2-Chloronicotinic acid → 2-Chloro-N-methoxy-N-methylnicotinamide

Temperature

25 °C

A solution of 2-chloronicotinic acid (20.0 g, 127 mmol) in N,N-dimethylformamide (600 mL, 0.21M) was treated with N,N-diisopropylethylamine (66 mL, 379 mmol), N,O-dimethylhydroxylamine hydrochloride (13.63 g, 140 mmol), and benzotriazole-1-yl-oxy-tris-(dimethylamino)-phosphonium hexafluorophosphate (84.25 g, 190 mmol). The reaction was stirred at 25° C. over 3 d. The resulting reaction was concentrated in vacuo, taken up in ethyl acetate (400 mL) and washed with a saturated aqueous ammonium chloride solution (2×250 mL), a saturated aqueous sodium bicarbonate solution (2×250 mL), and a saturated aqueous sodium chloride solution (250 mL). The organics were dried over magnesium sulfate, filtered and rinsed with ethyl acetate, and concentrated in vacuo. Flash chromatography (AnaLogix IntelliFlash 280 column chromatography, 400 g silica gel column, 25-50% ethyl acetate/hexanes) afforded 2-chloro-N-methoxy-N-methyl-nicotinamide (23.58 g, 93%) as a light yellow oil.

1. customThe resulting reaction
2. concentrationwas concentrated in vacuo
3. washwashed with a saturated aqueous ammonium chloride solution (2×250 mL)
4. dry with materialThe organics were dried over magnesium sulfate
5. filtrationfiltered
6. washrinsed with ethyl acetate
7. concentrationconcentrated in vacuo

ORD record

ord-ae7cc4beae2349608893351b3b7f3803

Source dataset

uspto-grants-2013_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08471027B2