Reaction #316834

Reaction equation

ammonia

methyl 5-bromo-2-hydroxynicotinate

2-hydroxynicotinic acid

phenylboronic acid

→

5-bromo-3-methoxycarbonyl-1-phenyl-1,2-dihydropyridin-2-one

Yield 60.1%

Solvents

pyridine

tetrahydrofuran

Conditions

Workup

1. 1
   Extractionthe solution was extracted with chloroform
2. 2
   WashThe organic layer was washed with brine
3. 3
   Dryingdried over anhydrous magnesium sulfate
4. 4
   OtherThe solvent was evaporated
5. 5
   Otherthe residue obtained as a solid
6. 6
   Washwas washed with diethyl ether

Procedure

4.5 g of methyl 5-bromo-2-hydroxynicotinate synthesized by a known method from 2-hydroxynicotinic acid, and 4.7 g of phenylboronic acid were dissolved in 200 ml of tetrahydrofuran. To the mixture were added 705 mg of copper acetate and 1 ml of pyridine, followed by stirring at room temperature for 3 nights in a flow of air. Aqueous ammonia was added to the reaction solution, and the solution was extracted with chloroform. The organic layer was washed with brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated, and the residue obtained as a solid was washed with diethyl ether, to obtain 3.59 g of 5-bromo-3-methoxycarbonyl-1-phenyl-1,2-dihydropyridin-2-one as white crystals. 3.2 g of the product was dissolved in 100 ml of dimethylformamide, to which 7.7 g of tri-N-butyl-(2-pyridyl)tin [CAS No. 59020-10-9] and 240 mg of tetrakistriphenylphosphine palladium were added, followed by stirring at 110° C. for 3 hours in nitrogen atmosphere. After cooling to room temperature, the reaction solution was poured into water, extracted with ethyl acetate. Then, the extract was successively washed with water and brine, dried over anhydrous magnesium sulfate, and then filtered through NH silica gel and silica gel. Then, the filtrate was evaporated, and the resulting precipitates were washed with ether and hexane, and dried, to give 1.59 g of the title compound.

Source