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 PERPHENAZINE"
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
1. The following specification particularly describes the invention and the manner in which it is to be performed.

AN IMPROVED PROCESS FOR THE PREPARATION OF PERPHENAZINE
FIELD OF THE INVENTION:
The present invention relates to an improved process for the preparation of perphenazine compound of structural formula I.
BACKGROUND OF THE INVENTION:
Perphenazine is chemically defined as 4-[3-(2-chloro-10H-phenothiazin-10-yl) propyl]-l-piperazineethanol. It is known from U.S. Patent No. 2,838,507 and is represented by compound of structural formula I.
Perphenazine is a typical antipsychotic drug indicated for.
• Management of the manifestations of psychotic disorders;
• For the control of severe nausea and vomiting in adults.
U.S. Patent No. 2,838,507 describes a process for the preparation of perphenazine compound of structural formula I as shown below in scheme no. 1.

U.S. Patent No. 2,860,138 describes a process for the preparation of perphenazine compound of structural formula I as shown below in scheme no. 2.

German Patent No. 1174320 describes the processes for the preparation of perphenazine derivative as shown below in scheme nos. 3, 4, and 5.
U.S. Patent No. 3,966,930 describes a process for the preparation of perphenazine derivative as shown below in scheme no. 6.

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

The purification of which resulted into low yield of pure perphenazine compound of structural formula I and therefore there is a need in the art to develop an improved process for the preparation of perphenazine compound of structural formula I, which produces high yield of perphenazine 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 perphenazine, which obviates the prior art problems.
A second aspect of the present invention is to provide an improved process for the preparation of perphenazine compound of structural formula I.
Another aspect of the present invention is to provide an improved process for the preparation of perphenazine compound of structural formula I comprising the steps of:
a. protecting compound of structural formula XVII with protecting agent to get compound of structural formula XVIII,
b. condensing compound of structural formula XVIII with compound of structural formula VI to get compound of structural formula XIX and

c. deprotecting compound of structural formula XIX to get perphenazine compound of structural formula I.
wherein, P is protecting group such as benzyl, tetrahydropyranyl, trityl, trimethylsilyl, tert-butyldimethylsilyl or any other alcohol protecting group.
Another aspect of the present invention is to provide an improved process for the preparation of perphenazine compound of structural formula I comprising the steps of:
a. protecting compound of structural formula XVII with tert-butyldimethylsilyl chloride to get compound of structural formula XX,
b. condensing compound of structural formula XX with compound of structural formula VI to get compound of structural formula XXI and

c. deprotecting compound of structural formula XXI to get perphenazine compound of structural formula I
Another aspect of the present invention is to provide an improved process for the preparation of perphenazine compound of structural formula I comprising the steps of:
a. protecting compound of structural formula XVII with trimethylsilyl chloride to get compound of structural formula XXII,
b. condensing compound of structural formula XXII with compound of structural formula VI to get compound of structural formula XXIII and

c. deprotecting compound of structural formula XXIII to get perphenazine compound of structural formula I.
Another aspect of the present invention is to provide an improved process for the preparation of perphenazine compound of structural formula I comprising the steps of:
a. protecting compound of structural formula XVII with trityl chloride to get compound of structural formula XXIV,
b. condensing compound of structural formula XXIV with compound of structural formula VI to get compound of structural formula XXV and
c. deprotecting compound of structural formula XXV to get perphenazine compound of structural formula I.

Another aspect of the present invention is to provide an improved process for the preparation of perphenazine compound of structural formula I comprising the steps of:
a. protecting compound of structural formula XVII with dihydropyran to get compound of structural formula XXVI,
b. condensing compound of structural formula XXVI with compound of structural formula VI to get compound of structural formula XXVII and
c. deprotecting compound of structural formula XXVII to get perphenazine compound of structural formula I.

Another aspect of the present invention is to provide an improved process for the preparation of perphenazine compound of structural formula I comprising the steps of:
a. reacting compound of structural formula XVIII with compound of structural formula VI to get compound of structural formula XIX and
b. deprotecting compound of structural formula XIX to get perphenazine compound of structural formula I.
wherein, P is protecting group such as benzyl, tetrahydropyranyl, trityl, trimethylsilyl, tert-butyldimethylsilyl or any other alcohol protecting group.

Another aspect of the present invention is to provide an improved process for the preparation of perphenazine compound of structural formula I comprising the steps of:
a. protecting compound of structural formula XVII with acetylating agent to get compound of structural formula XXIX,
b. condensing compound of structural formula XXIX with compound of structural formula VI to get compound of structural formula XXX and
c. deprotecting compound of structural formula XXX to get perphenazine compound of structural formula I.

