Isonicotinic Acid → N-Methoxy-N-methylisonicotinamide

To a stirred solution of isonicotinic acid (20.0 g, 162 mmol) in DCM (400 mL) were added HATU (92.6 g, 243 mmol), N-methoxy methylamine (17.24 g, 178 mmol) and TEA (68.7 mL, 487 mmol) at RT under nitrogen atmosphere. The reaction mixture was then stirred at RT for 12 h. The reaction mixture was diluted with water and the aqueous layer was extracted with DCM (3×500 mL). The combined organic extracts were washed with water (150 mL), brine (150 mL), dried over anhydrous Na2SO4, filtered and concentrated in vacuo to obtain the crude product. The crude material was purified via silica gel column chromatography eluting with 30-40% EtOAc in Hexane to afford to afford N-methoxy-N-methylisonicotinamide (15.0 g, 55%) as an oil.

1. extractionthe aqueous layer was extracted with DCM (3×500 mL)
2. washThe combined organic extracts were washed with water (150 mL), brine (150 mL)
3. dry with materialdried over anhydrous Na2SO4
4. filtrationfiltered
5. concentrationconcentrated in vacuo
6. customto obtain the crude product
7. customThe crude material was purified via silica gel column chromatography
8. washeluting with 30-40% EtOAc in Hexane
9. customto afford

ORD record

ord-339fc630faaa4167a04a08a223cf1fba

Source dataset

uspto-grants-2011_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08071595B2