extract is washed with aqueous 10% sodium bicarbonate solution and water, dried (Na2SO4), and concentrated in vacuo to give 2.4 g of the title compound as a yellow liquid. Physical characteristics: tlc Rf=0.66 (silica gel G; 20% EtOAc/hexane, visualize with I2).

Provenance & Evidence