Iodine → 2-Fluoro-3-iodo-5-methylpyridine

Temperature

-78 °C

A solution of 2M LDA in THF (371 mL, 742 mmol) was added to THF (1400 mL) at −78° C. under an atmosphere of nitrogen. To this stirred, cooled solution was added 2-fluoro-5-methylpyridine (75.0 g, 67.6 mmol) in THF (280 mL) dropwise. The reaction mixture was allowed to stir at −78° C. for 2 h and then a solution of iodine (171.5 g, 67.6 mmol) in THF (560 mL) was added dropwise. The reaction mixture was allowed to stir at −78 for 2 h and then diluted with water (875 mL). The mixture was allowed to warm to rt and was then extracted with EtOAc. The organic solutions were combined, washed with brine, dried over Na2SO4, filtered and concentrated. The residue was purified by column chromatography to give 2-fluoro-3-iodo-5-methylpyridine (80 g, 50%).

1. temperatureTo this stirred, cooled solution
2. stirringto stir at −78 for 2 h
3. temperatureto warm to rt
4. extractionwas then extracted with EtOAc
5. washwashed with brine
6. dry with materialdried over Na2SO4
7. filtrationfiltered
8. concentrationconcentrated
9. customThe residue was purified by column chromatography

ORD record

ord-16a6e59ce02b4fb3b5c3aec2a9000e59

Source dataset

uspto-grants-2014_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08859768B2