FORM 2
THE PATENT ACT, 1970
(39 of 1970)
&
The Patents Rules, 2003
COMPLETE SPECIFICATION
(See section 10 and rule 13)
Title of the invention:
"AN IMPROVED PROCESS FOR THE PREPARATION OF FLUPHENAZINE"
Applicant:
Enaltec Labs Pvt. Ltd. an Indian Company, having its Registered Office at 17th Floor, Kesar
Solitaire, Plot No.5 Sector-19, Sanpada, Navi Mumbai Maharashtra, India. Pin Code: 400705
Preamble:
1. The following specification particularly describes the invention and the manner in which it is to be performed.

FIELD OF THE INVENTION:
The present invention relates to an improved process for the preparation of fluphenazine or its salts or esters.
BACKGROUND OF THE INVENTION:
Fluphenazine is chemically defined as 4-[3-[2-(Trifluoromethyl) phenothiazin-10-yl] propyl]-1-piperazineethanol. It is known from U.S. Patent Nos. 3,058,979 and 3,394,131 and is represented by compound of structural formula I.

Fluphenazine is a typical antipsychotic drug available in market as Fluphenazine Hydrochloride and Fluphenazine Decanoate indicated for:
• Management of manifestations of psychotic disorders
• Management of patients requiring prolonged parenteral neuroleptic therapy (e.g., chronic schizophrenics).
U.S. Patent No. 3,058,979 describes a process for the preparation of fluphenazine compound of structural formula I and its hydrochloride salt of structural formula II as shown below in scheme no. 1.


U.S. Patent No. 3,394,131 describes a process for the preparation of fluphenazine decanoate compound of structural formula III as shown below in scheme no. 2.


U.S. Patent No. 3,054,791 describes a process for the preparation of fluphenazine derivative as shown below in scheme no. 3.

U.S. Patent No. 3,966,930 describes a process for the preparation of fluphenazine derivative as shown below in scheme no. 4.


The prior art processes for the preparation of fluphenazine compound of structural formula I are not commercially viable due to formation of impurity represented by compound of structural formula XXXI along with fluphenazine.

The purification of which resulted into low yield of pure fluphenazine compound of structural formula I and therefore there is a need in the art to develop an improved process for the preparation of fluphenazine compound of structural formula I, which produces high yield of fluphenazine compound of structural formula I.
SUMMARY OF THE INVENTION:
A first aspect of the present invention is to provide a commercial viable process for the preparation of fluphenazine, which obviates the prior art problems
A second aspect of the present invention is to provide an improved process for the preparation of fluphenazine compound of structural formula I.
Another aspect of the present invention is to provide an improved process for the preparation of fluphenazine compound of structural formula I comprising the steps of:
a. protecting compound of structural formula XX with protecting agent to get compound of structural formula XXI,


b. condensing compound of structural formula XXI with compound of structural formula IV to get compound of structural formula XXII and

c. deprotecting compound of structural formula XXII to get fluphenazine compound of structural formula I.

wherein, P is protecting group such as benzyl, tetrahydropyranyl, trityl, trimethylsilyl, tert-butyldimethylsilyl, acetyl or any other alcohol protecting group.
Another aspect of the present invention is to provide an improved process for the preparation of fluphenazine or its salts or esters comprising the steps of:
a. protecting compound of structural formula XX with protecting agent to get compound of structural formula XXI,

b. condensing compound of structural formula XXI with compound of structural formula IV to get compound of structural formula XXII,


c. deprotecting compound of structural formula XXII to get fluphenazine compound of structural formula I and

wherein, P is protecting group such as benzyl, tetrahydropyranyl, trityl, trimethylsilyl, tert-butyldimethylsilyl, acetyl or any other alcohol protecting group. d. converting fluphenazine compound of structural formula I in to its salts or esters.
Another aspect of the present invention is to provide an improved process for the preparation of fluphenazine compound of structural formula I comprising the steps of:
a. protecting compound of structural formula XX with tert-butyldimethylsilyl chloride to get compound of structural formula XXIII,


b. condensing compound of structural formula XXIII with compound of structural formula IV to get compound of structural formula XXIV and

c. deprotecting compound of structural formula XXIV to get fluphenazine compound of structural formula I.

