Ethanol → Ethyl 2-chloro-6-methoxyisonicotinate

Participants

Reaction Conditions

Reaction Steps

To a previously sonicated suspension of 2-chloro-6-methoxyisonicotinic acid (4.0 g, 21 mmol) in ethanol (50 mL) was added thionyl chloride (4.64 mL, 64.0 mmol) at 0° C. The reaction mixture was stirred at 0° C. for 2 h and then at room temperature for 18 h. Thionyl chloride (4.64 mL, 64.0 mmol) was slowly added and the mixture was stirred at room temperature for 4 h. The reaction mixture was quenched by slowly pouring into a saturated aqueous solution of sodium bicarbonate (200 mL). Ice was added to the mixture to lower the temperature. The mixture was extracted with diethyl ether (150 mL×2). The combined organics were washed with brine, dried over sodium sulfate, filtered and concentrated under reduced pressure to afford a clear syrup as crude product. The crude product was dried for 2 h under high vacuum while heating to 80° C. The resulting residue was concentrated from toluene (500 mL) to afford ethyl 2-chloro-6-methoxyisonicotinate as an off white solid (3.205 g). 1H NMR (400 MHz, CDCl3) δ 1.40 (s, 3H), 3.98 (s, 3H), 4.39 (s, 2H), 7.22 (s, 1H), 7.44 (s, 1H).

Provenance & Evidence