5-Bromo-2-methoxy-4-methylpyridine

Sodium acetate (3.54g. 43.23mmol) was added to a solution of 2-methoxy-4-methylpyridine (5.0g.3gmmol) in EtOAc (25mL). Br2 (1 .52mL, 58mmol) was added drop-wise to over 20 mm at 0°C. The RM was stirred at 50°C for 18 h. The total reaction mass was cooled, and after diluting it with water, the pH was adjusted to 8 with aq. NaOH. The organic layer was separated, and aq. Layer extracted with EtOAc (250mL x 3). The combined extract was washed with water (300 mL), brine (200 mL), dried (Na2SO4) and concentrated under reduced pressure to get a crude compound. The crude compound was purified by CC(silica gel 100-200mesh, 0-5 per cent EtOAc in PE) to obtain 5-bromo-2-methoxy-4-methylpyridine (2.82g. 40 per cent) as liquid.

[1] Patent: US2016/176882, 2016, A1. Location in patent: Paragraph 0355; 0356
[2] Patent: WO2017/221100, 2017, A1. Location in patent: Paragraph 00166