Another aspect of the present invention is to provide an improved process for the preparation of fluphenazine compound of structural formula I comprising the steps of:
a. protecting compound of structural formula XX with trimethylsilyl chloride to get compound of structural formula XXV,

b. condensing compound of structural formula XXV with compound of structural formula IV to get compound of structural formula XXVI and


c. deprotecting compound of structural formula XXVI to get fluphenazine compound of structural formula I.

Another aspect of the present invention is to provide an improved process for the preparation of fluphenazine compound of structural formula I comprising the steps of:
a. protecting compound of structural formula XX with trityl chloride to get compound of structural formula XXVII,

b. condensing compound of structural formula XXVII with compound of structural formula IV to get compound of structural formula XXVIII and


c. deprotecting compound of structural formula XXVIII to get fluphenazine compound of structural formula I.

Another aspect of the present invention is to provide an improved process for the preparation of fluphenazine compound of structural formula I comprising the steps of:
a. protecting compound of structural formula XX with dihydropyran to get compound of structural formula XXIX,

b. condensing compound of structural formula XXIX with compound of structural formula IV to get compound of structural formula XXX and


c. deprotecting compound of structural formula XXX to get fluphenazine compound of structural formula I.

Another aspect of the present invention is to provide an improved process for the preparation of fluphenazine compound of structural formula I comprising the steps of:
a. reacting compound of structural formula XXI with compound of structural formula IV to get compound of structural formula XXII,

b. deprotecting compound of structural formula XXII to get fluphenazine compound of structural formula I.


wherein, P is protecting group such as benzyl, tetrahydropyranyl, trityl, trimethylsilyl, tert-butyldimethylsilyl, acetyl or any other alcohol protecting group.
Another aspect of the present invention is to provide an improved process for the preparation of fluphenazine compound of structural formula I comprising the steps of:
a. protecting compound of structural formula XX with acetylating agent to get compound of structural formula XXXII,

b. condensing compound of structural formula XXXII with compound of structural formula IV to get compound of structural formula IX and

c. deprotecting compound of structural formula IX to get fluphenazine compound of structural formula I.


Another aspect of the present invention is to provide an improved process for the preparation of fluphenazine hydrochloride compound of structural formula II comprises, obtaining fluphenazine by the process of the present invention and converting it in to fluphenazine hydrochloride compound of structural formula II.
Another aspect of the present invention is to provide an improved process for the preparation of fluphenazine decanoate compound of structural formula III comprises, obtaining fluphenazine by the process of the present invention and converting it in to fluphenazine decanoate compound of structural formula III.
DETAIL DESCRIPTION OF THE INVENTION:
The present invention provides an improved process for the preparation of fluphenazine compound of structural formula I or its salts or esters.
The compound of structural formula XX used herein may be prepared by the processes known in the art such as those described in Zhurnal Obshchei Khimii, 32, p. 2244-2248, (1962), Zhongguo Yiyao Gongye Zazhi, 22 (12), p 535-6, Journal, (1991) which are incorporated herein by reference only.
The compound of structural formula XX used herein may be in the form of base or its dihydrochloride salt.

The dihydrochloride salt of compound of structural formula XX may be prepared by reacting 2-(piperazine-1-yl) ethanol with l-bromo-3-chloropropane in presence potassium carbonate in acetone solvent at a temperature in the range of 25°C to 40°C for a period of 1 hour to 14 hours to get compound of structural formula XX and then treating compound of structural formula XX with isopropanolic hydrochloride solution at temperature in the range of -5°C to 10°C to get dihydrochloride salt of compound of structural formula XX.
The dihydrochloride salt of compound of structural formula XX may be isolated by the steps of filtration, centrifugation, washing, drying or the combinations thereof.
The compound of structural formula XXI may be prepared by reacting compound of structural formula XX or its dihydrochloride salt with protecting agent in presence of organic base in non-polar organic solvent.
The examples of protecting agent may include but not limited to tert-butyldimethylsilyl chloride, trimethylsilyl chloride, trityl chloride, dihydropyran or acetylating agent such as acetic anhydride or acetyl chloride.
The examples of organic base may include but not limited to triethylamine, diisopropylamines, imidazole, pyridine, pyridazine, pyrimidine, lithium diisopropylamide, potassium bis(trimethylsilylamide), potassium tert-butoxide, dimethyl amino pyridine, 1,8-Diazabicyclo[5.4.0]undec-7-ene (DBU) or l,5-Diazabicyclo[4.3.0]non-5-ene(DBN) etc.
The examples of non-polar organic solvent may include but not limited to chloroform, dichloromethane, dichloroethane, diethyl ether, methyl tertiary-butyl ether, 1,4-dioxane, toluene, pentane, cyclopentane, hexane, cyclohexane or mixture(s) thereof.
The reaction of compound of structural formula XX or its dihydrochloride salt with protecting agent may be carried out at a temperature in the range of 20°C to 50°C for a period of 30 minutes to 4 hours to get compound of structural formula XXL

