Iodine → 2-Chloro-5-fluoro-4-iodopyridine

Lithium N,N-diisopropyl amide (2M THF/ethylbenzene/heptane solution) (2.9 ml) was mixed with THF (20 ml), and a THF (5 ml) solution containing 2-chloro-5-fluoropyridine (500 mg) was added to the mixture in a nitrogen atmosphere at −75° C., followed by stirring for 3 hours. Subsequently, a THF (5 ml) solution containing iodine (1.16 g) was added to the mixture, followed by stirring at −75° C. for 1 hour. Next, water/THF (2 ml/8 ml), water (10 ml), and a 3M sodium thiosulfate aqueous solution were added to the reaction solution at −75° C., −50° C., and −35° C., respectively. The reaction solution was adjusted to room temperature, followed by extraction with ethyl acetate. The organic layers were washed with saturated saline and dried over anhydrous sodium sulfate. The solvent was distilled away under reduced pressure and the obtained residue was purified by silica gel chromatography (n-hexane:ethyl acetate=20:1 to 10:1). A white solid of 2-chloro-5-fluoro-4-iodopyridine (457 mg) was thus obtained.

1. additionwas added to the mixture in a nitrogen atmosphere at −75° C.
2. additionwas added to the mixture
3. stirringby stirring at −75° C. for 1 hour
4. custom−35° C.
5. customwas adjusted to room temperature
6. extractionfollowed by extraction with ethyl acetate
7. washThe organic layers were washed with saturated saline
8. dry with materialdried over anhydrous sodium sulfate
9. distillationThe solvent was distilled away under reduced pressure
10. customthe obtained residue was purified by silica gel chromatography (n-hexane:ethyl acetate=20:1 to 10:1)

ORD record

ord-7cae92e8ed764123b1b4f6c59d26a906

Source dataset

uspto-grants-2015_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09051310B2