Hydrochloric Acid → HCID 21838162, compound

Participants

Reaction Conditions

Reaction Steps

Ethyl glycolate (50.4 g) was added dropwise to a stirred suspension of sodium hydride (60% oil suspension, 38.7 g) in N,N-dimethylformamide (770 ml) for 8 minutes at 5-10° C. under nitrogen gas, and the mixture was stirred for 30 minutes at the same temperature. To the mixture was added dropwise over 10 minutes a solution of 6-fluoro-2-iodobenzaldehyde (110 g) in N,N-dimethylformamide (110 ml) at ambient temperature, and the mixture was stirred for 1.5 hours at 90-95° C. After cooling to 25° C., the reaction mixture was added 2N-sodium hydroxide (220 ml) and stirred for 1 hour at ambient temperature. The mixture was poured onto the mixture of water and ethyl acetate and the separated aqueous layer was adjusted to pH 2 with 6N-hydrochloric acid. The mixture was extracted with ethyl acetate and the extract layer was washed with brine, dried over magnesium sulfate and evaporated in vacuo to give 2-carboxy-4-iodobenzofuran. The mixture of the above residue and conc. sulfuric acid (20 ml) in methanol (200 ml) was heated under reflux for 16 hours. After evaporation of the solvent, the residue was added to water and the mixture was adjusted to pH 8 with potassium carbonate. The mixture was extracted with ethyl acetate and the extract layer was washed with brine, dried over magnesium sulfate and evaporated in vacuo. The residue was triturated with diisopropyl ether to give methyl 4-iodobenzofuran-2-carboxylate (16.13 g).

Provenance & Evidence