floctafenine

floctafenine Basic information
Product Name:floctafenine
Synonyms:Anthranilic acid, N-[8-(trifluoromethyl)-4-quinolyl]-, 2,3-dihydroxypropyl ester (8CI);Benzoic acid, 2-[[8-(trifluoromethyl)-4-quinolinyl]amino]-, 2,3-dihydroxypropyl ester;Diralgan;Floctafenin;Glycerol, 1-[N-[8-(trifluoromethyl)-4-quinolyl]anthranilate] (8CI);Idalon;Idarac;Novodolan
CAS:23779-99-9
MF:C20H17F3N2O4
MW:406.36
EINECS:245-881-4
Product Categories:Amines;Aromatics;Intermediates & Fine Chemicals;Pharmaceuticals
Mol File:23779-99-9.mol
floctafenine Structure
floctafenine Chemical Properties
Melting point 179-180°
Boiling point 592.1±50.0 °C(Predicted)
density 1.3473 (estimate)
storage temp. 2-8°C
solubility DMSO (Slightly), Methanol (Slightly)
form Solid
pka13.07±0.20(Predicted)
color Off-White to Pale Beige
Safety Information
ToxicityLD50 in male mice, rats (mg/kg): 3400, 960 orally; 180, 160 i.v. (Glomot)
MSDS Information
floctafenine Usage And Synthesis
OriginatorIdarac,Diamant,France,1976
UsesFloctafenine is an nonsteroidal antiinflammatory drug (NSAID) used in inflammatory disorders.
DefinitionChEBI: Floctafenine is an organic molecular entity.
Manufacturing ProcessStep A: Ortho-Trifluoromethylanilinomethylene Ethyl Malonate - A mixture of 54.8 grams of ortho-trifluoromethylaniline and 73.5 grams of ethoxymethylene ethyl malonate was heated to 120°C under an inert atmosphere and maintained for 1 hour at this temperature while distilling off the ethanol formed. The mixture was cooled and the elimination of ethanol was completed by distillation under reduced pressure. The mixture was cooled to obtain 115 grams of ortho-trifluoromethylanilinomethylene ethyl malonate which was used as is for the following stage. A sample of the product was crystallized from petroleum ether (BP = 65° to 75°C) to obtain a melting point of 94°C.
Step B: 3-Carbethoxy-4-Hydroxy-8-Trifluoromethylquinoline - A mixture of 113 grams of crude ortho-trifluoromethylanilinomethylene ethyl malonate from Step A, and 115 cc of phenyl oxide was heated rapidly under an inert atmosphere. At about 195°C, the ethanol formed began to distill off. At the end of about 30 minutes, the interior temperature reached 250°C and the reaction mixture was heated to reflux. Reflux was maintained for 1 hour and the mixture was then cooled, 25 cc of acetone were added and the mixture was allowed to crystallize. The mixture was filtered and the crystals thus formed were washed and dried to obtain 71.5 grams of 3-carbethoxy-4- hydroxy-8-trifluoromethylquinoline with a melting point of 210° to 214°C, which was used as is for the following stage. A sample of this product was crystallized from ethanol to show a melting point of 216°C.
Step C: 3-Carboxy-4-Hydroxy-8-Trifluoromethylquinoline - 70 grams of crude 3-carbethoxy-4-hydroxy-8-trifluoromethylquinoline, obtained in Step B, were introduced under an inert atmosphere into a mixture of 300 cc of water and 100 cc of aqueous 10 N solution of sodium hydroxide. The reaction mixture was heated to reflux and maintained there for 2 hours and forty-five minutes. The solution obtained was poured over a mixture of water, ice and 100 cc of aqueous 11.8 N solution of hydrochloric acid. The precipitate thus formed was isolated by filtration, washed with water and introduced into a solution of 20 grams of sodium bicarbonate in 2 liters of water.
The mixture was heated to 90°C and filtered to remove slight persisting insolubles. The filtrate was acidified with acetic acid to bring the pH to about 5.5 and the precipitate formed was isolated by filtration, washed and dried to obtain 58 grams of 3-carboxy-4-hydroxy-8-trifluoromethylquinoline having amelting point of 290° to 292°C, which was used as is for the following stage. A sample of the product was crystallized from hot and cold acetone, treated with charcoal to obtain pure 3-carboxy-4-hydroxy-8-trifluoromethylquinoline having a melting point of 292°C.
Step D: 4-Hydroxy-8-Trifluoromethylquinoline - Under an inert atmosphere, 56.5 grams of crude 3-carboxy-4-hydroxy-8-trifluoromethylquinoline, obtained in Step C were introduced into 110 cc of phenyl oxide. The reaction mixture was rapidly heated to reflux and maintained at reflux for an hour and fifteen minutes. The reaction mixture was cooled to about 50°C and 20 cc of isopropyl ether were added thereto. The mixture was cooled to 20°C and allowed to crystallize. The precipitate formed was isolated by filtration, washed and dried to obtain 45.8 grams of 4-hydroxy-8- trifluoromethylquinoline having a melting point of 180°C. A sample of this product was crystallized from acetone, treated with charcoal to obtain pure 4- hydroxy-8-trifluoromethylquinoline having a melting point of 180°C.
Step E: 4-Chloro-8-Trifluoromethylquinoline - 44.3 grams of crude 4-hydroxy- 8-trifluoromethylquinoline obtained in Step D were introduced in small amounts into 130 cc of phosphorus oxychloride and then the reaction mixture was held for 15 minutes at ambient temperature and heated to reflux and maintained at reflux for 1hour. The mixture was cooled and excess phosphorus oxychloride was removed by distillation under reduced pressure. Water, ice, and then 80 cc of aqueous solution of ammonia at 22°Be were added to the residue and the mixture was stirred and the aqueous phase was extracted with ether. The ethereal extracts were washed with a dilute aqueous solution of ammonia, then with water, dried, treated with charcoal and concentrated to dryness to obtain 45.4 grams of 4-chloro-8- trifluoromethylquinoline having a melting point of 78°C, which was used as is for the preparation of 4-(ortho-methoxycarbonylphenylamino)-8- trifluoromethylquinoline. A sample of crude 4-chloro-8-trifluoromethylquinoline was crystallized from petroleum ether (BP = 65° to 75°C) to get a product with a melting point of 78°C.





Brand nameIdarac (Hoechst-Roussel);Tambocor.
Therapeutic FunctionAnalgesic
floctafenine Anthranilic acid

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