Bromine → 4-Bromo-3,5-dimethoxypyridine

To a stirred solution of 3,5-dimethoxypyridine (2.7 g, 19.4 mmol) in dry THF at −78° C. was added n-butyllithium (23.3 mmol, 2 M solution in cyclohexanes). During this addition a precipitate formed and the reaction was allowed to warm to room temperature for 5 minutes. The precipitate separated into an oily phase and the reaction was re-cooled and treated with bromine (1.5 ml, 29.1 mmol) and again allowed to warm to room temperature. After stirring for 10 minutes the solution became homogeneous and was quenched with 10% Na2S2O3 (aq) and extracted with EtOAc. The organic layer was washed with brine, dried over MgSO4 and concentrated onto silica-gel under reduced pressure. The solid residue was purified by flash chromatography (silica-gel, eluted sequentially with hexanes:EtOAc, 2:1, 1:1, 1:2) to give the product as a white solid (2.4 g, 57%). 1H-NMR (300 MHz, CDCl3) δ 7.95 (s, 2H), 3.99 (s, 6H).

1. additionDuring this addition a precipitate
2. customformed
3. customThe precipitate separated into an oily phase
4. temperaturethe reaction was re-cooled
5. temperatureto warm to room temperature
6. customwas quenched with 10% Na2S2O3 (aq)
7. extractionextracted with EtOAc
8. washThe organic layer was washed with brine
9. dry with materialdried over MgSO4
10. concentrationconcentrated onto silica-gel under reduced pressure
11. customThe solid residue was purified by flash chromatography (silica-gel
12. washeluted sequentially with hexanes

ORD record

ord-06e3ced1aab04d90b4030456a51ec406

Source dataset

uspto-grants-2013_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08466163B2