Sodium Hydroxide → 3-((2-Fluoro-4-iodophenyl)amino)isonicotinic acid

Participants

Reaction Conditions

Reaction Steps

A mixture of 2-fluoro-4-iodo-phenylamine (20.0 g, 84.38 mmol) in anhydrous tetrahydrofuran (80 mL) was cooled to −65° C. under an inert atmosphere, prior to slow addition of 1.0 M lithium bis(trimethylsilyl)amide (255 mL, 255 mmol) at a rate that maintained the internal temperature below −55° C. After final addition, the thick slurry was stirred for 30 minutes and then treated with 3-fluoro-isonicotinic acid (8.0 g, 56.69 mmol). The mixture was stirred at room temperature for 4 days and then poured into aqueous 2.0 N sodium hydroxide (1000 mL) and ethyl acetate (250 mL). The layers were separated and the organics were again extracted with aqueous sodium hydroxide (2×1000 mL). The pH of the combined aqueous fractions was adjusted to 2 with concentrated hydrochloric acid, which effected precipitation of a solid. The material was filtered, washed with water (300 mL) and dried under high vacuum at 40° C. for 18 h to afford the product (19.05 g, 53.19 mmol, 94%) as a yellow solid.

Provenance & Evidence