Fexofenadine CAS 83799-24-0
Introduction：Basic information about Fexofenadine CAS 83799-24-0, including its chemical name, molecular formula, synonyms, physicochemical properties, and safety information, etc.
Fexofenadine Basic information
| Product Name: | Fexofenadine |
| Synonyms: | TERFENADINECARBOXYLATE;alpha-dimethyl-tyl)-alph;benzeneaceticacid,4-(1-hydroxy-4-(4-(hydroxydiphenylmethyl)-1-piperidinyl)bu;mdl16455;terfenadineacidmetabolite;2-(4-(1-HYDROXY-4-[4-(HYDROXY-DIPHENYL-METHYL)-PIPERIDIN-1-YL]-BUTYL)-PHENYL)-2-METHYL-PROPIONIC ACID;Fexofenadinebase;FEXOFENADINE(SUBJECTTOPATENTFREE) |
| CAS: | 83799-24-0 |
| MF: | C32H39NO4 |
| MW: | 501.66 |
| EINECS: | 801-893-7 |
| Product Categories: | API;Histamine receptor;Aromatics;Heterocycles;Metabolites & Impurities;Intermediates & Fine Chemicals;Metabolites;Pharmaceuticals;Active Pharmaceutical Ingredients |
| Mol File: | 83799-24-0.mol |
Fexofenadine Chemical Properties
| Melting point | 218-220°C |
| Boiling point | 697.3±55.0 °C(Predicted) |
| density | 1.171±0.06 g/cm3(Predicted) |
| storage temp. | Sealed in dry,Store in freezer, under -20°C |
| solubility | Methanol (Slightly, Heated, Sonicated) |
| form | Solid |
| pka | 4.43±0.10(Predicted) |
| color | White to Off-White |
| BCS Class | 1,3 |
| LogP | 2.81 |
| CAS DataBase Reference | 83799-24-0(CAS DataBase Reference) |
Safety Information
| Hazardous Substances Data | 83799-24-0(Hazardous Substances Data) |
| Description | Fexofenadine, the carboxylic acid metabolite of terfenadine, is widely available. Itaccounts for the antihistaminic properties of terfenadine, which is very rapidly metabolized viaCYP3A4-catalyzed processes. Members of the organic anion transporter protein family andthe drug efflux transporter P-glycoprotein are involved in the disposition of fexofenadine.Fexofenadine does not have the antiarrhythmic side effects of terfenadine. |
| Chemical Properties | White Powder |
| Originator | Alernex,Dabur Pharmaceuticals Ltd.,India |
| Uses | A metabolite of of terfenadine, a H1-Histamine receptor antagonist |
| Uses | The active metabolite of Terfenadine (T114500), a H1-histamine receptor antagonist. |
| Definition | ChEBI: A piperidine-based anti-histamine compound. |
| Manufacturing Process | Microbiological Preparation of Fexofenadine (Patent U.S. 6,558,931) Ten 250 ml Erlenmeyer flasks containing 100 ml of medium D are seeded withA. corymbifera LCP 63-1800. 50 mg of Terfenadine in 1 ml of ethanol is addedto each Erlenmeyer flask. The content of 10 Erlenmeyer flasks are filtered ongauze (the supernatant has a pH equal to 8.0), and saturation with sodiumchloride is carried out for 2 hours (pH = 5-6), followed by extracting 3 timeswith ethyl acetate and drying over magnesium sulfate. After evaporationunder reduced pressure, 409 mg of expected crude product is obtained (yield= 77%, approximately 90% pure product). This product is purified on acolumn of silica gel (230-400 mesh, 40 g of silica, diameter = 3 cm) elutingwith a methylene chloride/methanol/ammonium hydroxide mixture(82.5:15:2.5). 312 mg of pure Fexofenadine is recovered (61.4%). Synthesis of Fexofenadine (Patent U.S. No. 5,578,610 Aluminum chloride (44 g; 0.33 mol) was added in portions to a solution offreshly distilled 4-chlorobutyryl chloride (17 mL; 0.15 mol) in 460 mL ofcarbon disulfide at -10°C under a nitrogen atmosphere. The mixture wasstirred for 15 min, then the cooling bath was removed and the mixture wasallowed to warm to ambient temperature. The mixture was stirred then for 15min more, then cooled again to -10°C and a solution of ethyl-α,α-dimethylphenyl acetate (26.6 g; 0.14 mol) in 70 mL of carbon disulfide wasadded dropwise. The mixture was stirred for 3 hours, then stirred overnight atroom temperature. The reaction mixture was partitioned between water andCHCl3. The combined organic portions were dried over MgSO4, filtered andconcentrated in vacuo. The residue was dissolved in CH2Cl2 and filteredthrough a plug of SiO2, eluting with 10% EtOAc in hexane. Yield of ethyl 3-and 4-(4-chloro-1-oxobutyl)-α,α-dimethylphenylacetate 39.4 g (as a mixtureof aromatic regioisomers). To a solution of 39.4 g of ethyl 3- and 4-(4-chloro-1-oxobutyl)-α,α-dimethylphenylacetate dissolved in 800 mL of methanol and 200 mL of waterwas added 40 g of NaOH. The mixture was refluxed for one hour. The cooledmixture was then concentrated in