Dimethylformamide → 6-Chloro-N-methoxy-N-methylnicotinamide

Under ice cooling, 6-chloronicotinic acid (5.00 g) was suspended in dichloromethane (150 ml), followed by the addition of a catalytic amount of N,N-dimethylformamide and oxalyl chloride (5.30 ml). The resulting mixture was stirred at room temperature for 23 hours. The residue obtained by concentrating the reaction mixture was dissolved in dichloromethane (100 ml), followed by the addition of N,O-dimethylhydroxylamine hydrochloride (6.18 g) and triethylamine (13.3 ml) under ice cooling. After stirring at room temperature for 6 hours, the reaction mixture was diluted with dichloromethane (150 ml), washed with a saturated aqueous solution of sodium bicarbonate, water and saturated aqueous NaCl solution and then dried over anhydrous magnesium sulfate. The residue obtained by distilling off the solvent under reduced pressure was purified by chromatography on a silica gel column (hexane:ethyl acetate=2:1), whereby the title compound (6.08 g, 96%) was obtained.

1. customThe residue obtained
2. concentrationby concentrating the reaction mixture
3. dissolutionwas dissolved in dichloromethane (100 ml)
4. additionfollowed by the addition of N,O-dimethylhydroxylamine hydrochloride (6.18 g) and triethylamine (13.3 ml) under ice cooling
5. stirringAfter stirring at room temperature for 6 hours
6. additionthe reaction mixture was diluted with dichloromethane (150 ml)
7. washwashed with a saturated aqueous solution of sodium bicarbonate, water and saturated aqueous NaCl solution
8. dry with materialdried over anhydrous magnesium sulfate
9. customThe residue obtained
10. distillationby distilling off the solvent under reduced pressure
11. customwas purified by chromatography on a silica gel column (hexane:ethyl acetate=2:1), whereby the title compound (6.08 g, 96%)
12. customwas obtained

ORD record

ord-f5de0b83a1d04f03b25baad77225f866

Source dataset

uspto-grants-2004_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06747023B1