TITLE OF THE INVENTION:
IMPROVED PROCESSES FOR HIGHLY PURE FEXOFENADINE HYDROCHLORIDE & ITS INTERMEDIATES.
FIELD OF INVENTION:
The present invention, in general, relates to the field of chemical synthesis of H2 receptor antagonist and more particularly, the present invention provides an improved process for the preparation & purification of key intermediates of Fexofenadine namely Methyl 2-[4-(4-chlorobutyryl]-2-methylpropanoate (compound of formula II) and a,a-Dimethyl-4-[l-oxo-4-[4-(hydroxydiphenylmethyl)-l-piperidinyl]butyl]phenyl methyl acetate (compound of Formula IV) via a new intermediate of compound of formula III.
The present invention also relates to the purification process for Fexofenadine base (V) as well as Fexofenadine hydrochloride (VI) for generation of highly pure i.e. almost impurity free Fexofenadine hydrochloride of formula VI.
BACKGROUD OF INVENTION:
Fexofenadine hydrochloride of Formula VI, is a non-sedative antihistaminic compound and is chemically known as, a,a-Dimethyl-4-[l-hydroxy-4-[4-(hydroxydiphenylmethyl)-l-piperidinyl]butyl] Benzene acetic acid hydrochloride.
It is reported to be a specific H2-receptor antagonist that is also devoid of any ant cholinergic, antiseroloninergic, and ant adrenergic effects.

Fexofenadine was first disclosed in US Patent 4,284,129. According to the said patent fexofenadine can be prepared by reacting ethyl [a,a]-dimethylphenyl acetate and 4-chlorobutyryl chloride under Friedal Crafts conditions, to give compound of formula 11 (meta isomer ~35%) which on condensation with [a,a]-diphenyl-4-piperidinemethanol gives compound of formula IV, followed by reduction & hydrolysis yield Fexofenadine base (compound V). As the compound of formula II produced by this process is having ~35% of meta isomer, which is not possible to remove at this stage. Therefore, an improved process for the preparation/purification of compound of formula II was required. Similarly, there was a need of cost effective process for the preparation as well as purification of compound of formula IV to improve its quality especially removal of meta isomer at commercial scale as per market demand.
Similarly the methods reported in prior art for the preparation of fexofenadine involves the reduction & hydrolysis of compound of formula IV to give compound of formula V. Generally reduction reaction is carried out at ambient temperature and always results in keto fexofenadine impurity of formula VII in the final API due to unreacted compound of formula IV.
In the patents such as WO 95/31437, US 2004/0077683, WO 2005/67511, preparation of Fexofenadine is reported.
Most of the processes described above are not suitable to get high purity of Fexofenadine hydrochloride at commercial scale due to higher contents of impurities specially keto Fexofenadine, meta keto Fexofenadine & meta-Fexofenadine impurities. Therefore, to achieve highly pure API at commercial scale, an improved process was required to reduce/remove all these impurities. Furthermore, as keto Fexofenadine & meta

keto Fexofenadine do not get separated by pharmacopoeal analytical method for HPLC analysis, therefore, there was an urgent need of an improved analytical HPLC method by which both these impurities can be separated along with simultaneous separation of other impurities including meta fexofenadine by single method.
SUMMARY OF INVENTION:
According to the present invention, a new purification process for intermediate of formula II for removal of meta isomer by preparation of new amine salt intermediate of formula III.
Other objective of the present invention is to develop a novel cost effective process for preparation & purification of compound of formula II to reduce the impurities especially meta isomer to get high purity of compound IV at commercial scale for industrial use. The present invention also describes the purification process for Fexofenadine hydrochloride for removal of impurities specially Keto Fexofenadine, meta keto Fexofenadine & meta Fexofenadine impurities.
BRIEF DESCRIPTION OF THE DRAWINGS
A better understanding of the features and advantages of the present invention will be obtained by reference to the following detailed description that sets forth illustrative embodiments, in which the principles of the invention are utilized, and the accompanying drawings of which:
Figure 1 gives the route of synthesis being followed for the preparation of Fexofenadine hydrochloride & its intermediates in highly pure form.
Figure 2 is FTIR OF LORATADINE POLYMORPHIC FORM I

