4-Methylmorpholine → 6-Chloro-N-methoxy-N-methylnicotinamide

To a solution of 6-chloro-nicotinic acid (94.5 g, 0.6 mol) in dichloromethane (1000 mL) was added N-methyl morpholine (181.8 g, 1.8 mol) followed by iso-butyl chloroformate (81.9 g, 0.6 mol) at −25° C. under 1\2 atmosphere. The mixture was stirred for 15 minutes and then O,N-dimethyl hydroxylamine hydrochloride (64.35 g, 0.66 mol) was added. The mixture was stirred for 30 min at −25° C. and warmed to room temperature slowly. The mixture was stirred for an additional hour at room temperature and a saturated solution of NaHCO3 (800 mL) was added. The separated aqueous layer was extracted with dichloromethane (500 mL×3). The combined organic layers were washed with water and brine. The solvent was evaporated to give the crude product, which was purified by column chromatography to give the pure product 6-chloro-N-methoxy-N-methyl-nicotinamide as a white solid (56 g, 46.6%).

1. stirringThe mixture was stirred for 30 min at −25° C.
2. stirringThe mixture was stirred for an additional hour at room temperature
3. extractionThe separated aqueous layer was extracted with dichloromethane (500 mL×3)
4. washThe combined organic layers were washed with water and brine
5. customThe solvent was evaporated
6. customto give the crude product, which
7. customwas purified by column chromatography

ORD record

ord-f7e4870a8184414caaeeb0b8b3531893

Source dataset

uspto-grants-2013_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08524910B2