Bromine → 5-Bromo-2-methoxypyridine

To a suspension of 2-methoxypyridine (1-1) (3.96 kg; 36.3 mol), NaOAc (3.57 kg; 39.9 mol), and dichloromethane (22 L) was added a solution of bromine (2.06 L; 39.9 mol) in dichloromethane (2 L), maintaining the reaction temperature below 7° C. over 2-3 hours. The mixture was aged for 1 hour at 0-7° C. and stirred at room temperature overnight. The reaction mixture was filtered and rinsed with dichloromethane (about 5 L). The filtrate and washings were combined, washed with cold 2 M NaOH (22 L; pH should be below 8) maintaining the temperature below 10° C., and with cold water (11 L). The organic layer was separated and concentrated under reduced pressure to give a crude product 1-2 (6.65 kg). The crude product was purified by vacuum distillation to give pure 1-2 (5.90 kg, 86%). Known compound: G. Butora et al., JACS, 119, 7694-7701 (1997).

1. temperaturemaintaining the reaction temperature below 7° C. over 2-3 hours
2. filtrationThe reaction mixture was filtered
3. washrinsed with dichloromethane (about 5 L)
4. washwashed with cold 2 M NaOH (22 L; pH should be below 8)
5. temperaturemaintaining the temperature below 10° C.
6. customThe organic layer was separated
7. concentrationconcentrated under reduced pressure
8. customto give a crude product 1-2 (6.65 kg)
9. distillationThe crude product was purified by vacuum distillation

ORD record

ord-533500df325447799f03ca0b5234b7ad

Source dataset

uspto-grants-2002_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06472403B2