DETAILED DESCRIPTION OF THE INVENTION:
The first aspect of the present invention is to provide highly pure compound of formula II by removal of the meta isomer. It ultimately results in controlling the meta isomer in the final API.
According to second aspect of the present invention a process for highly pure compound of formula II which comprises:
a) treatment of crude compound of formula II (meta isomer ~35%) with caustic in an aliphatic alcohol followed by pH adjustment to 1.0 - 2.0 using hydrochloric acid,
b) extraction of product in an organic solvent,
c) adding an organic amine,
d) isolating compound of formula III i.e. 2-methyl-2-[4-(4-chlorobutanoyl) phenyl propanoic acid amine salt by adding aliphatic hydrocarbon as anti-solvent,
e) treatment of compound of formula III of step (d) with hydrochloric acid in an organic solvent to get pH 1.0-2.0,
f) Recovery of solvent by conventional methods to get residue,
g) Reaction of residue of step (f) with Methanolic hydrogen chloride gas,
h) Isolation of pure compound of formula II i.e. 2-methyl-2-[4-(4-chlorobutanoyl) phenyl propanoate by extraction in suitable organic solvent followed by its recovery by conventional methods.

According to another aspect of the present invention, aliphatic alcohols used in step are methanol, ethanol, propanol, butanol or a mixture thereof.
According to yet another aspect of the invention, the organic solvents used in step (b) are aliphatic halogenated hydrocarbon such as Methylene chloride, chloroform, carbon tetra chloride etc, aromatic hydrocarbons such as toluene, xylene, benzene etc, aliohatic esters such as ethyl acetate, propyl acetate etc or a mixture thereof
According to still another aspect of the invention, the organic amine used in step ( c) is selected from dicyclohexylamine, benzylamine, phenylhydrazine, a,a-Diphenyl-4-piperidinemethanol, 2-(2-methoxyphenoxy) ethyl amine, tris(hydroxymethyl)aminomethane, cyclohexylamine, dibenzylamine, phenyl ethyl amine, di-n-propyl amine, diisopropyl amine, t-butyl amine, isopropyl amine and a-methyl benzyl amine, 4-methoxy aniline.
According to another aspect of the invention, the anti-solvent used in step (d) is selected from C5-C8 aliphatic hydrocarbon such as pentane, hexane, heptane, octane and a mixture thereof
According to a new aspect of the present invention, novel compounds of formula III were prepared.
According to another aspect of the invention, the organic solvent used in step (e) is selected from aliphatic halogenated hydrocarbon such as Methylene chloride, chloroform, carbon tetra chloride etc, aromatic hydrocarbons such as toluene, xylene, benzene etc, aliphatic esters such as ethyl acetate, propyl acetate etc or a mixture thereof.
According to yet another aspect of the invention, reaction temperature in step (g) is 20-40 °C.

According to another aspect of the invention, the organic solvent used in step (h) is selected from aliphatic halogenated hydrocarbon such as Methylene chloride, chloroform, carbon tetra chloride etc, aromatic hydrocarbons such as toluene, xylene, benzene etc, aliphatic esters such as ethyl acetate, propyl acetate etc, aliphatic ketones such as acetone, methyl isobutyl ketone etc or a mixture thereof.
According to third aspect of the present invention a process for highly pure compound of formula IV which comprises:
(i). reaction of pure compound of formula II (meta isomer <1%) with azacyclonol in a mixture of aliphatic ketone & water in presence of an inorganic base,
(ii). complete recovery of solvent at reduced pressure,
(iii). adding aliphatic alcohol and isolating the material by conventional methods like filtration/centrifugation,
(iv). dissolving compound of step (iii) in an organic solvent followed by carbon treatment,
(v). crystallization of product by cooling,
(vi). isolating pure compound of formula IV by filtration/centrifugation followed by drying.
According to one aspect of the present invention, aliphatic ketone used in step (i) acetone, methyl ethyl ketone, methyl isobutyl ketone or a mixture thereof
According to another aspect of the invention, the inorganic base used in step (i) is selected from sodium carbonate, potassium bicarbonate, sodium bicarbonate, potassium bicarbonate or a mixture thereof

