Iodine → 5-Chloro-3-fluoro-4-iodopicolinonitrile

Temperature

-78 °C

To a cooled (−78° C.) solution of LDA (34.9 mmol, 1.1 equiv) in dry THF (200 mL) was added dropwise 5-chloro-3-fluoropicolinonitrile (5 g, 31.9 mmol) in dry THF (100 mL) over 15 min. The resulting mixture was stirred at −78° C. for an additional 15 min. A cooled (−78° C.) solution of iodine (12 g, 47 mmol, 1.5 equiv) in dry THF (72 mL) was poured rapidly into the reaction, and the resulting mixture was removed from the cold bath and stirred for 20 s. The reaction was then quenched by the addition of saturated aq. NaS2O3. The reaction mixture was diluted with ethyl acetate, and the organic layer was washed with brine, dried over sodium sulfate, filtered and concentrated in vacuo. Silica gel chromatography (5% EtOAc, 95% hexanes) provided the title compound as a yellow solid (7.4 g, 82%) which was characterized by 1HNMR.

1. additionwas poured rapidly into the reaction
2. customthe resulting mixture was removed from the cold bath
3. stirringstirred for 20 s
4. customThe reaction was then quenched by the addition of saturated aq. NaS2O3
5. additionThe reaction mixture was diluted with ethyl acetate
6. washthe organic layer was washed with brine
7. dry with materialdried over sodium sulfate
8. filtrationfiltered
9. concentrationconcentrated in vacuo

ORD record

ord-5a7adf4e7a3944cc854a80899d2ee640

Source dataset

uspto-grants-2011_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07989469B2