Iodine → 3-Fluoro-4-iodopyridine-2-carbonitrile

Modified from WO 2004/019868. To a cold (0° C.) solution of diisopropylamine (4.84 mL, 32 mmol) in THF (82.3 mL) was added n-butyllithium (12.8 mL, 2.5 M in hexanes, 32 mmol) dropwise. The resultant solution was stirred at 0° C. for 15 minutes to give a 0.32 M stock solution of LDA. To a cold (−78° C.) solution of LDA (74 mL, 0.32 M in THF, 23.7 mmol) in THF (50 mL) was added 3-fluoro-2-pyridinecarbonitrile (2.4 g, 19.7 mmol) (Sakamoto et. al. Chem. Pharm. Bull. 1985, 33, 565) as a solution in THF (20 mL). After 15 minutes, a solution of I2 (5.49 g, 21.6 mmol) in THF (20 mL) was added rapidly and the resultant suspension was stirred for 20 minutes at −78° C. The reaction mixture was quenched by the addition of water and warmed to ambient temperature. Ethyl acetate was added and the organic layer was washed successively with sodium thiosulfate, and brine. The aqueous layer was extracted with ethyl acetate and the combined organics were dried over sodium sulphate. Filtration and concentration followed by purification by silica gel chromatography provided 3-fluoro-4-iodo-2-pyridinecarbonitrile (3.6 g, 73%) as a white solid. 1H NMR (400 MHz, CDCl3) δ 8.14 (d, J=4.8 Hz, 1 H), 7.98 (t, J=4.8 Hz, 1 H).

1. customThe reaction mixture was quenched by the addition of water
2. additionEthyl acetate was added
3. washthe organic layer was washed successively with sodium thiosulfate, and brine
4. extractionThe aqueous layer was extracted with ethyl acetate
5. dry with materialthe combined organics were dried over sodium sulphate
6. filtrationFiltration and concentration
7. customfollowed by purification by silica gel chromatography

ORD record

ord-0ec8ba99ae34408d962fdabee8d38f10

Source dataset

uspto-grants-2014_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08691991B2