2-Bromonicotinic acid

Chemical Properties

Synthesis

3430-17-9

35905-85-2

General procedure for the synthesis of 2-bromonicotinic acid from 2-bromo-3-methylpyridine: 2-bromo-3-methylpyridine (25.0 mL, 213 mmol) was slowly added to a solution of potassium permanganate (87.7 g, 555 mmol) dissolved in 800 mL of water, and the mixture was stirred continuously for 5 hours under reflux conditions. Upon completion of the reaction, 600 mL of water was removed by distillation and the remaining suspension was separated by thermal filtration. The filtrate was washed with two portions of 50 mL of hot water, and the combined filtrates were acidified with concentrated hydrochloric acid to pH < 2. The precipitate was collected by filtration and dried in a vacuum drying oven to give 26.8 g of 2-bromonicotinic acid in 62% yield. Diphenylphosphoryl chloride was added dropwise to a solution of 2-bromonicotinic acid (15.0 g, 74.0 mmol) and triethylamine (11.4 mL, 81.4 mmol) dissolved in 140 mL of anhydrous tert-butanol. The reaction mixture was stirred under reflux conditions for 2 h. It was cooled to room temperature and concentrated under reduced pressure. The residue was dissolved in 150 mL of ethyl acetate and washed sequentially with three parts of 50 mL of water, three parts of 50 mL of saturated aqueous sodium bicarbonate solution and two parts of 50 mL of saturated saline. The organic phase was dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. After static crystallization 15.3 g of the target product was obtained in 76% yield.

References