vacuo. The concentrate was diluted withwater and washed with 2 portions of EtOAc. The aqueous layer was acidifiedwith concentrated HCl and extracted with 2 portions of EtOAc. The extractswere dried over MgSO4, filtered, and concentrated in vacuo to afford 30.3 g ofcrude product. The crude product was dissolved in 600 mL of EtOAc, 38 g ofcinchonidine was added, and the mixture was stirred overnight. The resultingsolids were filtered and washed with EtOAc and sucked dry under a rubberdam to afford 25 g of a solid 4-(cyclopropyl-oxo-methyl)-α,α-dimethylphenylacetic acid. A solution of 10.5 g of 4-(cyclopropyl-oxo-methyl)-α,α-dimethylphenylaceticacid in 250 mL of CH2Cl2 was cooled in an ice-MeOH bath and 25 g oftrimethylsilyliodide was then added via pipette. The mixture was stirred in theice bath for one hour, warmed to ambient temperature, and stirred for onehour. A solution of aqueous sodium bisulfite was then added and the mixturewas stirred well. The phases were partitioned and the aqueous layer wasextracted with CH2Cl2. The combined organics were washed with saturatedaqueous NaCl, dried over MgSO4, filtered, and concentrated in vacuo to afford12.6 g (77%) of 4-(4-iodo-1-oxobutyl)-α,α-dimethylphenylacetic acid. To a solution of 12.6 g of 4-(4-iodo-1-oxobutyl)-α,α-dimethylphenylacetic acidin 100 mL of ether cooled in an ice bath, was added 40 mL of ethereal CH2N2.The mixture was stirred at 0°C for few minutes, then let stand for 2 hours. Afew drops of AcOH were added to decompose excess CH2N2, then the mixturewas filtered and stripped to afford 12.6 g (96%) of methyl 4-(4-iodo-1-oxobutyl)-α,α-dimethylphenylacetate. A solution of 12.6 g of methyl 4-(4-iodo-1-oxobutyl)-α,α-dimethylphenylacetate in 500 mL of toluene in a one liter three neck flask wasadded 8.8 g of 4-(α,α-diphenyl)piperidinemethanol and 23 g of K2CO3 and themixture was refluxed for 7 hours. The cooled reaction mixture was thenfiltered and concentrated in vacuo. The residue was dissolved in ether andtreated with excess ethereal HCl. The mixture was then concentrated to asolid. The solid was treated with EtOAc and collected by filtration. The productwas then partitioned between EtOAc and 2 N Na2CO3. The organics were driedover MgSO4, filtered, and concentrated in vacuo to afford 13.5 g (79%) ofmethyl 4-[4-[4-(hydroxydiphenylmethyl)-1-piperidinyl]-1-oxobutyl]-α,α-dimethylphenylacetate. A solution of 13.5 g of methyl 4-[4-[4-(hydroxydiphenylmethyl)-1-piperidinyl]-1-oxobutyl]-α,α-dimethylphenylacetate in 250 mL of methanol was cooled inan ice-methanol bath and 1.8 g of NaBH4 was added in portions. After 1 hour,the mixture was concentrated to a solid. The residue was partitioned betweenEtOAc and saturated aqueous NaHCO3. The aqueous portion was extractedwith EtOAc. The combined organics were washed with saturated aqueousNaCl, dried over MgSO4, filtered, and concentrated in vacuo to afford 9.5 g(70%) of methyl 4-[4-[4-(hydroxydiphenylmethyl)-1-piperidinyl]-1-hydroxybutyl]-α,α-dimethylphenylacetate as a foam. To a solution of 9.5 g of methyl-4-[4-[4-(hydroxydiphenylmethyl)-1-piperidinyl]-1-hydroxybutyl]-α,α-dimethylphenylacetate in 300 mL of methanoland 150 mL of water was added 10 g of NaOH. The mixture was refluxed for 1hour, then cooled. The methanol was removed in vacuo. The concentrate wasdiluted with water and CHCl3 and the pH adjusted to approximately 5.5 to 6.0.The phases were separated and the aqueous phase was extracted with CHCl3.The combined organics were dried over MgSO4, filtered, and stripped to afford9.0 g of crude product. The crude product was dissolved in CH2Cl2 andchromatographed on Davisil Grade 633 SiO2 eluting with a gradient of CHCl3,to 10% of methanol in CHCl3, to 25% of methanol in CHCl3. The product wasconcentrated to afford 5.2 g of white crystals of 4-[4-[4-(hydroxydiphenylmethyl)-1-piperidinyl]-1-hydroxybutyl]-α,α-dimethylphenylacetic acid (Fexofenadine). In practice it is usually used as hydrochloride salt. |
| Therapeutic Function | Antihistaminic |
Fexofenadine Preparation Products And Raw materials
| Raw materials | Magnesium sulfate-->Nitrogen-->Sodium hydride-->Iodomethane-->Triphenylphosphine-->Pentane-->Methanesulfonyl chloride-->Trimethoxychlorosilane-->3-Butyn-1-ol-->Sodium borohydride-->Terfenadine-->4-Piperidinemethanol-->Aluminum chloride-->Iodotrimethylsilane |
| Preparation Products | FEXOFENADINE HYDROCHLORIDE |
