TRIMETHOBENZAMIDE HYDROCHLORIDE

Tigan,Beecham,US,1973

antiemetic

Trimethobenzamide Hydrochloride a pharmaceutical compound used in the prevention of nausea and vomiting in patients. Also used in the treatment of Parkinson’s disease.

To 122 grams (1 mol) of p-hydroxybenzaldehyde in 1 liter of chlorobenzene were added 66 grams (1.04 mols) of sodium methoxide (85%) and 108 grams (1 mol) of 2-dimethylaminoethyl chloride. The mixture was stirred and refluxed for 15 hours, then cooled and the precipitated sodium chloride filtered off. The filtrate was concentrated at steam temperature under water vacuum and the residual oil was fractionated in high vacuum, to give 4-(2- dimethylaminoethoxy)benzaldehyde, BP2.2145°C.
Two teaspoons of Raney nickel catalyst were added to a solution of 65.6 grams (0.34 mol) of 4-(2-dimethylaminoethoxy)benzaldehyde in 300 ml of 10% ammoniacal ethanol. The mixture was hydrogenated at 80°C and a pressure of 1,000 psi. The catalyst was filtered off, the volatiles were distilled off and the residual oil was fractionated in high vacuum, to obtain 4-(2- dimethylaminoethoxy)benzylamine, BP0.3120° to 123°C.
To 9.7 grams (0.05 mol) of 4-(2-dimethylaminoethoxy)benzylamine, dissolved in 100 ml of acetonitrile, was added all at once 12 grams (0.051 mol) of 3,4,5-trimethoxybenzoyl chloride, dissolved in 75 ml of acetonitrile. The mixture was stirred and refluxed for 8 hours, and then cooled. The crystalline solid, which had formed, was filtered off, washed with acetonitrile and recrystallized from acetonitrile, to give 4-(2-dimethylaminoethoxy)-N-(3,4,5- trimethoxybenzoyl)benzylamine hydrochloride, MP 185° to 186°C.

Tigan (King).

Antinauseant