2-Chloro-N-methoxy-N-methylisonicotinamide → 1-(2-Chloropyridin-4-yl)ethan-1-one

Participants

Reaction Steps

To a solution of 2-chloro-N-methoxy-N-methyl-isonicotinamide (20 g, 100 mmol) in THF (100 mL) is added a solution of methyl magnesium bromide (3M in THF, 73 mL, 220 mmol) at −40° C. After stirring the mixture for 2 hours at this temperature, the mixture is quenched with ice-cooled saturated ammonium chloride solution (300 mL). The organic phase is separated. The aqueous layer is extracted with ethyl acetate (2×150 mL). The combined organic layers are washed with brine and dried over sodium sulfate, filtered and concentrated under reduced pressure to give 4-acetyl-2-chloro-pyridine (14.4 g), which is used for the next reaction without further purification; ESI-MS (m/z): 156.0 (M++H).

Provenance & Evidence