A straightforward synthesis of 2-methyl-3-trifluoromethyl-aniline has been developed from inexpensive 3-trifluoromethylaniline. Details of the synthetic steps are as follows:
(1) conversion of 3-trifluoromethylaniline to pivalylamino-3-trifluoromethylbenzene,
(2) conversion of pivalylamino-3-trifluoromethylbenzene to
pivalylamino-2-methyl-3-trifluoromethylbenzene,
(3) conversion of pivalylamino-2-methyl-3-trifluoromethylbenzene to 2-
methyl-3 -trifluoromethylaniline.
In attempting a one-step sythesis of 2-(2-methyl-3-
trifluoromethylanilino)nicotinic acid from 2-methyl-3-trifluoromethylaniline and 2-chloronicotinic acid, we unexpectedly obtained N-(2- methyl-3-trifluoromethyl)phenyl-2-hydroxynicotinamide.
A feasible bench-scale synthetic route to 2-(2-methyl-3-
trifluoromethylanilino)nicotinic acid, involving reaction of the methyl ester of 2-chloronicotinic acid with 2-methyl-3-trifluoromethylaniline, has been successfully developed.