According to yet another aspect of the invention, the recovery of solvent in step (ii) is done at a temperature <60 °C at reduced pressure.
According to still another aspect of the invention, the aliphatic alcohol used in step (iii) for isolation is selected from methanol, ethanol, propanol, butanol and/or a mixture thereof
According to yet another aspect of the present invention, organic solvents used in step (iv) is selected from aliphatic halogenated/non-halogenated hydrocarbon such as Methylene chloride, chloroform, carbon tetra chloride, hexane, heptane etc, aromatic hydrocarbons such as toluene, xylene, benzene etc, aliphatic esters such as ethyl acetate, propyl acetate etc, aliphatic alcohol such as methanol, ethanol, propanol, butanol, aliphatic ketones such as acetone, methyl ethyl ketone, methyl isobutyl ketone or a mixture thereof.
According to yet another aspect of the invention, the temperature for crystallization of product in step (v) is 0-40 °C, most preferably 0-5 °C.
According to another aspect of the invention, the drying temperature in step (vi) is 40-80 °C, most preferably 40-50 °C.
According to fourth aspect of the present invention, a process for highly pure compound of formula V i.e. Fexofenadine base was developed which comprises:
(i) dissolving compound of formula V in aliphatic alcohol & aliphatic amide to get clear solution,
(ii) cooling the clear solution for crystallization of the product,
(iii) isolating pure compound of formula V by filtration and drying.

According to one aspect of the invention, the aliphatic alcohol used in step (i) is selected from methanol, ethanol, propanol, butanol and/or a mixture thereof.
According to another aspect of the invention, the aliphatic amide used in step (i) is selected from N,N-dimethylformamide, N,N-dimethylacetamide and/or a mixture thereof.
According to yet another aspect of the invention, the temperature in step (i) is 0-40 °C, most preferably 0-10 °C.
According to still another aspect of the invention, the product in step (i) is dried at 40-80 °C, most preferably 40-60 °C.
According to fifth aspect of the present invention, a process for purification of compound of formula VI i.e. Fexofenadine hydrochloride to get almost impurity free API, was developed which comprises:
(i). reacting an aqueous solution of a,a-Dimethyl-4-[l-hydroxy-4-[4-(hydroxydiphenylmethyl)-l-piperidinyl]butyl] benzene acetic acid hydrochloride (VI) in aliphatic alcohol with caustic & sodium borohydride at elevated temperature,
(ii) isolating Fexofenadine base (V) by ad2-methyl-2-[4-(4-chlorobutanoyI)justing neutral pH followed by filtration & drying to get pure compound (V),
(iii) reacting compound of formula (V) with aq caustic
(iv) converting into Fexofenadine hydrochloride hydrate using aq Hydrochloric acid,
(v) recrystallizing in aliphatic alcohol & aliphatic ester

(vi) filtering the resulting solid and drying to get almost impurity free anhydrous fexofenadine hydrochloride of formula VI.
According to one aspect of the invention, the aliphatic alcohol used in step (i)& (v) is selected from methanol, ethanol, propanol, butanol and/or a mixture thereof
According to another aspect of the invention, the aliphatic ester used in step (v) is selected from ethyl acetate, propyl acetate etc, and/or a mixture thereof
According to yet another aspect of the invention, the temperature in step (v) for crystallization is 0-40 °C, most preferably 0-15 °C.
According to still another aspect of the invention, the product in step (vi) is dried at 40-80 °C, most preferably 40-60 °C.
According to sixth aspect of the present invention, a single analytical method for HPLC analysis of simultaneous detection of keto Fexofenadine, meta keto Fexofenadine and meta Fexofenadine which is given below:
Preparation of Buffer
Dissolve about 3.85 gm of Ammonium acetate in one liter of water. Filter through 0.45 |im or finer porosity membrane filter.
Preparation of Mobile Phase
Prepare a solution of Buffer: methanol in the ratio of 480: 520 (v/v). Use mobile phase as a diluent.

