Iodine → 4-Iodo-6-methoxynicotinonitrile

Temperature

-78 °C

At −78° C., 19.4 ml of lithium diisopropylamide (2 molar in THF/heptane/ethylbenzene, 1.3 eq.) were added to a solution of 4.0 g (29.8 mmol) of 6-methoxypyridine-3-carbonitrile in 120 ml of THF, and the mixture was stirred at −78° C. for 1 h. At −78° C., a solution of 9.1 g (35.8 mmol) of iodine in 20 ml of THF was then added, and the reaction mixture was stirred at −78° C. for 1 h and then carefully added to saturated aqueous ammonium chloride solution. After addition of ethyl acetate, the reaction mixture was extracted three times with ethyl acetate. The combined organic phases were dried (magnesium sulphate), filtered and concentrated under reduced pressure. The crude product was purified by flash chromatography (silica gel 60, mobile phase: cyclohexane/ethyl acetate mixtures). Yield: 4.0 g (purity 92%, 48% of theory)

1. stirringthe reaction mixture was stirred at −78° C. for 1 h
2. extractionthe reaction mixture was extracted three times with ethyl acetate
3. dry with materialThe combined organic phases were dried (magnesium sulphate)
4. filtrationfiltered
5. concentrationconcentrated under reduced pressure
6. customThe crude product was purified by flash chromatography (silica gel 60, mobile phase: cyclohexane/ethyl acetate mixtures)

ORD record

ord-7152e453c2da495a95d1b2cf28d7baa1

Source dataset

uspto-grants-2016_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09434690B2