The general procedure for the synthesis of tert-butyl 5-bromopyridine-2-carboxylate from 2-carboxylic acid-5-bromopyridine and tert-butanol was as follows: 2-carboxylic acid-5-bromopyridine (118 mg, 0.58 mmol) was mixed with pyridine (0.3 mL, 0.39 mmol) and tert-butanol (1 mL), and p-toluenesulfonyl chloride (262 mg, 1.38 mmol) was subsequently added. The reaction mixture was stirred at 40°C for 10 minutes and then continued to stir at room temperature for 2 hours. After the reaction was completed, saturated sodium bicarbonate solution (4 mL) was added and stirred for 5 minutes. Then diethyl ether was added and the two-phase mixture was stirred for 10 minutes. The organic layer was separated, washed with brine, dried with anhydrous magnesium sulfate and subsequently concentrated under reduced pressure. The residue was purified by silica gel column chromatography with the eluent being pentane: ethyl acetate (100:0 to 80:20) to afford tert-butyl 5-bromopyridine-2-carboxylate as a colorless solid in 73% (110 mg) yield. The product was confirmed by 1H-NMR (CDCl3, 400 MHz): δ 1.65 (s, 9H), 7.95 (m, 2H), 8.88 (m, 1H). The mass spectrum (ES+) showed m/z 539 [M2Na]+.