Chromatographic Parameters
Use a suitable High Performance Liquid Chromatograph (HPLC) with following parameters.
Column : Waters Novapak phenyl (150mmx3.9mm) 4µ
Flow rate : 1.0ml/min
Detector : UV at λ=220nm
Injection volume : 10µl
Run time : 40min
Preparation of standard reference Solution.
Accurately weigh and transfer about 20 mg each of Impurity B and fexofenadine to a 100ml of volumetric flask. Dissolve in methanol by sonication if necessary and dilute to volume with methanol. Further take 1ml of this solution in 100ml volumetric flask and make up with the diluent.
Preparation of Sample Solution.
Accurately weigh and transfer about 100 mg of sample to a 50ml of volumetric flask. Dissolve in 5ml of methanol by sonication if necessary and dilute to volume with diluent.
Procedure
Inject 10 ul each of blank (diluent) and sample solutions and record the chromatograms.
Examine the blank run chromatograms for any extraneous peaks and disregard any
Corresponding peaks observed in the chromatogram of the sample solution.

Name of Compound
RT
Fexofenedine HC1 (VI) 7.5 min
Impurity A (keto Fexofenadine; VII) 11.7 min
Impurity B (meta Fexofenadine; VIII) 9.4 min
Impurity C (meta keto Fexofenadine; IX) 14.5 min
Calculation
AT DS
% Impurity = x x PF
AS DT
Where,
AT : Peak area counts of Impurity n the chromatograms of the
Sample solution.
AS : Average peak area counts of standard in the chromatograms of the
Standard solution as obtained under system suitability.
DT : Dilution factor of the sample solution
DS : Dilution factor of the standard solution
PF : Purity Factor

The Fexofenadine hydrochloride & Fexofenadine base used were prepared as per conventional methods.
The above mentioned invention is supported by the following non limiting examples.
Novel amine salts of 2-methyl-2-[4-(4-chlorobutanoyl) phenyl propanoic acid having following structure.
(Formula Removed)
EXAMPLES:
Example 1:
Preparation of 2-Methyl-2-[4-(4-chlorobutanoyl) phenyl propanoic acid dicyclohexylamine salt (III)
To 1.0 kg of crude 2-methyl-2-[4-(4-chlorobutanoyl) phenyl methyl propanoate (II) in 6.0 liter of methanol, aq. caustic solution (0.30 kg) is added and reaction mass is heated to refluxing. The completion of the reaction was monitored by TLC. After 15-16 hrs, the methanol was recovered under vacuum to get a viscous semi solid mass. The product was

extracted in Toluene at (1.0 liter) at acidic pH of about 1.0-2.0 adjusted by HCl (0.65 Liter) followed by washing of organic layer with water. To the toluene layer, dicyclohexylamine was added and 2-methyl-2-[4-(4-chlorobutanoyl) phenyl propanoic acid dicyclohexylamine salt (III) was isolated by adding hexane at 0-10 °C. The crude compound of formula III is further purified in Toluene-hexane to get pure compound of formula III.
Yield = 1.0kg (HPLC purity = 99.24 %; Meta isomer not detected)
Example 2:
Preparation of pure 2-methyl-2-[4-(4-chlorobutanoyl) phenyl methyl propanoate (II)
To a solution/suspension of 1.0 kg of 2-methyl-2-[4-(4-chlorobutanoyl) phenyl propanoic acid dicyclohexylamine salt (III) in methylene chloride (5.0 liter), water (4.0 liter) was added. The reaction mass was stirred & its pH was adjusted to 1.0-2.0 by aq. hydrochloric acid (0.25 liter). The organic layer was separated followed by its washing with water. Complete recovery of solvent is done. The residue is reacted with methanolic hydrogen chloride gas at 20-40 °C followed by complete recovery of methanol and extraction of resulting product with methylene chloride (5.0 liter). Complete recovery of solvent was done to get highly pure 2-methyl-2-[4-(4-chlorobutanoyl) phenyl methyl propanoate (II).
Yield 0.50kg (HPLC purity >98%; Meta isomer Not detected).
Example 3:
Preparation of α,α-Dimethyl-4-[l-oxo-4-[4-(hydroxydiphenyImethyl)-l-
piperidinyl]butyl] phenyl methyl acetate (IV)

