title: Selective ortho methylation of nitroheteroaryls by vicarious nucleophilic substitution.
abstract: 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.
authors.affiliation: Chemical Process Research and Development, Amgen Inc., One Amgen Center Drive, Thousand Oaks, California 91320-1799, USA. michala@amgen.com
authors.forename: Michał
authors.initials: M
authors.lastname: Achmatowicz
authors.forename: Oliver R
authors.initials: OR
authors.lastname: Thiel
authors.forename: Gilles
authors.initials: G
authors.lastname: Gorins
authors.forename: Corinne
authors.initials: C
authors.lastname: Goldstein
authors.forename: Caroline
authors.initials: C
authors.lastname: Affouard
authors.forename: Randy
authors.initials: R
authors.lastname: Jensen
authors.forename: Robert D
authors.initials: RD
authors.lastname: Larsen