Sulfuric Acid → HCID 178429279, compound

Participants

Reaction Conditions

Reaction Steps

A solution of 6-amino-2-bromo-4-methylpyridine (45.2 g, 0.24 mol) in water (100 ml) and concentrated sulphuric acid (43 g) at 0° C. was stirred and a solution of sodium nitrite (13.2 g; 0.19 mol) in water (20 ml) was added. After 2 hours, the reaction mixture was warmed to 60° C. and stirred for 1 hour. After cooling, the mixture was extracted with dichloromethane (200 ml). The solvent was removed in vacuo to afford 2-bromo-4-methyl-6-hydroxypyridine (20.2 g; 56%) as colorless crystals. Melting point 152° C. This material was mixed with tribromomethane (100 ml) and phosphoryl bromide (24 g) and heated to reflux for 3 hours. After cooling, the reaction mixture was quenched carefully with an aqueous 50% solution of sodiumhydroxide and the mixture extracted twice each with dichloromethane (100 ml). The solvent was removed in vacuo and the crude product purified by flash silica gel column chromatography using hexane/ethyl acetate (7/3). 2,6-Dibromo-4-methylpyridine (6.9 g; 25%) was obtained. Melting point 77° C. This compound (1.3 g; 5.2 mmol) was then converted using 3-hydroxybenzotrifluoride (1.4 ml; 10.7 mmol) and sodium hydride according to the procedure of Example 1 above to give 2,6-di-(3-trifluoromethylphenoxy)-4-methylpyridine as an oil (1.8 g; 84%).

Provenance & Evidence