Dimethylamine → 6-Dimethylaminocarbonyl nicotinic acid

Participants

Reaction Conditions

Reaction Steps

To a suspension of pyridine-2,5-dicarboxylic acid dimethyl ester (10.1 g, 51.6 mmol) and MgBr2 (4.75 g, 25.8 mmol) in THF (200 mL) was added drop-wise a solution of dimethylamine (51.6 mL, 103.2 mmol, 2N in THF) at room temperature under nitrogen over a period of 10 min. The reaction mixture was stirred overnight and quenched with 1N HCl (52 mL) and H2O (50 mL), extracted with EtOAc (200 mL×3). The organic phase was washed with brine, dried over Na2SO4, filtered and concentrated. The crude residue was dissolved in a mixture of DMF (10 mL), AcOEt (50 mL), MeOH (20 mL) and DCM (50 mL), the formed solution was partially evaporated to produce a crystalline material, which was removed by filtration. The mother liquor was collected and evaporated to form a solid, which was dissolved in a mixture of THF (67 mL) and MeOH (67 mL). To this solution NaOH (2.95 g, 73.7 mmol) in H2O (33.5 mL) was added. The reaction mixture was heated at 40° C. for few hours, acidified (pH 3) to form a solid precipitate, which was collected by filtration and dried to afford the title compound 27 (4.937 g, 50% yield over two steps).

Provenance & Evidence