PHENDIMETRAZINE BITARTRATE

Originator

Plegine, Ayerst, US ,1961

Uses

Appetite suppressant (systemic).

Manufacturing Process

A mixture of 61 grams 1-phenyl-1-oxo-2-(N-methyl-N-ethanolamino)-propane hydrochloride and 100 cc 98-100% formic acid was refluxed at the boiling point at atmospheric pressure for 45 minutes on an oil bath. Thereafter, the oil bath temperature was increased to 180°C and as much of the excess unreacted formic acid as possible was distilled off. A vigorous evolution of carbon dioxide developed during the distillation, which ceased after approximately 45 additional minutes. The honey-yellow syrup which remained as the distillation residue was worked up by admixing it with about six volumes of water and adjusting the aqueous mixture to alkaline reaction with concentrated sodium hydroxide. An oily phase separated out which was extracted with ether. The ether extract was washed with water and dried over potassium carbonate. The solvent was distilled off and the distillation residue was fractionally distilled in vacuo. The base boils at 132°-133°C at 12 mm. The yield was 93% of theory. Reaction with tartaric acid gave the final product.
The starting material is produced by reacting propiophenone with bromine and then reacting the α-bromopropiophenone produced with 2methylaminomethanol.

brand name

Bontril (Mallinckrodt); Bontril (Valeant); Melfiat (Numark).

Therapeutic Function

Antiobesity

General Description

The optically pure compound phendimetrazine tartrate,(2S,3S)-3,4-dimethyl-2-phenylmorpholine-L-(+)-tartrate(Plegine), is considered an effective anorexiant that is lessabuse prone than amphetamine. The stereochemistry of(+)phendimetrazine is as shown.

Safety Profile

Poison by ingestion, intraperitoneal, subcutaneous, and intravenous routes. An antihistamine. When heated to decomposition it emits toxic fumes of NOx.