The compound of structural formula XXI may be isolated by the steps of filtering reaction mixture, adding water to the filtrate, separating organic layer, drying organic layer over sodium sulphate and concentrating resulting organic layer to get compound of structural formula XXI as oily mass.
The compound of structural formula XXII may be prepared by condensing the compound of structural formula XXI with compound of structural formula IV in presence of above mentioned organic base in polar aprotic solvent.
The examples of polar aprotic solvent may include but not limited to acetone, acetonitrile, dimethylformamide, dimethyl sulfoxide, ethyl acetate, nitromethane, propylene carbonate, tetrahydrofuran or mixture(s) thereof.
The reaction of compound of structural formula XXI with compound of structural formula IV may be carried out at a temperature in the range of 20°C to 35°C for a period of 1 hour to 14 hours to get compound of structural formula XXII.
The compound of structural formula XXII may be isolated by quenching the reaction mixture with water and extracting it with toluene. The organic layer containing compound of structural formula XXII may be washed with water followed by treating it with aqueous sodium dithionite solution (1%) and again washed with water. The resulting organic layer was dried over sodium sulphate and then concentrated under reduced pressure to get compound of structural formula XXII as brown liquid.
The fluphenazine compound of structural formula I may be prepared by deprotecting compound of structural formula XXII in presence of inorganic acid in polar protic solvent or above mentioned non-polar organic solvents or mixture thereof.
The inorganic acid used herein may be in the form of concentrated or aqueous solution.

The examples of inorganic acid may include but not limited to hydrochloric acid, hydrobromic acid, nitric acid, sulfuric acid, phosphoric acid and the like.
The examples of polar protic solvent may include but not limited to methanol, ethanol, n-butanol, isopropanol, n-propanol or mixture(s) thereof.
The deprotection of compound of structural formula XXII may be carried out at a temperature in the range of 25°C to 50°C for a period of 2 hours to 24 hours.
The fluphenazine compound of structural formula I may be isolated by adding water to the reaction mixture, extracting it with toluene to get organic layer. The resulting organic layer was treated with water and organic layer was separated. The remaining aqueous layer was basified with potassium carbonate up to pH 7-8 and then extracted with toluene. The all organic layer was combined and treated with activated charcoal followed by filtered through hyflobed and hyflobed washed with toluene to get filtrate. The resulting filtrate was treated with aqueous sodium dithionite solution (2%), washed with water, dried over sodium sulphate and concentrated under reduced pressure to get fluphenazine compound of structural formula I as yellow oil.
Optionally, the fluphenazine compound of structural formula I may be further purified by preparing organic acid addition salt of fluphenazine compound of structural formula I and then converting organic acid addition salt of fluphenazine compound of structural formula I in to pure fluphenazine compound of structural formula I.
The organic acid addition salt of fluphenazine compound of structural formula I may be prepared by reacting fluphenazine compound of structural formula I with organic acid in above mentioned polar aprotic solvent at a temperature in the range of 20°C to 55°C for a period of 20 minutes to 2 hours.
The examples of organic acid may include but not limited to maleic acid, fumaric acid, oxalic acid, tartaric acid, citric acid or succinic acid. Preferably organic acid may include maleic acid.

