The general procedure for the synthesis of 2-fluoro-4-iodonicotinic acid from 2-fluoro-4-iodopyridine-3-carboxaldehyde was as follows: to a stirred solution of 2-fluoro-4-iodopyridine-3-carboxaldehyde (10.0 g, 39.8 mmol) in a solvent mixture of tert-butanol (350 mL) and water (100 mL) at room temperature was added sequentially 2-methyl-2-butene (42.1 mL, 398 mmol) and sodium chlorite (18.0 g, 199 mmol). 398 mmol), sodium phosphate monohydrate (60.5 g, 438 mmol) and sodium chlorite (18.0 g, 199 mmol). The reaction mixture was stirred continuously for 75 minutes at room temperature. Upon completion of the reaction, the reaction mixture was diluted with dichloromethane and the pH was adjusted to about 2 by slow addition of 6 M aqueous hydrochloric acid. subsequently, the aqueous layer was extracted with dichloromethane. The organic phases were combined, dried with anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. Finally, the target product 2-fluoro-4-iodonicotinic acid (10.63 g, 39.8 mmol, 100% yield) was purified by medium pressure liquid chromatography (MPLC) using a gradient elution (100/0 to 80/20) of dichloromethane/methanol (containing 1% acetic acid). Mass spectrum (ESI positive ion mode) m/z: 268 ([M+H]+). exact mass calculated for C6H3FINO2 was 267.
