2,6-Difluorobenzoic acid → 3-(2,6-Difluorobenzoyl)amino-epsilon-caprolactam

1,1'-Carbonyldiimidazole (14.8 g), was added to a solution of 2,6-difluorobenzoic acid (12 g) in THF (200 ml) and followed by stirring for 15 mins. at room temperature. Then to the mixture was added 9.73 g of 3-amino-ε-caprolactam, and the whole was stirred for 5 hrs. at room temperature and the solvent was distilled off under reduced pressure. The residue was washed with methylenechloride to give 3-(2,6-difluorobenzoyl)amino-ε-caprolactam (13.5 g) as crude crystals. The crude crystals and phosphorus pentasulfide (8.96 g) were added to 200 ml of pyridine, and the whole was refluxed under stirring for 24 hrs. After cooling, the mixture was distilled to remove the solvent. To the residue was added a saturated sodium hydrogen carbonate solution and extracted with chloroform. The extract was washed with water, dried and concentrated under reduced pressure. The residue was purified by a column chromatography on silica gel and then recrystallized from a mixture of methylenechloride and isopropyl ether to give the title compound (3.19 g, 23.8%).

1. customat room temperature
2. stirringthe whole was stirred for 5 hrs
3. distillationat room temperature and the solvent was distilled off under reduced pressure
4. washThe residue was washed with methylenechloride

ORD record

ord-37dd55eb44434c7c91fb3bc5bfbd6e43

Source dataset

uspto-grants-1992_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05118806