3703-76-2

Hustazol,Yoshitomi,Japan,1972

Cloperastine Hydrochloride (C587213) is an anti-tussive drug as an over-the-counter cold medicine.

ChEBI: 1-[2-[(4-chlorophenyl)-phenylmethoxy]ethyl]piperidine is a diarylmethane.

The manufacture of a related compound is first described. 28.1 parts of pchloro-benzhydryl bromide are heated to boiling, under reflux and with stirring, with 50 parts of ethylene chlorohydrin and 5.3 parts of calcined sodium carbonate. The reaction product is extracted with ether and the ethereal solution washed with water and dilute hydrochloric acid. The residue
from the solution in ether boils at 134° to 137°C under 0.2 mm pressure and is p-chloro-benzhydryl-(β-chloroethyl)ether.
28.1 parts of this ether are heated with 12 parts of methylethylamine (100%) in a sealed tube for 4 hours at 110°C. The product of the reaction is extracted several times with dilute hydrochloric acid, the acid solution made alkaline, in the cold, with concentrated caustic soda solution and the base which separates taken up in ether. The ether extract is washed with concentrated potassium carbonate solution, evaporated down, and the residue distilled in vacuo. The product is β-methylethyl aminoethyl p-chlorobenzhydryl ether, BP 152° to 153°C/0.1 mm.
Reaction with dimethylethylamine instead of methylethylamine leads directly to a quaternary compound, which type of compound can also be obtained by reacting the tertiary aminoethyl ether with reactive esters
If 18 parts of piperidine are used instead of 12 parts of methylethylamine then the same procedure results in the formation of p-chloro-benzyhydril-(β- piperidino-ethyl)ether, boiling at 178° to 180°C under 0.15 mm pressure.

Antitussive