Chlorination of 4-amino-3-trifluoromethylbenzoic acid (I) gives 4-amino-3-chloro-5-trifluoromethylbenzoic acid (II), which is transformed in two steps to 4'-amino-3'-chloro-5'-trifluoromethylacetophenone (IV) by means of its acid chloride (III) and diethyl malonate. UV-catalyzed bromination with bromine in glacial acetic acid at 60-65 C gives the corresponding alpha-bromoketone (V). Reaction of (V) with tert-butylamine in isopropanol at 20 C leads to 4'-amino-2-tert-butylamino-3'-chloro-5'-trifluoromethylacetophenone (VI), which, without isolation, is reduced with sodium borohydride to the base (VII) of the title compound. The latter is obtained by treatment of (VII) with hydrochloric acid in diethyl ether. The optical isomers of mabuterol have been separated via the diastereomeric esters obtained by treating the racemate with (-)-methoxvcarbonyl chloride.

Chlorination of 4-amino-3-trifluoromethylbenzoic acid (I) gives 4-amino-3-chloro-5-trifluoromethylbenzoic acid (II), which is transformed in two steps to 4'-amino-3'-chloro-5'-trifluoromethylacetophenone (IV) by means of its acid chloride (III) and diethyl malonate. UV-catalyzed bromination with bromine in glacial acetic acid at 60-65 C gives the corresponding alpha-bromoketone (V). Reaction of (V) with tert-butylamine in isopropanol at 20 C leads to 4'-amino-2-tert-butylamino-3'-chloro-5'-trifluoromethylacetophenone (VI), which, without isolation, is reduced with sodium borohydride to the base (VII) of the title compound. The latter is obtained by treatment of (VII) with hydrochloric acid in diethyl ether. The optical isomers of mabuterol have been separated via the diastereomeric esters obtained by treating the racemate with (-)-methoxvcarbonyl chloride.