The organic acid addition salt of fluphenazine compound of structural formula I may be isolated by the steps of filtration, centrifugation, washing, drying or the combinations thereof.
The organic acid addition salt of fluphenazine compound of structural formula I may be converted in to pure fluphenazine compound of structural formula I by treating organic acid addition salt of fluphenazine compound of structural formula I with inorganic base in above mentioned non-polar organic solvent at a temperature in the range of 10°C to 35°C for a period of 15 minutes to 1 hour to get pure fluphenazine compound of structural formula I.
The examples of inorganic base may include but not limited to hydroxides alkali metal or alkaline earth metal such as sodium hydroxide, potassium hydroxide, lithium hydroxide, calcium hydroxide, barium hydroxide; bicarbonates of alkali metal such as sodium bicarbonate, potassium bicarbonate etc.
The pure fluphenazine compound of structural formula I may be isolated by separating organic layer from the reaction mixture, washed with water, dried over sodium sulphate and concentrated under reduced pressure to get pure fluphenazine compound of structural formula I as dark yellow viscous oil.
The pure fluphenazine compound of structural formula I may be converted in to fluphenazine hydrochloride compound of structural formula II by treating pure fluphenazine compound of structural formula I with alcoholic hydrochloride solution in above mentioned polar protic solvent at a temperature in the range of 0°C to 30°C for a period of 30 minutes to 6 hours to get fluphenazine hydrochloride compound of structural formula II.
The examples of alcoholic hydrochloride solution may include methanolic hydrochloric acid, ethanolic hydrochloric acid or isopropanolic hydrochloric acid.
The alcoholic hydrochloride solution may contain hydrochloric acid in the range of 5% weight / weight to 30% weight / weight.

The fluphenazine hydrochloride compound of structural formula II may be isolated by the steps of filtration, centrifugation, washing, drying or the combinations thereof.
The pure fluphenazine compound of structural formula I may be converted in to fluphenazine decanoate compound of structural formula III by reacting pure fluphenazine compound of structural formula I with decanoyl chloride in presence of above mentioned organic base in above mentioned non-polar organic solvent.
The reaction of pure fluphenazine compound of structural formula I with decanoyl chloride may be carried out at a temperature in the range of 5°C to 40°C for a period of 10 minutes to 2 hours.
The fluphenazine decanoate compound of structural formula III may be isolated by quenching the reaction mixture with aqueous solution of sodium bicarbonate (10%) and then extracted with above mentioned non-polar organic solvent. The resulting organic layer was dried over sodium sulphate and concentrated under reduced pressure to get fluphenazine decanoate compound of structural formula III as yellow oil.
Optionally, the fluphenazine decanoate compound of structural formula III may be further purified by preparing organic acid addition salt of fluphenazine decanoate compound of structural formula III and then converting organic acid addition salt of fluphenazine decanoate compound of structural formula III in to pure fluphenazine decanoate compound of structural formula III.
The organic acid addition salt of fluphenazine decanoate compound of structural formula III may be prepared by reacting fluphenazine decanoate compound of structural formula III with organic acid in above mentioned polar aprotic solvent at a temperature in the range of 20°C to 55°C for a period of 20 minutes to 4 hours.
The examples of organic acid may include but not limited to maleic acid, fumaric acid, oxalic acid, tartaric acid, citric acid or succinic acid. Preferably organic acid may include maleic acid.

The organic acid addition salt of fluphenazine decanoate compound of structural formula III may be isolated by the steps of filtration, centrifugation, washing, drying or ,the combinations thereof.
The isolated organic acid addition salt of fluphenazine decanoate compound of structural formula III may be further purified by treating it with activated charcoal in above mentioned polar protic solvent at a temperature in the range of 20°C to 70°C for a period of 30 minutes to 3 hours.
The pure organic acid addition salt of fluphenazine decanoate compound of structural formula III may be isolated by the steps of filtration, centrifugation, washing, drying or the combinations
thereof.
The pure organic acid addition salt of fluphenazine decanoate compound of structural formula III may be converted in to pure fluphenazine decanoate compound of structural formula III by treating pure organic acid addition salt of fluphenazine decanoate compound of structural formula III with above mentioned inorganic base in above mentioned non-polar organic solvent at a temperature in the range of 10°C to 45°C for a period of 15 minutes to 2 hours to get pure fluphenazine decanoate compound of structural formula III.
The pure fluphenazine decanoate compound of structural formula III may be isolated by separating organic layer from the reaction mixture, washed with water, dried over sodium sulphate and concentrated under reduced pressure to get pure fluphenazine decanoate compound of structural formula III as viscous oil.
The pure fluphenazine compound of structural formula I contain less than 0.15% of impurity represented by compound of structural formula XXXI.
The fluphenazine hydrochloride compound of structural formula II contain less than 0.15% of impurity represented by compound of structural formula XXXI.
The pure fluphenazine decanoate compound of structural formula III contain less than 0.15% of impurity represented by compound of structural formula XXXI.

