Yield:885952-12-5 95%

Reaction Conditions:

with sulfuric acid;iodine;acetic acid;periodic acid in water at 80; for 1.5 h;

Steps:

2.2.1

To a flask was added 4,6-dimethylpyridin-2-amine (12.2 g, 100 mmol), periodic acid (3.87 g, 17 mmol) and iodine (10.4 g, 41 mmol). Acetic acid (100 mL), water (20 mL) and H₂S0₄ (3 mL) were then added, and the reaction was heated to 80 °C for a period of 1.5 h, after which time the reaction was cooled to rt and water (10 mL) and heptanes (50 mL) were added. The layers were separated and the aqueous phase was extracted with heptanes (50 mL). The aqueous phase was concentrated under reduced pressure, and then EtOAc (150 mL) and water (5 mL) were added. To this mixture was added 8 M NaOH (3 x 20 mL portions), and then the layers were separated. The organic phase was washed with saturated aqueous sodium bicarbonate and saturated aqueous sodium chloride and then dried (Na₂S0₄), filtered and concentrated under reduced pressure to an orange solid. The solid was slurried in EtOAc (45 mL) and then filtered to yield 5-iodo-4,6-dimethylpyridin-2-amine (14.2 g, 95%) as a white solid. MS ESI calcd. for C7H₉IN2 249, found 249.

References:

WO2014/153280,2014,A1 Location in patent:Paragraph 00156