Fifty grams of d-desoxyephedrine hydrochloride was dissolved in a small
amount of water and a molar excess of sodium hydroxide was .added thereto.
The resulting forty grams of precipitated oily d-desoxyephedrine was collected
in ether and the whole was thereafter dried with anhydrous potassium
carbonate. The ether was then removed, the resulting oily residue having an
nD22 of 1.5045 was stirred in a flask with 40 grams of anhydrous sodium
carbonate at 120°C, and 34.6 grams of benzyl chloride was added dropwise
thereto over a period of thirty minutes. Stirring was continued for 2 hours,
whereafter the reaction mixture was extracted with benzene.
The benzene was distilled from the extract and the residue of d-N-methyl-Nbenzyl-β-phenylisopropylamine was distilled at reduced pressure. The thus
obtained free base, distilling at 127°C at a pressure of 0.2 mm of mercury
and having an nD19 of 1.5515, was dissolved in ethyl acetate and a molar
equivalent of ethanolic hydrogen chloride was added thereto. Anhydrous ether
was added to the mixture and d-N-methyl-N-benzyl-β-phenylisopropylamine
hydrochloride precipitated from the reaction mixture as an oil which was
crystallized from ethyl acetate to give crystals melting at 129° to 130°C.
Didrex (Pharmacia &
Upjohn).
Benzphetamine hydrochloride, (+)-N-benzyl-N, -dimethylphenethylaminehydrochloride, (+)-1-phenyl-2-(Nmethyl-N-benzylamine)propane hydrochloride (Didrex), isN-benzyl–substituted methamphetamine. The large (benzyl)N-substituent decreases excitatory properties, in keepingwith the general structure–activity relationship (SAR) forthe group. Anorexiant properties are retained. Classically,amphetamine-like drugs with larger than N-methyl substituentsare cited as anorexiant through central β-agonism.No claims for selectivity among β-receptor subtypes havebeen made in such citations. The compound shares mechanism-of-action characteristics with methylphenidate.Overall, it is said to reduce appetite with fewer CNS excitatoryeffects than dextroamphetamine.
