(+)-FENFLURAMINE HYDROCHLORIDE Property

alpha 

D25 +9.5° (c = 8 in ethanol)

Boiling point:

108-112 °C(Press: 12 Torr)

Density 

1.078±0.06 g/cm3(Predicted)

pka

10.23±0.19(Predicted)

Safety

Hazard Codes 

T

Risk Statements 

23/24/25

Safety Statements 

22-36/37/39-45

RIDADR 

UN 2811 6.1/PG 3

WGK Germany 

3

RTECS 

SH6824000

Hazardous Substances Data

3239-44-9(Hazardous Substances Data)

Toxicity

LD50 orally in rats: 114.6 mg/kg (Le Douarec)

Hazard and Precautionary Statements (GHS)

(+)-FENFLURAMINE HYDROCHLORIDE Chemical Properties,Usage,Production

Originator

Dexfenfluramine,Interneuron Pharmaceuticals (Lexington, Mass), for Wyeth Laboratories Inc

Uses

Appetite suppressant (systemic).

Definition

ChEBI: The S-enantiomer of fenfluramine. It stimulates the release of serotonin and selectively inhibits its reuptake, but unlike fenfluramine it does not possess catecholamine agonist activity. It was formerly given by mouth as the hydrochloride in the treatment of obesity, but, like fenfluramine, was withdrawn wolrdwide following reports of valvular heart defects.

Manufacturing Process

To 10.65 parts acetic anhydride there were added, with cooling, 8 parts 1-(3- trifluoromethylphenyl)-2-aminopropane and 100 parts water. The mixture was neutralized with 30 parts sodium carbonate. The organic layer was extracted twice with 50 parts ether. The ether solutions were washed with 25 parts water and dried over potassium carbonate. On distillation there were obtained 9 parts 1-(3-trifluoromethylphenyl)-2-acetyl-aminopropane. 9 parts of it were reduced in solution in 100 parts ether with 1.7 parts lithium and aluminium hydride with 20 parts ether. The suspension was refluxed for 4 hours, hydrolysed with 2 parts water, 2 parts 4 N sodium hydroxide and then 6 parts water. The precipitate was drained washed with 50 parts ether, the filtrate was extracted twice with 50 parts 0.5 N sulfuric acid. The acidic layers were separated by sedimentation and neutralized with 100 parts 4 N sodium hydroxide, the separated amine was extracted with 200 parts ether. There were obtained 6 parts 1-(3-trifluoromethylphenyl)-2-ethylaminopropane (boiling point 108°-112°C at 12 mm). The hydrochloride thereof was recrystallized from mixture of ethyl alcohol and ether (melting point 166°C).
S-Isomer was prepared the next way. To a solution of 160 parts of dibenzoyl d-tartaric acid in 1600 parts of anhydrous ethanol were added for 15 minutes 80 parts of dl-1-(3-trifluoromethylphenyl)-2-ethylaminopropane. After 15 additional minutes, 90.5 parts of crystalline solid were isolated. When this product was recrystallized from 1300 parts of anhydrous ethanol, there was obtained 70 parts of dibenzoyl d-tartarate acid salt of L-1-(3- trifluoromethylphenyl)-2-ethylaminopropane. This salt was treated with 500 parts of 4 N NaOH. The mixture was extracted with 2x200-part portions of diethyl ether and the ether extract was re-extracted with 100 parts of 4 N hydrodiboric acid. After treatment with 120 parts of 4 N NaOH, the free amine amounting to 25 parts distills at 105°-107°C (17.5 mm.). [α]D25: - 9.6° (c=8% in ethanol).

brand name

Redux (Interneuron);Diomeride.

Therapeutic Function

Antiobesity