Hydrochloric Acid → Methyl 2-Benzoylnicotinate

Participants

Reaction Conditions

Reaction Steps

To a suspension of 29.84 grams 2,3-pyridinedicarboxylic anhydride in 300 ml THF under an atmosphere of dry nitrogen was added dropwise 200 ml of a 1.0M solution of phenyl magnesium bromide at -78° C. After two hours the reaction mixture was warmed to 21° C. and stirred overnight. The mixture was then refluxed for 24 hours, cooled, treated with 220 ml 1N HCl, stirred one hour, and transferred to separatory funnel. The THF layer was dried over magnesium sulfate, filtered and concentrated under vacuum to give 44.26 grams crude material which was then dissolved in 400 ml anhydrous methanol. To this solution was carefully added 10 ml conc. H2SO4. The solution was then refluxed overnight under an atmosphere of nitrogen. The mixture was cooled and concentrated under vacuum, neutralized with saturated sodium carbonate solution, and extracted with dichloromethane. The mixture was then dried over magnesium sulfate, filtered and concentrated under vacuum to give 42.71 grams crude material. The crude material was dissolved with a minimum amount of dichloromethane and treated by silica gel [column chromatography, eluted with ethyl acetate/hexane (1:3)] to give 12.35 grams (26% yield) of the desired methyl 2-benzoylnicotinate as a white powder. Characteristic analytical data are as follows: mp 74° C.; TLC in 1:3 EtOAc/Hex; 1H NMR (CDCl3, 300 MHz) δ3.77 (s, 3H), 7.45-7.85 (m, 6H), 8.37 (dd, 1H, J=8.0, 1.6 Hz), 8.82 (dd, 1H, J=4.8, 1.5 Hz); mass spectrum (EI), m/e 421.

Provenance & Evidence