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

Participants

Reaction Steps

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).

Provenance & Evidence