Iodine → 2,4-Dichloro-3-iodopyridine

Temperature

-78 °C

To a solution of 2,4-dichloropyridine (5.2 g, 35.14 mmol) and diisopropylamine (3.91 g, 38.65 mmol) in dry THF (40 mL) cooled at −78° C. under a nitrogen atmosphere, was added n-butyllithium (24.16 mL, 38.65 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., allowed to warm to r.t., diluted with EtOAc and quenched with NH4Cl (aqueous sat. solution) and Na2S2O3 (aqueous sat. solution). The organic layer was separated, washed with NaHCO3 (aqueous sat. solution), dried (Na2SO4) and concentrated in vacuo. The crude product was purified by column chromatography (silica gel; DCM in heptane 0/100 to 20/80). The desired fractions were collected and concentrated in vacuo to yield intermediate compound I-1 (7.8 g, 81%).

1. customThe resulting reaction mixture
2. stirringThe mixture was stirred at −78° C. for 1 h.
3. temperatureto warm to r.t.
4. customquenched with NH4Cl (aqueous sat. solution) and Na2S2O3 (aqueous sat. solution)
5. customThe organic layer was 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; DCM in heptane 0/100 to 20/80)
10. customThe desired fractions were collected
11. concentrationconcentrated in vacuo
12. customto yield intermediate compound I-1 (7.8 g, 81%)

ORD record

ord-be266cb8ac474d1b88d68b6af13eebfc

Source dataset

uspto-grants-2015_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09012448B2