2-hydroxy-5-iodonicotinic acid synthesis

Yield:390360-97-1 91 %

Reaction Conditions:

with lithium hydroxide monohydrate;water in tetrahydrofuran at 50;

Steps:

27.1 6-chloro-5-(5,7-difluoro-4-oxo-1,4-dihydroquinolin-2-yl)nicotinonitrile

Step 1, 2-hydroxy-5-iodonicotinic acid: To a solution of methyl 2-chloro-5- iodonicotinate (3.0 g, 10.7 mmol, 1.0 equiv.) in THF (20 mL) and H2O (7 mL) was added LiOH·H₂O (1.3 g, 32.2 mmol, 3.0 equiv.). The mixture was stirred at 50 °C for 16 hours. The mixture was concentrated under reduced pressure to remove THF. The pH of the mixture was adjusted to pH = 6 with aqueous 1 M HCl. During the pH adjustment a white solid precipitated and was collected by filtration. The filter cake was washed with H₂O (10 mL) and concentrated in vacuum to give 2-hydroxy-5-iodonicotinic acid (2.5 g, 91% yield) as a white solid. LCMS [M+1] = 265.9.¹H NMR (400 MHz, DMSO-d6) δ 8.28 (d, J = 2.4 Hz, 1H), 8.21 (d, J = 2.4 Hz, 1H).

References:

WO2023/14861,2023,A1 Location in patent:Paragraph 00115-00117