Iodine → 3,5-Difluoro-4-iodopicolinonitrile

Temperature

-78 °C

Diisopropylamine (5.60 mL, 39.27 mmol) in THF (40 mL) was cooled to 0° C. and n-BuLi (12.56 mL, 31.4 mmol) was added slowly. After 30 minutes, the reaction was cooled to −78° C. and 3,5-difluoropicolinonitrile (4.0 g, 28.6 mmol) in THF (25 mL) was added and the solution was stirred for 30 minutes. A solution of iodine (10.87 g, 42.8 mmol) in THF (35 mL) was cooled to (−78° C.) and added all at once. After about 30 seconds the reaction was quenched with sodium thiosulfate solution (10 mL) and water (20 mL). The mixture was extracted with EtOAc (2×150 mL) and the combined organics were extracted with brine, dried over Na2SO4 and concentrated to give a residue which was purified using silica column chromatography eluted with hexanes/EtOAc to give 3,5-difluoro-4-iodopicolinonitrile.

1. additionadded all at once
2. customAfter about 30 seconds the reaction was quenched with sodium thiosulfate solution (10 mL) and water (20 mL)
3. extractionThe mixture was extracted with EtOAc (2×150 mL)
4. extractionthe combined organics were extracted with brine
5. dry with materialdried over Na2SO4
6. concentrationconcentrated
7. customto give a residue which
8. customwas purified
9. washeluted with hexanes/EtOAc

ORD record

ord-b96818c025c74a00af0a5db262f3c8e3

Source dataset

uspto-grants-2015_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09073918B2