EXAMPLES:
In the following examples, the preferred embodiments of the present invention are described only by way of illustrating the process of the invention. However, these are not intended to limit the scope of the present invention in any way.
Example 1: Preparation of dihydrochloride salt of 2-(4-(3-chIoropropyl) piperazin-l-yl) ethanol compound of structural formula XX.
A solution of 2-(piperazine-l-yl) ethanol (200 gm) in acetone (800 ml) was added potassium carbonate (531 gm) and stirred for 1 hour at 20-25°C. The resulting reaction mixture was added a solution of 1-bromo-3-chloropropane (314 gm) in acetone (200 ml) and stirred for 12 hours at 25-30°C. The resulting reaction mixture was filtered and washed with acetone (300 ml) to get filtrate. The resulting filtrate was cooled to 0-5°C and then isopropanolic hydrochloride solution (16%, 740 ml) was added to the filtrate up to pH 1 and then resulting reaction mixture was stirred for 2 hours at 0-5°C to get solid. The resulting solids were filtered, washed with acetone (300 ml) and dried at 55-60°C for 5 hours under reduce pressure to get title compound. Yield: 360 gm.
Example 2: Preparation of fluphenazine compound of structural formula I.
Step-1: Preparation of l-(2-(tert-butyldimethylsilyloxy) ethyl)-4-(3-ch!oropropyl)
piperazine compound of structural formula (XXIII).
A solution of dihydrochloride salt of 2-(4-(3-chloropropyl) piperazin-l-yl) ethanol compound of structural formula XX (195 gm) in dichloromethane (1800 ml) was added imidazole (214 gm) and stirred for 1 hour at 25-30°C. The resulting reaction mixture was added solution of tert-butyldimethylsilyl chloride (160 gm) in dichloromethane (400 ml) and stirred for 2 hours at 40-45°C. The resulting reaction mixture was cooled to 25-30°C, filtered and washed with dichloromethane (195 ml) to get filtrate. The resulting filtrate was added water (3x1000ml) and stirred for 20-30 minutes. Then organic layer was separated, dried over sodium sulphate and concentrated under reduce pressure to get title compound as oily mass. Yield: 225 gm.

Step-2: Preparation of 10-(3-(4-(2-(tert-butyldimethylsilyloxy) ethyl) Piperazine-1-yl) propyl) -2-(trifluoromethyl)-10H-phenothiazine compound of structural formula XXIV.
A solution of 2-(trifluoromethyl)-10H-phenothiazine compound of formula IV (80 gm) in dimethyl sulfoxide (620 ml) was added potassium tert-butoxide (33.5 gm) and stirred for 1 hour at 25-30°C. The resulting reaction mixture was added l-(2-(tert-butyldimethylsilyloxy) ethyl)-4-(3-chloropropyl) piperazine compound of structural formula (XXIII) (192.2 gm) and stirred for 12 hours at 20-25°C. The resulting reaction mixture quenched with water (800 ml) and extracted with toluene (2x400 ml) to get organic layer. The resulting organic layer was washed with water (800 ml) and treated with aqueous sodium dithionite solution (1%, 500 ml) and again washed with water (2x800 ml). Then the resulting organic layer dried over sodium sulphate and concentrated under reduced pressure to get title compound as brown liquid. Yield: 250 gm.
Step-3: Preparation of fluphenazine compound of structural formula I.
A solution of 10-(3-(4-(2-(tert-butyldimethylsilyloxy) ethyl) Piperazine-1-yl) propyl) -2-(trifluoromethyl)-lOH-phenothiazine compound of structural formula XXIV (250 gm) in mixture of methanol (750 ml) and dichloromethane (250 ml) was added aqueous hydrochloric acid solution (10%, 1000 ml) at 25-30°C and resulting reaction mixture was heated to 40-45°C for 20 minutes. Then the reaction mixture was stirred for 20 hours at 25-30°C followed by water (500 ml) was added to the reaction mixture and extracted with toluene (2x300 ml) to get organic layer. The resulting organic layer was added water (3x1000 ml), stirred for 30 minutes and organic layer was separated. The remaining aqueous layer was basified with potassium carbonate (60 gm) up to pH 7-8 and extracted with toluene (3x500 ml). The all organic layer was combined and treated with activated charcoal (50 gm) for 1 hour at 25-30°C and then resulting organic layer was filtered through hyflobed and hyflobed washed with toluene (250 ml) to get filtrate. The resulting filtrate was treated with aqueous sodium dithionite solution (2%, 3x250 ml) for 30 minutes and organic layer was separated. The resulting organic layer was washed with water (3x250 ml), dried over sodium sulphate and concentrated under reduced pressure to get title compound as yellow oil. Yield: 70 gm.

