Hydrochloric Acid → ethyl (3-{3-[5-(2',6'-dimethylbiphenyl-2-yl)-2-oxopyridin-1(2H)-yl]propyl}phenoxy)acetate

Participants

Reaction Conditions

Reaction Steps

A mixture of ethyl (3-{3-[5-(2-bromophenyl)-2-oxopyridin-1(2H)-yl]propyl}phenoxy)acetate (255 mg), (2,6-dimethylphenyl)boronic acid (122 mg), 2′-(dicyclohexylphosphino)-N,N-dimethylbiphenyl-2-amine (26 mg), tripotassium phosphate (345 mg) and palladium (II) acetate (4 mg) in toluene (10 mL) was stirred under N2 gas atmosphere at 100° C. for 40 hours and cooled to ambient temperature. To the mixture was added 2′-(dicyclohexylphosphino)-N,N-dimethylbiphenyl-2-amine (26 mg), (2,6-dimethylphenyl)boronic acid (50 mg) and palladium (II) acetate (4 mg) and the mixture was stirred under N2 gas atmosphere at 100° C. for 60 hours and cooled to ambient temperature. The reaction mixture was acidified with 1M HCl aqueous solution and extracted with EtOAc. The organic layer was washed with brine, dried over anhydrous MgSO4, filtered and evaporated in vacuo. The residue was dissolved in EtOH (10 mL). To the solution was added concentrated H2SO4(1.5 mL) and the mixture was refluxed for 1.5 hours and cooled to ambient temperature. The reaction mixture was neutralized with saturated aqueous NaHCO3 solution and extracted with EtOAc. The organic layer was washed with brine, dried over anhydrous MgSO4, filtered and evaporated in vacuo. The residue was purified by silica gel column chromatography (n-hexane:EtOAc=70:30) to give ethyl (3-{3-[5-(2′,6′-dimethylbiphenyl-2-yl)-2-oxopyridin-1(2H)-yl]propyl}phenoxy)acetate (55.1 mg) as a colorless oil.

Provenance & Evidence