Selective ortho methylation of nitroheteroaryls by vicarious nucleophilic substitution.
An efficient and scalable three-step one-pot approach to 6-methyl-5-nitroisoquinoline (1) from inexpensive 5-nitroisoquinoline, utilizing the vicarious nucleophilic substitution (VNS) as a key step, is described. The optimized reaction conditions can be applied to a limited number of other aromatic and heteroaromatic nitro compounds. Attempts to understand the observed selectivity in the VNS step led to the discovery of two new reaction pathways under VNS conditions, one leading to an isoxazole and the other resulting in the formal cyclopropanation of an aromatic nitro compound.
Achmatowicz
Michał
M
Chemical Process Research and Development, Amgen Inc., One Amgen Center Drive, Thousand Oaks, California 91320-1799, USA. michala@amgen.com
Thiel
Oliver R
OR
Gorins
Gilles
G
Goldstein
Corinne
C
Affouard
Caroline
C
Jensen
Randy
R
Larsen
Robert D
RD