Potassium Phosphate, Tribasic → 4-[5-(3,5-Dichloropyridin-2-yl)-2-methylphenyl]-2,2,6,6-tetramethylpyran-3,5-dione

Participants

Reaction Steps

To a microwave vial is added 4-methyl-3-(2,2,6,6-tetramethyl-3,5-dioxo-tetrahydropyran-4-yl)phenylboronic acid (200 mg, 0.657 mmol), 2-bromo-3,5-dichloropyridine (149 mg, 0.657 mmol), palladium acetate (3.7 mg, 0.0164 mmol), tris(3-sulfophenyl)phosphine trisodium salt (22 mg, 0.0394 mmol) and potassium phosphate (697 mg, 3.28 mol), followed by a degassed solvent mixture of water/acetonitrile (1.6 ml, 2:1 ratio). The mixture is flushed with nitrogen then stirred at ambient temperature for 5 minutes before heating at 160° C. under microwave irradiation for 15 minutes. After cooling to room temperature the reaction is partitioned between 2M aqueous hydrochloric acid and dichloromethane, and the organic phase is separated. The aqueous phase is further extracted with dichloromethane and all organic fractions are combined then evaporated. The residue is purified by preparative reverse phase HPLC to give 4-[5-(3,5-dichloropyridin-2-yl)-2-methylphenyl]-2,2,6,6-tetramethylpyran-3,5-dione (113 mg).

Provenance & Evidence