Example 3: Purification of fluphenazine compound of structural formula I.
Step-1: Preparation of dimaleate salt of fluphenazine compound of structural formula I.
A solution of fluphenazine compound of structural formula I (60 gm) in acetone (500 ml) was added saturated solution of maleic acid (31.83 gm in 250 ml acetone) at 25-30°C and then the resulting reaction mixture was heated to 40-50°C and stirred for 30 minutes. Then the reaction mixture was gradually cooled to 25-30°C and stirred for 1 hour to get solid. The resulting solids were filtered, washed with acetone (200 ml) and dried at 40-45 °C under reduce pressure. The resulting solids were recrystallized with methanol (500 ml) and dried at 40-45°C under reduce pressure to get title compound. Yield: 72 gm
Step: 2: Preparation of pure fluphenazine compound of structural formula I.
A solution of dimaleate salt of fluphenazine compound of structural formula I (25 gm) in
dichloromethane (150 ml) was added sodium bicarbonate (10 gm) up to pH 8.0 at 10-15°C and
then resulting reaction mixture was stirred for 30 minutes at 25-30°C. Then organic layer was
separated and washed with water (3x250 ml). The resulting organic layer was dried over sodium
sulphate and concentrated under reduced pressure to get title compound as yellow viscous oil.
Yield: 14.5 gm.
Purity: 99.9% (By HPLC)
Impurity compound of structural formula XXXI: less than 0.1%
Example 4: Preparation of fluphenazine hydrochloride compound of structural formula II.
A solution of pure fluphenazine compound of structural formula I (10 gm) in ethanol (100 ml)
was added isopropanolic hydrochloride solution (10%, 15 ml) at 25-30°C and then the resulting
reaction mixture was stirred for 1 hour at 0-5 °C to get solid. The resulting solids were filtered,
washed with ethanol (20 ml) and dried at 40-45 °C for 4 hours under reduced pressure to get title
compound.
Yield: 15 gm
Purity: 99.9% (By HPLC)
Example 5: Preparation of fluphenazine decanoate compound of structural formula III.

A solution of pure fluphenazine compound of structural formula I (13 gm) in dichloromethane (65 ml) was added triethylamine (7.49 gm) at 25-30°C and then the reaction mixture cooled to 10-15°C. The resulting reaction mixture was added decanoyl chloride (11.49 gm) at 10-15 °C and then resulting reaction mixture was stirred for 4 hours at 25-30°C. The reaction mixture was cooled to 10-15°C and quenched with aqueous sodium bicarbonate solution (10%, 100 ml) followed by extracted with dichloromethane (100 ml). The resulting aqueous layer was extracted with dichloromethane (2x100 ml) and then all organic layers were combined, dried over sodium sulphate and concentrated under reduced pressure to get title compound as yellow oil. Yield: 17 gm.
Example 6: Purification of fluphenazine decanoate compound of structural formula III. Step-1: Preparation of dimaleate salt of fluphenazine decanoate compound of structural formula III.
A solution of fluphenazine decanoate compound of structural formula III (38 gm) in acetone (150 ml) was added saturated solution of maleic acid (14.9 gm in 100 ml acetone) at 25-30°C and then the resulting reaction mixture was heated to 40-50°C and stirred for 30 minutes. Then the reaction mixture was gradually cooled to 25-30°C and stirred for 1 hour to get solid. The resulting solids were filtered, washed with acetone (38 ml) and dried at 40-45°C under reduce pressure. The resulting solid was added methanol (630 ml), heated to 60-65°C, stirred for 1 hour and then added activated charcoal (4.2 gm) and stirred for 1 hour. The resulting solution was filtered through hyflobed and resulting filtrate was slowly cooled to 25-30°C and stirred for 2 hours to get solid. The resulting solids were filtered, washed with methanol (100 ml) and dried at 40-45 °C under reduced pressure to get title compound. Yield: 32 gm.
Step: 2: Preparation of pure fluphenazine decanoate compound of structural formula III.
A solution of dimaleate salt of fluphenazine decanoate compound of structural formula III (27 gm) in methyl tertiary-butyl ether (300 ml) was added sodium bicarbonate (17 gm) up to pH 8.0 at 10-15°C and then resulting reaction mixture was stirred for 30 minutes at 25-30°C. Then organic layer was separated and washed with water (3x250 ml). The resulting organic layer was