A solution/suspension of pure 2-methyl-2-[4-(4-chlorobutanoyl) phenyl methyl propanoate (l00g) in acetone (100ml) & water (300ml) was reacted with a, a-diphenyl-4-piperidinomethanol (85g) in presence of potassium bicarbonate (54g) , potassium iodide (0.55g) at 60-70 °C. The completion of reaction is monitored by HPLC. After 24 hr, solvent & water were recovered under vacuum to give viscous solid mass. Then ethanol (100ml) is added to it and resulting solid is filtered and dried at 40-50 °C to get compound of formula IV.
Yield 135 g (HPLC purity >95 %)
Example 4:
Purification of α,α-Dimethyl-4-[l-oxo-4-[4-(hydroxydiphenylmethyl)-l-
piperidinyl] butyl] phenyl methyl acetate (IV)
a,a-Dimethyl-4- [ 1 -oxo-4- [4-(hydroxydiphenylmethyl)-1 -piperidinyljbutyl] Phenyl methyl acetate (l00g) was dissolved in 1.0 Liter of ethanol at 40-50 °C followed by carbon treatment. The resulting filtered ethanol layer was cooled to 0-5 °C. The material, thus crystallized, was filtered and dried at 40-50 °C to get pure compound IV.
Yield = 90g (HPLC purity = 99.42 %; Meta isomer < 0.20%).
Example 5:
Purification of α,α-Dimethyl-4-[l-oxo-4-[4-(hydroxydiphenylmethyl)-l-
piperidinyl] butyl] phenyl methyl acetate (IV)
a,a-Dimethyl-4-[l-oxo-4-[4-(hydroxydiphenylmethyl)-l-piperidinyl]butyl]Phenyl methyl acetate (l00g) was dissolved in 0.50 Liter of acetone at 40-50 °C followed by carbon

treatment. The resulting filtered ethanol layer was cooled to 0-5 °C. The material, thus crystallized, was filtered and dried at 40-50 °C to get pure compound IV.
Yield = 85g (HPLC purity = 99.11%; Meta isomer not detected).
Example 6:
Purification of α,α-Dimethyl-4-[l-hydroxy-4-[4-(hydroxydiphenylmethyl)-l-
piperidinyl] butyl] benzene acetic acid (V).
To a suspension of a,a-Dimethyl-4-[l-hydroxy-4-[4-(hydroxydiphenylmethyl)-l-
piperidinyl]butyl] benzene acetic acid (100g) in Methanol (300ml), N,N-dimethylformamide
(100ml) is added to get clear solution. The resulting solution was cooled to 0-5 °C and the
solid, thus crystallize, was filtered and dried at 50-60 °C to get pure fexofenadine base. i.e.
a,a-Dimethyl-4-[l-hydroxy-4-[4-(hydroxydiphenylmethyl)-l-piperidinyl]butyl] benzene
acetic acid (V).
Yield = 90 g. (HPLC purity =99.97%; Keto isomer = 0.007 %; Meta isomer not detected).
Example 7:
Purification of α,α-Dimethyl-4-[l-hydroxy-4-[4-(hydroxydiphenylmethyl)-l-
piperidinyl] butyl] benzene acetic acid hydrochloride (VI).
To a solution of a,a-Dimethyl-4-[l-hydroxy-4-[4-(hydroxydiphenylmethyl)-l-piperidinyl]butyl] benzene acetic acid hydrochloride (100g) in Methanol (500ml), aq. caustic solution (30%) was added and reaction mass was heated up to 50-55 °C, followed by the addition of sodium borohydride (2g) & the reaction mass was refluxed for 1.0 hour at 65-70

