- A fexofenadine and method for synthesizing intermediate
-
The invention relates to a simple and efficient synthetic method of fexofenadine (chemical name: 4-{1-hydroxyl-4-[4-(hydroxyl benzhydryl)-1-piperidyl]-butyl}-alpha, alpha-dimethyl-phenylacetic acid (I)) and its intermediate. According to the method, isopropyl benzene is used as a raw material. Through a Friedel-Crafts acylation reaction, a halogenation reaction and a carbonyl insertion reaction, a key intermediate 4-(4-chloro-1-butyryl)-alpha, alpha-dimethyl phenylacetic acid (IV) is obtained; the key intermediate reacts with another raw material dibenzyl-(4-pyridyl)-methanol (E) to obtain a key pyridinium intermediate 4-{4-chloro-[4-hydroxydiphenylmethyl]-1-pyridinium]-1-butyryl}-alpha, alpha-dimethyl phenylacetic acid (V); and through catalytic hydrogenation and metallic hydrogen reduction, high-purity fexofenadine is obtained. The synthetic method provided by the invention has advantages of smooth process, simple reaction, short route, convenient post-treatment, high yield and low cost, and is a very ideal preparation method of fexofenadine and industrialization feasible route.
- -
-
-
- POLYMORPHIC FORM OF FEXOFENADINE HYDROCHLORIDE, INTERMEDIATES AND PROCESS FOR ITS PREPARATION
-
The present invention relates to a novel polymorphic form of Fexofenadine hydrochloride, to a process for preparing it, to pharmaceutical compositions containing it, as well as its use. The invention also relates to intermediates useful for the preparation of Fexofenadine hydrochloride, antihistamine drug used in the treatment of allergy symptoms.
- -
-
-
- PROCESS FOR THE PREPARATION OF KETO INTERMEDIATES
-
Process for the preparation of 4-[1-oxo-4-[4-(hydroxyphenylmethyl)-1-piperidinyl]butyl]-α,α-dimethylbenzenacetic acid, which is an intermediate useful in the preparation of fexofenadine, by hydrating asymmetric alkynes.
- -
-
Page/Page column 3
(2010/09/17)
-
- Biooxidation of methyl group: application to the preparation of alcohol and acid metabolites of terfenadine, ebastine and analogues
-
The aim of this study was to found the best conditions to prepare metabolites of terfenadine, ebastine and analogues. For that purpose we investigated the structural substrate requirements needed for the oxidative whole cell activity and selected the most efficient conditions to obtain each compound. Our results showed that either alcohol or acid derivative arising from the oxidation of a methyl group is the main product, ratio depending on the microorganism used and on the culture conditions of cells. The oxidized metabolites were synthesized at preparative scale and isolated in 35-88% yield before characterization.
- El Ouarradi, Amane,Salard-Arnaud, Isabelle,Buisson, Didier
-
experimental part
p. 11738 - 11744
(2009/04/11)
-
- PROCESS FOR THE PREPARATION OF KETO COMPOUNDS
-
A process for the preparation of 4-[1-oxo-4-[4-(hydroxydiphenylmethyl)-1-piperidinyl]butyl]-α,α-dimethylbenzeneacetic acid, useful as an intermediate for the preparation of fexofenadine, is provided.
- -
-
Page/Page column 2-3
(2009/01/20)
-
- PROCESS FOR PREPARING FEXOFENADINE
-
A process for preparing fexofenadine is described, which provides for the hydrolysis of 4-[4-[4-(hydroxydiphenylmethyl)-l-piperidyl]-l-oxobutyl]-α,α- dimethylbenzeneacetic acid-alkyl ester, in a mixture of water and optionally an organic solvent, in the presence of a base; the carboxylate salt of 4- [4- [4- (hydroxydiphenylmethyl)- 1 -piperidyl] - 1 -oxobutyl] -α,α -dimethylbenzeneacetic acid is thus obtained, which is directly reduced as carboxylate in a basic environment with hydrogen in the presence of a suitable hydrogenation catalyst to give the carboxylate of fexofenadine, which is precipitated by neutralisation of the solution.
