Methanamine, N-methoxy-, hydrochloride (1:1) → N-Methoxy-N,2,6-trimethylisonicotinamide

Participants

Reaction Conditions

Reaction Steps

Under argon a suspension of 2,6-dimethyl-isonicotinic acid butyl ester (16.67 g) and N,O-dimethylhydroxylamine hydrochloride (12.2 g) in THF (150 mL) was cooled down to −20° C. A solution of isopropylmagnesium chloride (2M in THF, 120.6 mL) was added over 20 min maintaining the temperature below −5° C. The mixture was stirred for 2.5 hours at −10° C. and quenched with a saturated aqueous solution of NH4Cl (200 mL). The phases were separated and the inorganic one was extracted with EtOAc (2×). The combined organic layers were washed with brine, dried over Na2SO4, filtered and concentrated in vacuo. Column chromatography on silica gel (EtOAc/n-heptane 2:1 to EtOAc) yielded the title compound (14.1 g, 90%) as a yellow liquid, MS (ESI+): m/z=195.0 [M+H]+.

Provenance & Evidence