p-chloro-alpha-[2-(dimethylamino)-1-methylethyl]-alpha-methylphenethyl alcohol hydrochloride

Silomat,Boehringer Ingelheim,Switz.,1960

Clobutinol Hydrochloride is a non-narcotic antitussive drug useful for treatment of acute respiratory diseases.

ChEBI: Clobutinol hydrochloride is a member of benzenes and an organic amino compound.

A solution of 0.2 mol (33 g) of 3-methyl-4-dimethylamino-butanone-(2) [produced according to Mannich, Arch. Pharm., vol. 265, page 589 (1927)] in 50 cc absolute ether was added dropwise, while stirring and cooling with ice, to a Grignard solution of 0.4 mol p-chlorobenzylmagnesium-chloride which was produced from 64.5 g p-chlorobenzyl-chloride and 9.8 g magnesium in 200 cc absolute ether. The reaction product was heated for an additional onehalf hour under reflux to bring the reaction to completion, and thereafter the reaction mixture was decomposed into an ether phase and an aqueous phase with about 50 cc concentrated hydrochloric acid and about 200 g ice. The ether phase was discarded and the aqueous phase was adjusted to an alkaline pH with ammonia and then thoroughly extracted with ether. After concentrating the united, dried ether extract solutions, the oily residue was fractionally distilled. The reaction product was obtained in the form of a colorless oil having a boiling point of 179° to 181°C. The yield was 48.5 g corresponding to 95% of theory.
The hydrochloride addition salt of the above reaction product was prepared in customary fashion, that is, by reaction with hydrochloric acid, followed by fractional crystallization from a mixture of alcohol and ether. The two possible racemic forms were obtained thereby. The difficultly soluble racemate had a melting point of 169° to 170°C and the more readily soluble racemate had a boiling point of 145° to 148°C.

Antitussive