Trifluoroacetic anhydride → (3-Bromo-6-chloro-4-methylpyridin-2-yl)methanol

Participants

Reaction Steps

To a solution of 3-bromo-6-chloro-2,4-dimethylpyridine 1-oxide (28.7 g, 121 mmol) in CH2Cl2 (240 mL) was added trifluoracetic anhydride (240 mL, 1699 mmol). The reaction was stirred for 3 hours at room temperature and then concentrated. The residue was dissolved in MeOH (1.7 L) and cooled to 0° C. 1M K2CO3 (360 mL, 360 mmol) was added dropwise, and the reaction was stirred for 10 minutes at 0° C. and then warmed to r.t. for 1 hour. The reaction was then concentrated to a volume of 300 mL and diluted with EtOAc (1 L). Water (1 L) was added and the layers were separated. The aqueous layer was extracted with additional EtOAc (2×1 L). The organic layers were combined, washed with brine (1 L), dried over Na2SO4, filtered, and concentrated. Purification of the residue by flash chromatography on silica gel with 0 to 75% EtOAc/heptanes afforded (3-bromo-6-chloro-4-methylpyridin-2-yl)methanol. LCMS=236.1 and 238.1 (M+H)+ 1H NMR (CDCl3, 500 MHz) δ 7.17 (s, 1H), 4.73 (s, 2H), 2.42 (s, 3H).

Provenance & Evidence