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レコード

ord-f7e4870a8184414caaeeb0b8b3531893

出典データセット

uspto-grants-2013_09

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US08524910B2