Dexfenfluramine,Interneuron
Pharmaceuticals
(Lexington, Mass),
for Wyeth
Laboratories Inc
Appetite suppressant (systemic).
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in the treatment of obesity, but, like fenfluramine, was withdrawn wolrdwide following reports of valvular heart defects.
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).
Redux (Interneuron);Diomeride.
