Grignard reaction of 3-trifluoromethylbenzene-magnesium bromide (II) with 3-pyridinecarboxaldehyde (I) in THF at 15 C gives alpha-[3-(trifluoromethyl)phenyl]-3-pyridinemethanol (III). Oxidation of this compound with MnO2 in refluxing CH2Cl2 yields the corresponding ketone (IV). The oximation reaction carried out with NH2OH.HCl in isopropanol-HCl at 70 C affords (3-pyridinyl)-[3-(trifluoromethyl)phenyl]methanone oxime (V) (more than 90% of the E-isomer). The alkylation of (V) with ethyl bromovalerate in the presence of NaOH in DMF produces ethyl 5-[[[(3-pyridinyl)[3-(trifluoromethyl)phenyl]methylene]amino]oxy] pentanoate (VI). Hydrolysis of the ester with aqueous NaOH followed by HCl treatment gives, after recrystallization from diisopropylether, ridogrel.

Grignard reaction of 3-trifluoromethylbenzene-magnesium bromide (II) with 3-pyridinecarboxaldehyde (I) in THF at 15 C gives alpha-[3-(trifluoromethyl)phenyl]-3-pyridinemethanol (III). Oxidation of this compound with MnO2 in refluxing CH2Cl2 yields the corresponding ketone (IV). The oximation reaction carried out with NH2OH.HCl in isopropanol-HCl at 70 C affords (3-pyridinyl)-[3-(trifluoromethyl)phenyl]methanone oxime (V) (more than 90% of the E-isomer). The alkylation of (V) with ethyl bromovalerate in the presence of NaOH in DMF produces ethyl 5-[[[(3-pyridinyl)[3-(trifluoromethyl)phenyl]methylene]amino]oxy] pentanoate (VI). Hydrolysis of the ester with aqueous NaOH followed by HCl treatment gives, after recrystallization from diisopropylether, ridogrel.