2-Pyridinecarboxylic acid, 5-bromo-6-fluoro-, methyl ester synthesis

Yield:1214336-44-3 90%

Reaction Conditions:

with silver(II) fluoride in acetonitrile at 20;

Steps:

7 Intermediate 20: methyl 5-bromo-6-fluoro-oyridine-2-carboxylate

An oven dried flask was charged with methyl 5-bromopyridine-2-carboxylate (Intermediate 19, 6 g, 27.77 mmol) in acetonitrile (60 mL). Silver (II) fluoride (14.18 g, 97.21 mmol) was added and the mixture was stirred at room temperature for overnight. Reaction mixture was filtered through filter paper and washed with DCM. The filtrate was concentrated to give a light brown solid. The residue was suspended in a mixture of DCM and sat. NhUCI solution and the white suspension was filtered off. The organic layer was separated, and the aqueous layer was extracted with DCM (100 ml x 2). The combined organic layers were dried over Na2SC>4, filtered and concentrated. The resulting residue was purified by flash silica chromatography, elution gradient 0 to 25% EtOAc in hexanes. Product fractions were concentrated under reduced pressure to dryness to afford methyl 5-bromo-6-fluoro-pyridine-2- carboxylate (Intermediate 20, 5.98g yield 90%). ¹H NMR (500 MHz, CHLOROFORM-d) 4.01 (3H, s), 7.93 (1 H, d), 8.15 (1 H, t); m/z (ES⁺) [M]⁺ = 234.

References:

WO2021/13735,2021,A1 Location in patent:Page/Page column 19