dried over sodium sulphate and concentrated under reduced pressure to get title compound as
viscous oil.
Yield: 18.0 gm.
Purity: 99.9% (By HPLC)
Impurity compound of structural formula XXXI: less than 0.1%

WE CLAIM:

comprising;
(a) treating fluphenazine compound of structural formula I:

1. A process for the preparation of fluphenazine hydrochloride the compound of structural formula II:
with alcoholic hydrochloride solution in an organic solvent,
(b) isolating fluphenazine hydrochloride the compound of structural formula II,
(c) and optionally purifying the fluphenazine hydrochloride the compound of structural formula II using alcoholic solvent.

2. The process as claimed in the claim 1, wherein alcoholic hydrochloride solution is selected from the group consisting of methanolic hydrochloric acid, ethanolic hydrochloric acid or isopropanolic hydrochloric acid solution.
3. The process as claimed in the claim 1 or 2, wherein organic solvent used in the step (a) is polar protic solvent.

4. The process as claimed in any of the claim 1 to 3, wherein polar protic solvent selected from the group consisting of methanol, ethanol, n- butanol, isopropanol, n-propanol or mixture(s) thereof.
5. The process as claimed in any of the claim 1 to 4, wherein the reaction of the step (a) is carried out for period of 30 minutes to 6 hours.
6. The process as claimed in any of the claim 1 to 5, wherein the reaction of the step (a) is carried out at a temperature in the range of 0°C to 30°C
7. The process as claimed in any of the claim 1 to 6, wherein the step (b) involving isolation of fluphenazine hydrochloride the compound of formula II from the reaction mixture obtained in the step (a) comprises the steps of:
i. cooling the reaction mixture at a temperature in the range of 0-5°C to precipitate
solid, ii. filtering the precipitated solid to obtain fluphenazine hydrochloride the compound of formula II.
8. The process as claimed in any of the claim 1 to 7, wherein alcoholic solvent used in the step (c) is selected from group consisting of methanol, ethanol, n- butanol, isopropanol, n-propanol or mixture(s) thereof.
9. A process for the preparation of fluphenazine hydrochloride the compound of structural formula II as claimed in the claim 1 comprising;
treating fluphenazine compound of structural formula I:

with alcoholic hydrochloride solution selected from the group consisting of methanolic hydrochloric acid, ethanolic hydrochloric acid or isopropanolic hydrochloric acid solution

in solvent selected from the group consisting of methanol, ethanol, n- butanol, isopropanol, n-propanol or any mixture(s) thereof.
10. A process for the preparation of fluphenazine hydrochloride the compound of structural formula II as claimed in the claim 1 comprising steps of:
(a) treating fluphenazine compound of structural formula I:

with alcoholic hydrochloride solution selected from the group consisting of methanolic hydrochloric acid, ethanolic hydrochloric acid or isopropanolic hydrochloric acid solution in solvent selected from the group consisting of methanol, ethanol, n- butanol, isopropanol, n-propanol or mixture(s) thereof.
(b) isolating fluphenazine hydrochloride the compound of structural formula II,
(c) and optionally washing the fluphenazine hydrochloride the compound of structural formula II using solvent selected from methanol, ethanol, n- butanol, isopropanol, n-propanol or mixture(s) thereof.