Iodine → 2,3-Dichloro-4-iodopyridine

Temperature

-78 °C

To a solution of n-butyllithium (27.6 ml, 69 mmol, 2.5 M in hexanes) in dry Et2O (150 ml) cooled at −78° C., under a nitrogen atmosphere, was added 2,2,6,6-tetramethylpiperidine (11.64 ml, 69 mmol), dropwise. The resulting reaction mixture was stirred at −78° C. for 10 min., and then a solution of 2,3-dichloropyridine (10 g, 67.57 mmol) in dry THF (75 ml) was added dropwise. The mixture was stirred at −78° C. for 30 min. and then a solution of iodine (25.38 g, 100 mmol) in dry THF (75 ml) was added. The mixture was allowed to warm to r.t. overnight, quenched with Na2S2O3 (aqueous sat. solution) and extracted twice with EtOAc. The combined organic extracts were washed with NaHCO3 (aqueous sat. solution), dried (Na2SO4) and concentrated in vacuo. The crude residue was precipitated with heptane, filtered off and dried to yield intermediate compound D10 (8.21 g, 44%) as a pale cream solid.

1. customThe resulting reaction mixture
2. stirringThe mixture was stirred at −78° C. for 30 min.
3. temperatureto warm to r.t. overnight
4. customquenched with Na2S2O3 (aqueous sat. solution)
5. extractionextracted twice with EtOAc
6. washThe combined organic extracts were washed with NaHCO3 (aqueous sat. solution)
7. dry with materialdried (Na2SO4)
8. concentrationconcentrated in vacuo
9. customThe crude residue was precipitated with heptane
10. filtrationfiltered off
11. customdried
12. customto yield intermediate compound D10 (8.21 g, 44%) as a pale cream solid

ORD record

ord-32685ed52af847d3885f0422591e2bef

Source dataset

uspto-grants-2016_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09226930B2