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

HRID 1617469Notes

Reaction equation

C(O[C:6](=[O:15])[C:7]1[CH:12]=[C:11]([CH3:13])[N:10]=[C:9]([CH3:14])[CH:8]=1)CCC.Cl.[CH3:17][NH:18][O:19][CH3:20].C([Mg]Cl)(C)C>C1COCC1>[CH3:20][O:19][N:18]([CH3:17])[C:6](=[O:15])[C:7]1[CH:8]=[C:9]([CH3:14])[N:10]=[C:11]([CH3:13])[CH:12]=1

Participants

Conditions

Temperature: -20 °C

Procedure

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]+.

Workup

temperaturemaintaining the temperature below −5° C
customquenched with a saturated aqueous solution of NH4Cl (200 mL)
customThe phases were separated
extractionthe inorganic one was extracted with EtOAc (2×)
washThe combined organic layers were washed with brine
dry with materialdried over Na2SO4
filtrationfiltered
concentrationconcentrated in vacuo

Sources & evidence

ORD record: ord-1b24f2b19cdd4bfc8b3fc57bd8f8c16c
Source dataset: uspto-grants-2014_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08765730B2

Reaction notes

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