Methyl iodide → 6-Bromo-3-methoxy-2-methylpyridine

A mixture of 6-bromo-2-methyl-pyridin-3-ol (4.06 g, 21.59 mmol), methyl iodide (1.61 mL, 25.91 mmol), potassium carbonate (5.97 g, 43.18 mmol) and acetonitrile (183.0 mL) was heated at reflux for 17 hours. The mixture was cooled to room temperature, filtered through a plug of celite and the solvent was evaporated under reduced pressure. Water (50 mL) and ethyl acetate (100 mL) were added. The layers were separated and the aqueous layer was extracted with ethyl acetate (2×50 mL). The combined organic layers were dried over sodium sulfate, filtered and the solvent was evaporated under reduced pressure. The crude product was purified by silica gel chromatography utilizing a gradient of 0-20% ethyl acetate in hexane to yield 6-bromo-3-methoxy-2-methyl-pyridine (3.18 g, 73%) as a white solid. 1H NMR (400 MHz, DMSO) δ 7.42 (d, J=8.6 Hz, 1H), 7.33 (d, J=8.6 Hz, 1H), 3.82 (s, 3H), 2.32 (s, 3H). ESI-MS m/z calc. 201.0, found 202.1 (M+1)+; Retention time: 1.19 minutes (3 min run).

1. temperaturewas heated
2. temperatureat reflux for 17 hours
3. filtrationfiltered through a plug of celite
4. customthe solvent was evaporated under reduced pressure
5. additionWater (50 mL) and ethyl acetate (100 mL) were added
6. customThe layers were separated
7. extractionthe aqueous layer was extracted with ethyl acetate (2×50 mL)
8. dry with materialThe combined organic layers were dried over sodium sulfate
9. filtrationfiltered
10. customthe solvent was evaporated under reduced pressure
11. customThe crude product was purified by silica gel chromatography

ORD record

ord-e5362d65c9224dc6bd91f50a81cc21f4

Source dataset

uspto-grants-2016_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09365588B2