Hydrochloric Acid → Methyl 6-(2-fluoro-5-methoxyphenyl)-5-isobutoxy-2-methoxynicotinate

Participants

Reaction Conditions

Reaction Steps

Under a nitrogen atmosphere, to a solution of methyl 2-chloro-6-(2-fluoro-5-methoxyphenyl)-5-isobutoxynicotinate (248 mg) in THF (5.0 mL) was added a 28% solution of sodium methoxide in methanol (3.42 mL). The reaction mixture was stirred at room temperature for 1 hr and further at 60° C. for 48 hr. 6N Hydrochloric acid (0.44 mL) was added to the reaction mixture, and the resulting sodium chloride was filtered off. The solvent in the filtrate was evaporated under reduced pressure, and the residue was heated with conc. sulfuric acid (108 μL) and methanol (10 mL) under reflux for 3 hr. The reaction mixture was neutralized with sodium hydrogen carbonate, and the solvent in the reaction mixture was evaporated under reduced pressure and the residue was filtered. The solvent in the filtrate was evaporated under reduced pressure to give a crude product of the title compound (213 mg) as a yellow oil. This compound was used for the next step without further purification.

Provenance & Evidence