°C. The reaction mass was cooled to 50-55 °C again and its pH was adjusted to 6.4-6.6 by dilute hydrochloric acid. The resulting mass was cooled to 0-5 °C and stirred for 2-3 hours followed by filtration to get wet cake. To this wet cake, methanol (300ml) & N,N-dimethylformamide (100ml) was added and mixture was refluxed at 70-80 °C for 1 hr. The reaction mass was then cooled to 0-5 °C to re-crystallize the material. Material formed was filtered & finally dried to give pure a,a-Dimethyl-4-[l-hydroxy-4-[4-(hydroxydiphenylmethyl)-l-piperidinyl]butyl] benzene acetic acid (V).
The suspension of pure compound of formula V, thus obtained, in water (160ml) was reacted with aq caustic solution to get clear solution which was converted into fexofenadine hydrochloride hydrate by adding aq HCI. The solid, thus obtained, was filtered & dried to get fexofenadine hydrochloride hydrate. It is recrystallized in isopropyl alcohol (300ml) & ethyl acetate (700ml) followed by filtration and drying at 60-70 °C to get anhydrous fexofenadine hydrochloride of formula VI.
Yield = 90g (HPLC purity 99.95%; Keto Isomer = 0.02 %; Meta isomer not detected; Assay = 99.95 %)
Advantages
1. Novel Fexofenadine intermediate amine salts of formula III.
2. Present invention is capable of producing almost impurity free Fexofenadine hydrochloride

3. Novel purification processes for Fexofenadine Intermediates of formula II & IV to get high purity and very less meta isomer (almost not detected) can be produced by following the processes reported in present invention.
4. The processes reported in present invention are equally effective at commercial scale.
5. By using HPLC analytical method reported in present invention, keto Fexofenadine, meta keto Fexofenadine & meta Fexofenadine impurities can be separated using single method which otherwise are separately analysed using two different analytical methods as reported in pharmacopoeia. Rather meta keto Fexofenadine appears at the same retention time as keto Fexofenadine by pharmacopeial analytical methods & can not be separated whereas these are easily separated using analytical method reported in present invention.

We Claim:
1. Novel amine salts of 2-methyl-2-[4-(4-chlorobutanoyl) phenyl propanoic acid
having following structure.
(Formula Removed)
2. A process for the preparation of the intermediate of claim 1, which comprises
a) Hydrolysis of 2-methyl-2-[4-(4-chlorobutanoyl) phenyl propanoate to
its respective acid by its treatment with caustic solution in methanol.
b) Treatment of 2-methyI-2-[4-(4-chlorobutanoyl) phenyl propanoic acid
is with a amine, in an organic solvent.
3. A process of claim 2, wherein the solvent used in step (a) is C1-C6 aliphatic alcohol
such as methanol, ethanol, isopropyl alcohol, butanol, tert-butanol or a mixture
thereof
4. A process of claim 2, wherein the amine used in step (b) is an organic aliphatic or aromatic amine selected from dicyclohexyl amine, cyclohexyl amine, tert-butyl amine, mono methyl amine, phenylhydrazine, NH3, benzylamine, tris-(hydroxymethyl)aminomethane, a,a -diphenyl-4-piperidinemethanol.

