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 minutes. The resulting mixture was stirred at −78° C. for an additional 15 minutes. 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 20s. The reaction was then quenched by the addition of saturated aq. NaS2O3. The reaction mixture was diluted with ethyl acetate, and 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 HNMR.

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

ORD record

ord-d2ebe01cf6a443ff8123095093c5c2c9

Source dataset

uspto-grants-2010_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07851484B2