Iodine → 2,3-Dichloro-4-iodopyridine

Temperature

-78 °C

Reaction performed under nitrogen atmosphere. 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., 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 minutes 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 room temperature 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 evaporated in vacuo. The crude residue was precipitated with heptane, filtered off and dried to yield compound D16 (8.21 g, 44%) as a pale cream solid.

1. customReaction
2. customThe resulting reaction mixture
3. stirringThe mixture was stirred at −78° C. for 30 minutes
4. temperatureto warm to room temperature overnight
5. customquenched with Na2S2O3 (aqueous sat. solution)
6. extractionextracted twice with EtOAc
7. washThe combined organic extracts were washed with NaHCO3 (aqueous sat. solution)
8. dry with materialdried (Na2SO4)
9. customevaporated in vacuo
10. customThe crude residue was precipitated with heptane
11. filtrationfiltered off
12. customdried
13. customto yield compound D16 (8.21 g, 44%) as a pale cream solid

ORD record

ord-106795c33c68451dafd2f7ee850a74ac

Source dataset

uspto-grants-2014_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08785486B2