Sodium Hydroxide → 5-Bromo-2-methoxypyridine

Participants

Reaction Conditions

Reaction Steps

Ethyl acetate (325 kg), sodium acetate (58 kg, 707 mol) and 2-methoxypyridine (68.7 kg, 630 mol) were mixed in a reactor vessel (inner volume 1000 L). To this solution was added dropwise bromine (122.3 kg, 765 mol) over 6.5 hr while keeping the inside temperature from exceeding 10° C. After the dropwise addition, the inside temperature was raised to 20° C. and the mixture was stirred for 5 hr. The ratio of reaction progress at this time point was 73%. Thereafter, the inside temperature was raised to 50° C. and the reaction was continued more for 5 hr. The ratio of reaction progress at this time point was 98%. The reaction mixture was cooled and water (70 kg) was added to the reaction mixture. While keeping the inside temperature from exceeding 5° C., the solution obtained by dissolving sodium hydroxide (46.1 kg) and sodium sulfite (17 kg) in water (200 kg) was added dropwise. The reaction mixture was stood still to allow partitioning. After confirming that the pH of the aqueous layer was not less than 8 and peroxide was absent, the organic layer was separated. The aqueous layer was extracted with ethyl acetate (40 kg), and the extract and the above-mentioned organic layers were combined. The mixture was concentrated under reduced pressure to give crude 5-bromo-2-methoxypyridine (gross: 121.8 kg, net: 110.7 kg, yield 93%). The crude product was purified by distillation under reduced pressure to give 5-bromo-2-methoxypyridine (101.8 kg, yield 86%) having the following analytical data at a purity of not less than 99%.

Provenance & Evidence