N-[3-chloro-2-[[methyl[2-morpholino-2-oxoethyl]amino]methyl]phenyl]benzamide monohydrochloride

Originator

Noleptan,Thomae,W. Germany,1973

Definition

ChEBI: Fominoben hydrochloride is a member of benzamides.

Manufacturing Process

(a) A mixture consisting of 9.75 g of 6-chloro-2-dibenzoylamino-benzyl bromide, 2.34 g of sarcosine methyl ester, 3.18 ml of triethylamine and 250 ml of chloroform was refluxed for five hours. Thereafter, an addition 0.5 g of sarcosine methyl ester was added, and the mixture was again refluxed for five hours. Subsequently, the chloroform was evaporated in vacuo, the residue was taken up in ethylacetate, the insoluble matter was separated by filtration, and the filtrate was again evaporated in vacuo. The residual oil was dissolved in methanol, the solution was admixed with 25 ml of 2 N sodium hydroxide, and the mixture was allowed to stand overnight at about 20°C. Thereafter, the methanol was evaporated in vacuo, and the residual aqueous solution was adjusted to pH 2 with 2 N hydrochloric acid, then extracted with ethyl acetate and then adjusted to pH 6 with 2N sodium hydroxide. The crystalline product precipitated thereby was collected by vacuum filtration and recrystallized from water, yielding N-(2-benzoylamino-6-chloro-benzyl)-N-methyl-glycine, MP 150°C to 152°C.
(b) 80.7 g of N-(2-benzoylamino-6-chlorobenzyl)-N-methyl-glycine and 38 ml of triethylamine were dissolved in 1 liter of dry chloroform. While stirring the resulting solution at -15°C to -5°C, 23.4 ml of ethyl chloroformate were rapidly added dropwise, and the mixture was stirred for 40 minutes more at - 15°C to -5°C. Thereafter, 50 ml of morpholine were added all at once, and the mixture was allowed to stand at 20°C for 20 hours. Subsequently, the chloroformic reaction solution was washed three times with brine, dried over magnesium sulfate and evaporated in vacuo, and the oily residue was taken up in ether, whereupon it crystallized. The crystalline product was recrystallized from methanol, yielding N-(2-benzoyl-amino-6-chloro-benzyl)-Nmethyl-glycine-morpholide, MP 122.5°C to 123°C.
The product was dissolved in isopropanol, and the solution was acidified with anhydrous hydrochloric acid, yielding the hydrochloride, MP 206°C to 208°C (decomp.).

Therapeutic Function

Antitussive, Respiratory stimulant Fominoben hydrochloride