5. A process of claim 2, where the solvent used in step(b) is selected from aliphatic or aromatic halogenated/non halogenated hydrocarbon such as methylene dichloride, chloroform, toluene, xylene, aliphatic esters like ethyl acetate, isopropyl acetate or mixtures thereof.
6. A process for the preparation of highly pure α,α-Dimethyl-4-[l-oxo-4-[4-(hydroxydiphenylmethyI)-l-piperidinyl]butyI]Phenyl methyl acetate, which comprises
a) Treatment of amine salt compound of formula I in claim 1 with an acid, to its
free acid analogue.
b) Reacting the resulting 2-methyl-2-[4-(4-chIorobutanoyl) phenyl propanoic
acid with methanolic hydrogen chloride gas to get pure 2-methyl-2-[4-(4-chlorobutanoyl) phenyl propanoate.
c) Converting the pure 2-methyl-2-[4-(4-chlorobutanoyl) phenyl propanoate to
α,α-Dimethyl-4- [ 1 -oxo-4- [4-(hy droxy diphenylmethyl)-1-piperidinyl] butyl] Phenyl methyl acetate by reaction in an aliphatic ketone, preferably acetone by reaction with azacyclonol.
d) Dissolving crude α,α-Dimethyl-4-[l-oxo-4-[4-(hydroxydiphenylmethyl)-l-
piperidinyl] butyl] Phenyl methyl acetate in an C1-C6 aliphatic alcohol such as methanol, ethanol, isopropyl alcohol, butanol, tert-butanol, aliphatic ketone such as acetone or a mixture thereof preferably ethanol.

e) Crystallizing the material at 0-5 °C to give pure a,a-Dimethyl-4-[l-oxo-4-(4-(hydroxydiphenylmethyl)-l-piperidinyl]butyl]Phenyl methyl acetate after filtration and drying.
7. A Process for the purification of α,α-Dimethyl-4-[l-hydroxy-4-[4-(hydroxydiphenyImethyl)-l-piperidinyl]butyl] benzene acetic acid (Fexofenadine base ) which comprises
a) Dissolution of crude α,α-Dimethyl-4-[l-hydroxy-4-[4-(hydroxydiphenyl niethyl)-l-piperidinyl]butyl] benzene acetic acid, in an aliphatic alcohol, preferably methanol, ethanol, t-butyl alcohol, propyl alcohol, and most preferably in methanol
b) addition of caustic solution
c) Addition of sodium borohydride at elevated temperature at 50-55 °C.
d) Refluxing for 1 -2 hours
e) Cooling at pH 6.4-6.6
f) recrystallization of product at 0-5 °C to get crude product.
g) Purification of Fexofenadine base of step (f) above in a mixture of Methanol & N,N-Dimethylformamide (3:1) to get almost impurity free Fexofenadine.
The material is pure α,α-Diniethyl-4-[l-hydroxy-4-[4-(hydroxydiphenylmethyl)-l-
piperidinyl]butyl] benzene acetic acid in step (g) free from not only Meta isomer but also

from keto impurity. This Fexofenadine base obtained can be converted to highly pure Fexofenadine hydrochloride.
8. A Process for the purification of α,α-Dimethyl-4-[l-hydroxy-4-[4-
(hydroxydiphenylmethyI)-l-piperidinyl]butyl] benzene acetic acid hydrochloride,
which comprises
a) Dissolution of crude α,α-Diniethyl-4-[l-hydroxy-4-[4-(hydroxydiphenyImethyi)-l-piperidinyl]butyl] benzene acetic acid hydrochloride, in an aliphatic alcohol, preferably methanol, ethanol, t-butyl alcohol, propyl alcohol, and most preferably in methanol
b) addition of caustic solution
c) Addition of sodium borohydride at about 50-55 °C.
d) Refluxing for 1 -2 hours
e) Cooling at pH 6.4-6.6, followed by its stirring at this temperature.
f) Recrystallizing the product to get Fexofenadine hydrochloride (API) of high purity.
9. Improved processes for highly pure fexofenadine hydrochloride and its intermediates as described in the specification and illustrated in the accompanying drawings.