- -
-
Page/Page column 4; 5
(2008/06/13)
-
- PROCESS FOR PREPARING FEXOFENADINE
-
A process for preparing fexofenadine is described, comprising the purification of 4-[4-chloro-l-oxobutyl]-2,2-dimethylphenyl acetic acid alkyl ester by means of suspension in a hydrocarbon, preferably n-heptane. The compound thus obtained is dissolved in a suitable solvent and condensed with azacyclanol to give the compound shown below (I) where R is an alkyl radical, which is then hydrolysed and reduced to give fexofenadine.
- -
-
Page/Page column 5; 5-6
(2008/06/13)
-
- A process for the preparation of keto compounds
-
A process for the preparation of 4-[1-oxo-4-[4-(hydroxydiphenylmethyl)-1-piperidinyl]butyl]-α,α-dimethylbenzeneacetic acid, useful as an intermediate in the preparation of fexofenadine.
- -
-
Page/Page column 4-5
(2008/06/13)
-
- Process for the preparation of keto compounds
-
A process for the preparation of 4-[1-oxo-4-[4-(hydroxydiphenylmethyl)-1-piperidinyl]butyl]-α,α-dimethylbenzeneacetic acid, useful as an intermediate in the preparation of fexofenadine.
- -
-
Page/Page column 3
(2008/06/13)
-
- FEXOFENADINE POLYMORPHS AND PROCESSES OF PREPARING THE SAME
-
Anhydrous crystalline fexofenadine hydrochloride Form C, crystalline fexofenadine acetate monohydrate Form D, crystalline fexofenadine acetate dihydrate Form E and crystalline fexofenadine free base monohydrate Form F, processes of preparing the same, pharmaceutical compositions thereof, therapeutic uses thereof and methods of treatment therewith.
- -
-
Page/Page column 26-27
(2008/06/13)
-
- Process for production of piperidine derivatives
-
The present invention relates to a method for preparing piperidine derivative compounds by converting, with a piperidine compound, regioisomers having the formula: where Z is -CG1G2G3, and where m is an integer from 1 to 6; Q and Y are the same or different and are selected from the group consisting of O, S, and NR5; G1, G2, and G3 are the same or different and are selected from the group consisting of OR8, SR8, and NR8R9; and R5, R8, and R9 are the same or different and are selected from the group consisting of hydrogen, an alkyl moiety, and an aryl moiety.
- -
-
-
- PIPERIDINE DERIVATIVES
-
The present invention relates to substantially pure piperidine derivative compounds of the formulae: STR1 wherein R 1 is hydrogen or hydroxy;R 2 is hydrogen;or R 1 and R 2 taken together form a second bond between the carbon atoms bearing R 1 and R 2 ;R 3 is--COOH or--COOR 4 ;R 4 has 1 to 6 carbon atoms; A, B, and D are the substituents of their respective rings each of which may be different or the same and are hydrogen, halogens, alkyl, hydroxy, alkoxy, or other substituents. A process of preparing such piperidine derivative compounds in substantially pure form is also disclosed.
- -
-
-
- Piperidine derivatives
-
Pharmaceutically useful compounds of the following formula: STR1 wherein R1 represents hydrogen or hydroxy; R2 represents hydrogen; or R1 and R2 taken together form a second bond between the carbon atoms bearing R1 and R2 ; n is a positive whole integer of from 1 to 5; R3 is --CH3, --CH2 OH, --COOH or --COOalkyl wherein the alkyl moiety has from 1 to 6 carbon atoms and is straight or branched; and A and B are individually hydrogen or hydroxy; with the provisos that at least one of A or B is hydrogen and one of A or B is other than hydrogen when R3 is --CH3 ; and pharmaceutically acceptable acid addition salts thereof.
- -
-
-
