Methyl iodide → 2-Bromo-5-chloro-3-methoxypyridine

To a stirred mixture of 2-bromo-5-chloro-3-pyridinol (15.66 g) and pulverized KOH (16.79 g) in DMSO (100 mL) at 55-60° C. was added dropwise a solution of CH3I (13.27 g) in DMSO (35 mL) while under nitrogen atmosphere. After the addition was complete, the reaction was maintained at 55°-60° C. for 1 h. The reaction was extracted with Et2O (3×150 mL) and the combined Et2O extracts were treated in turn with 1N NaOH (150 mL), water (150 mL), 1N HCl (150 mL), water (150 mL), and a saturated NaCl solution (150 mL). The organic phase was dried with MgSO4, filtered, and concentrated under reduced pressure to yield a solid material. Recrystallization of the solid from hexane afforded b) (3.52 g, 21%).

1. customat 55-60° C.
2. additionAfter the addition
3. temperaturethe reaction was maintained at 55°-60° C. for 1 h
4. extractionThe reaction was extracted with Et2O (3×150 mL)
5. additionthe combined Et2O extracts were treated in turn with 1N NaOH (150 mL), water (150 mL), 1N HCl (150 mL), water (150 mL)
6. dry with materialThe organic phase was dried with MgSO4
7. filtrationfiltered
8. concentrationconcentrated under reduced pressure
9. customto yield a solid material
10. customRecrystallization of the solid from hexane afforded b) (3.52 g, 21%)

ORD record

ord-ab9553946cad46808d7da720215fef14

Source dataset

uspto-grants-1990_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US04954502