Mabuterol is a selective β2 adrenoreceptor agonist.

Synthesis

The halogenation of 2-(trifluoromethyl)aniline (1) with iodine and sodium bicarbonate produces 2-amino-5-iodobenzotrifluoride (2). Protection with acetic anhydride followed by nucleophilic aromatic substitution with copper(I) cyanide gives N-[4-cyano-2-(trifluoromethyl)phenyl]acetamide (3). Hydrolysis of the nitrile and the protecting group gives 4-amino-3-(trifluoromethyl)benzoic acid (4). Halogenation with chlorine then gives 4-amino-3-chloro-5-(trifluoromethyl)benzoic acid (5). Halogenation of the acid with thionyl chloride gives 4-amino-3-chloro-5-(trifluoromethyl)benzoylchloride (6). Treatment with diethyl malonate gives the acetophenone derivative 1-[4-amino-3-chloro-5-(trifluoromethyl)phenyl]ethanone (7). Halogenation with bromine in acetic acid leads to 1-[4-amino-3-chloro-5-(trifluoromethyl)phenyl]-2-bromoethanone (8). Treatment with tert-butylamine yields 1-[4-amino-3-chloro-5-(trifluoromethyl)phenyl]-2-(tert-butylamino)ethenone (9). Reduction of the ketone with sodium borohydride completes the synthesis of mabuterol (10).

See also Clenbuterol Cimaterol

References