Iodine → 2,4-Dichloro-3-iodopyridine

Temperatur

-78 °C

To a solution of 2,4-dichloropyridine (5.2 g, 35.137 mmol) and diisopropylamine (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., then a solution of iodine (9.81 g, 38.651 mmol) in dry THF (20 ml) was added dropwise and the mixture was further stirred at −78° C. for 1 h. The mixture was 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; Heptane/DCM up to 20% as eluent). The desired fractions were collected and concentrated in vacuo to yield intermediate compound D12 (7.8 g, 81%)

1. customThe resulting reaction mixture
2. stirringthe mixture was further 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; Heptane/DCM up to 20% as eluent)
10. customThe desired fractions were collected
11. concentrationconcentrated in vacuo
12. customto yield intermediate compound D12 (7.8 g, 81%)

ORD-Eintrag

ord-99e9d5119a154c7ba7ad5f515a0b4151

Quelldatensatz

uspto-grants-2014_05

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08716480B2