Iodine chloride → 2-Bromo-5-iodopyridin-4-amine

Participants

Reaction Conditions

Reaction Steps

4-Amino-2-bromopyridine (22.8 g, 131.8 mmole) and sodium acetate (20.8 g 254 mmole) were stirred in acetic acid (82 mL) and a solution of iodine monochloride (1M in acetic acid, 134 mL, 134 mmole) was added. The mixture was stirred and heated at 75° C. for 3 hours. Most of the acetic acid was evaporated and the residue was partitioned between water (500 mL) and ethyl acetate (550 mL). The aqueous was again extracted with ethyl acetate (300 mL) The combined extracts were washed twice with 10% sodium carbonate solution (600, 300 mL), with 10% sodium thiosulfate solution (200 mL), with water and with brine, then dried and evaporated. This gave 40.3 g of a crude product mix. This was combined with the crude product from a reaction on 7.5 g of 4-amino-2-bromopyridine for purification. A large silica column (9 cm internal diameter with 28 cm bed of silica) was prepared in 5% ethyl acetate in dichloromethane. The crude material was applied in the same solvent. The column was eluted with 5% ethyl acetate in dichloromethane, with 10% ethyl acetate in dichloromethane and with 20% ethyl acetate in dichloromethane to give the desired isomer 5 (20.2 g, 38%): 1H-NMR (CDCl3, 500 MHz): δ 4.74 (br s, 2H, NH2), 6.80 (s, 1H), 8.34 (s, 1H); and subsequently with 1:1 ethyl acetate:dichloromethane to give 6 undesired isomer: 2-bromo-3-iodopyridin-4-amine 6 (19.3 g, 37%).

Provenance & Evidence