Dibutoline

Originator

Dibuline Sulfate,MSD ,US,1952

Manufacturing Process

About 55.5 g of β-chloroethyl-di-n-butylcarbamate and about 22.6 g of dimethylamine are placed in a container, firmly sealed, and heated at about 95°C for about 16 hours. To the resulting crude mixture is added ethyl ether and the mixture filtered to remove dimethylamine hydrochloride formed during the course of the reaction. The ethereal solution is then extracted with 12 N hydrochloric acid. Under a fresh layer of ether and at a temperature under 10°C the aqueous acid extract is first neutralized with sodium carbonate and then made strongly alkaline with sodium hydroxide. The supernatant ethereal solution is then separated and dried over potassium hydroxide. The ethereal solution is finally concentrated and the residue obtained is fractionally distilled under vacuum. The β-dimethylaminoethyl-di-n-butylcarbamate is found to distill undecomposed at about 128°C to 130°C under approximately 2 mm pressure.
A mixture of about 100 g of β-dimethylaminoethyl-di-n-butylcarbamate and about 188 cc of ethyl iodide is held at about 25°C for two hours. The temperature is kept about 25°C by occasional cooling in an ice bath during the first half hour. About 1,600 cc of anhydrous ethyl ether is then added causing the precipitation of a dense white product. After standing for about 16 hours at 0°C the product is filtered off, washed thoroughly with anhydrous ether, and dried under diminished pressure at room temperature over sulfuric acid. The β-(dimethyl ethyl ammonium iodide)-ethyl-di-n-butylcarbamate thus obtained is a white crystalline powder, slightly hygroscopic with a melting point of about 76°C to 77°C.
A mixture of about 150 g of β-(dimethyl ethyl ammonium iodide)-ethyl-di-nbutylcarbamate, 90 g of silver sulfate, 750 cc of water and 750 cc of ethanol is stirred at about 30°C for approximately 45 minutes. The silver iodide formed is removed and the excess silver remaining in solution is removed by bubbling in hydrogen sulfide for five minutes followed by filtration to remove the precipitated silver sulfide. The filtrate is concentrated to a thick syrup under vacuum and about one liter of benzene is added which is distilled off with stirring to atmospheric pressure to remove the last traces of water. The residual benzene is removed under vacuum and the product granulated by stirring with one liter of anhydrous ether for two hours. The product is removed, washed with anhydrous ether, and dried under diminished pressure over phosphorous pentoxide at 25°C. The β-(dimethyl ethyl ammonium sulfate)-ethyl-di-n-butylcarbamate thus obtained is a very hygroscopic white solid having a melting point of about 166°C with decomposition.

Therapeutic Function

Anticholinergic (ophthalmic)