Facile one-pot synthesis of N-difluoromethyl-2-pyridone derivatives.
[reaction: see text] A novel one-pot synthesis of N-difluoromethyl-2-pyridones is described. N-(Pyridin-2-yl)acetamide derivatives were excellent precursors for the preparation of N-difluoromethyl-2-pyridone derivatives. Difluoromethylation of 2-acetaminopyridine derivatives was achieved with sodium chlorodifluoroacetate as a difluorocarbene source in the presence of a catalytic amount of 18-crown-6. Subsequent in situ hydrolysis of resultant 1,2-dihydro-2-acetimino-1-difluoromethylpyridines proceeded under mild acidic conditions to afford the corresponding N-difluoromethyl-2-pyridones in moderate to good yields.
Ando
Makoto
M
Tsukuba Research Institute, Banyu Pharmaceutical Company, Ltd., Okubo 3, Tsukuba 300-2611, Japan. makoto_ando@merck.com
Wada
Toshihiro
T
Sato
Nagaaki
N
D002384:Catalysis; D020650:Combinatorial Chemistry Techniques; D015394:Molecular Structure; D011728:Pyridones / Q000138:chemical synthesis* / Q000737:chemistry*
D011728:Pyridones