Iodine → 2,4-Dichloro-3-iodopyridine

Temperature

-78 °C

To a solution of 2,4-dichloropyridine (5.2 g, 35.137 mmol) and DIPEA (3.911 g, 38.651 mmol) in dry THF (40 ml) cooled at −78° C. under a nitrogen atmosphere, was added n-butyllithium (24.157 ml, 38.651 mmol, 1.6 M in hexanes) dropwise. The resulting reaction mixture was stirred at −78° C. for 45 min. and then a solution of iodine (9.81 g, 38.651 mmol) in dry THF (20 ml) was added dropwise. The mixture was stirred at −78° C. for 1 h. The mixture was allowed to warm to room temperature, diluted with EtOAc and quenched with NH4Cl (aqueous sat. solution) and Na2S2O3 (aqueous sat. solution). The combined organic extracts were separated, washed with NaHCO3 (aqueous sat. solution), dried (Na2SO4) and concentrated in vacuo. The crude product was purified by column chromatography (silica gel; Heptane/DCM up to 20% as eluent). The desired fractions were collected and concentrated in vacuo to yield intermediate compound D5 (7.8 g, 81%).

1. customThe resulting reaction mixture
2. stirringThe mixture was stirred at −78° C. for 1 h
3. temperatureto warm to room temperature
4. customquenched with NH4Cl (aqueous sat. solution) and Na2S2O3 (aqueous sat. solution)
5. customThe combined organic extracts were separated
6. washwashed with NaHCO3 (aqueous sat. solution)
7. dry with materialdried (Na2SO4)
8. concentrationconcentrated in vacuo
9. customThe crude product was purified by column chromatography (silica gel; Heptane/DCM up to 20% as eluent)
10. customThe desired fractions were collected
11. concentrationconcentrated in vacuo

ORD record

ord-00abb75a5f484622bac9a0cb6cf72d14

Source dataset

uspto-grants-2015_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08946205B2