Acetic Acid → METHYL 2-METHOXY-6-METHYLPYRIDINE-3-CARBOXYLATE

Participants

Reaction Steps

To a stirred solution of 2-chloro-6-methyl-nicotinic acid methyl ester (10.4 g, 56.52 mmol) in MeOH under nitrogen is added a solution of sodium (2.58 g, 113.04 mmol) in methanol (80.0 mL) (sodium metal is dissolved in methanol under a nitrogen atmosphere) at room temperature. The reaction mixture is refluxed overnight. The reaction is cooled to room temperature and the pH is adjusted to pH=7 with acetic acid. The reaction mixture is diluted with ethyl acetate (100 mL) and water (30 mL). The organic layer is separated and the aqueous layer is extracted with ethyl acetate (2×75 mL). The combined organic extracts are dried over Na2SO4, filtered, and concentrated to give crude product. Yield: 7.25 g (71%). 1H NMR (400 MHz, CDCl3), δ8.066-8.047 (d, J=7.6 Hz, 1H), 6.782-6.764 (d, J=7.2 Hz, 1-1H), 4.029 (s, 3H), 3.879 (s, 3H), 2.483 (s, 3H); ES/MS m/z 182.2 [M+H]+.

Provenance & Evidence