4-Methylmorpholine → N-Methoxy-6,N-dimethyl-nicotinamide

To a solution of 6-methylnicotinic acid (5.00 g, 36.5 mmol) in DMF (150 mL), 1-hydroxybenzotriazole (4.92 g, 36.5 mmol), N-ethyl-N-(3-dimethylaminopropyl) carbodiimide hydrochloride (8.38 g, 45.7 mmol) and 4-methylmorpholine (16.0 mL, 145.8 mmol) were added under argon atmosphere. The mixture was stirred at room temperature for 30 minutes after which N,O-dimethylhydroxylamine hydrochloride was added (3.55 g, 36.5 mmol). The reaction mixture was stirred at room temperature overnight. The solvent was evaporated off. The residue was dissolved in a mixture of CHCl3 and 0.2 N NaHCO3. The phases were separated and the aqueous phase was extracted with CHCl3. The organic phase was dried over Na2SO4 and concentrated to dryness. The product was purified by chromatography on silica gel using hexane-EtOAc mixtures of increasing polarity as eluent, to afford 1.11 g of the desired product (yield: 29%).

1. additionwas added (3.55 g, 36.5 mmol)
2. customThe solvent was evaporated off
3. dissolutionThe residue was dissolved in a mixture of CHCl3 and 0.2 N NaHCO3
4. customThe phases were separated
5. extractionthe aqueous phase was extracted with CHCl3
6. dry with materialThe organic phase was dried over Na2SO4
7. concentrationconcentrated to dryness
8. customThe product was purified by chromatography on silica gel
9. temperatureof increasing polarity as eluent

ORD record

ord-0ea530a68de14ebfa227f4f0f3b031f8

Source dataset

uspto-grants-2013_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08536194B2