Iodine → Lithium diisopropylamide

Participants

Reaction Conditions

Reaction Steps

Prepared according to J. Org. Chem. 1993, 7832: A solution of lithium diisopropylamide was prepared by addition of n-BuLi (46.4 ml, 2.5 M in hexanes, 0.12 mol) to a solution of diisopropyl amine (15 ml, 0.12 mol) in of anhydrous THF (200 ml) at 0° C. After stirring for ten minutes the solution was cooled to −78° C. Using a syringe pump 2-fluoropyridine (10 ml, 0.12 mol) was added neat over 2 min. The reaction mixture was stirred for 4 h at this temperature. A white precipitate formed. A solution of iodine (29.5 gm, 0.12 mol) in of anhydrous THF (100 ml) was added over 40 min via syringe pump while the reaction was kept at −78° C. The reaction mixture changed from white to yellow and finally to orange in color during this addition. The reaction mixture is quenched at −78° C. by adding of water (5 ml) followed by carefully pouring the mixture into an 1:1 mixture of saturated aqueous sodium bicarbonate and saturated aqueous sodium thiosulfate. The product was extracted into ether and the organic layer was washed with brine and then dried over Na2SO4 and evaporated in vacuo. The residue 22.2 gm (86%), which solidified, was purified by chromatography on silica gel eluting with 9/1 hexane/ethyl acetate to afford of the desired 2-fluoro-3-iodopyridine contaminated with 2-fluoro-4-iodopyridine (21 gm). 1H NMR (CDCl3, 400 MHz) δ 8.17 (m, 2H), 6.95 (m, 1H); APCl MS m/z 224 (M)+.

Provenance & Evidence