DETAIL DESCRIPTION OF THE INVENTION:
In one embodiment of the present invention provides an improved process for the preparation of perphenazine.
The compound of structural formula XVII 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 XVII used herein may be in the form of base or its dihydrochloride salt.
The dihydrochloride salt of compound of structural formula XVII 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 XVII and then treating compound of structural formula XVII with isopropanolic hydrochloride solution at temperature in the range of-5°C to 10°C to get dihydrochloride salt of compound of structural formula XVII.
The dihydrochloride salt of compound of structural formula XVII may be isolated by the steps of filtration, centrifugation, washing, drying or the combinations thereof.
In one embodiment of the invention, the compound of structural formula XVIII may be prepared by reacting compound of structural formula XVII 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, 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 XVII 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 XVIII.
The compound of structural formula XVIII 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 XVIII as oily mass.
The compound of structural formula XIX may be prepared by condensing the compound of structural formula XVIII with compound of structural formula VI 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 XVIII with compound of structural formula VI may be carried out at a temperature in the range of 20°C to 40°C for a period of 1 hour to 14 hours to get compound of structural formula XIX.

The compound of structural formula XIX may be isolated by quenching the reaction mixture with water and extracting it with toluene. The organic layer containing compound of structural formula XIX 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 XIX as brown liquid.
The perphenazine compound of structural formula I may be prepared by deprotecting compound of structural formula XIX 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 XIX 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 perphenazine 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 solid. The resulting solids were recrystallized with acetone to get perphenazine compound of structural formula I.

The perphenazine compound of structural formula I may also purified by the process of recrystallization in ethyl acetate or isopropyl alcohol solvent.
The isolated perphenazine compound of structural formula I may be dried at a temperature in the range of 40°C to 60°C for a period of 30 minutes to 4 hours.
In another embodiment of the invention, the compound of structural formula XXIX may be prepared by reacting compound of structural formula XVII or its dihydrochloride salt with acetylating agent in presence of above mentioned organic base in above mentioned non-polar organic solvent.
The examples of acetylating agent may include but not limited to acetic anhydride or acetyl chloride.
The reaction of compound of structural formula XVII or its dihydrochloride salt with acetylating agent may be carried out at a temperature in the range of 15°C to 50°C for a period of 30 minutes to 12 hours to get compound of structural formula XXIX.
The compound of structural formula XXIX may be isolated by quenching the reaction mixture with water and separating organic layer. The remaining aqueous layer extracted with above mentioned non-polar organic solvent. The all organic layers were combined, washed with water, treated with aqueous sodium bicarbonate solution (2%) and again washed with water. The resulting organic layer dried over sodium sulphate and concentrated under reduced pressure to get compound of structural formula XXIX as yellow oil.
The compound of structural formula XXX may be prepared by condensing the compound of structural formula XXIX with compound of structural formula VI in presence of above mentioned organic base in above mentioned polar aprotic solvent.

The reaction of compound of structural formula XXIX with compound of structural formula VI may be carried out at a temperature in the range of 20°C to 60°C for a period of 1 hour to 8 hours to get compound of structural formula XXX.
The compound of structural formula XXX may be isolated by quenching the reaction mixture with ice cold water and extracting it with toluene. The resulting organic layer may be washed with water followed by treated with aqueous hydrochloric acid solution (10%) up to pH 1 and then aqueous layer was separated. The resulting organic layer extracted with aqueous hydrochloric acid solution (10%) and then all aqueous layers were combined and extracted with toluene. The remaining aqueous layer was basified with aqueous potassium carbonate solution up to pH 8-9 and extracted with toluene. The resulting organic layer was washed with water, dried over sodium sulphate and concentrated under reduce pressure to get compound of structural formula XXX as brown oily liquid.
The perphenazine compound of structural formula I may be prepared by deprotecting compound of structural formula XXX in presence of inorganic base in above mentioned polar protic solvent.
The inorganic base used herein may be in the form of aqueous solution.
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 deprotection of compound of structural formula XXX may be carried out at a temperature in the range of 20°C to 70°C for a period of 1 hour to 8 hours.
The perphenazine compound of structural formula I may be isolated by quenching the reaction mixture with ice cold water and extracted with toluene. The resulting organic layer was washed with water, followed by treated with activated charcoal, then filtered through hyflobed and

washed hyflobed with toluene to get filtrate. The resulting filtrate was treated with aqueous sodium dithionite solution (1%) and then organic layer was separated. The resulting organic layer dried over sodium sulphate and concentrated under reduced pressure to get yellow oily liquid. The resulting yellow oil liquid crystallized in acetone to get perphenazine compound of structural formula I.
The perphenazine compound of structural formula I may also purified by the process of recrystallization in ethyl acetate or isopropyl alcohol solvent.
The isolated perphenazine compound of structural formula I may be dried at a temperature in the range of 40°C to 60°C for a period of 30 minutes to 4 hours.
The perphenazine compound of structural formula I contain less than 0.15% of impurity represented by compound of structural formula XXVIII.
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-chloropropyl) piperazin-l-yl) ethanol compound of structural formula XVII.
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 l-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 perphenazine compound of structural formula I. Step-1: Preparation of l-(2-(tert-butyldimethylsilyloxy) ethyl)-4-(3-chloropropyl) piperazine compound of structural formula (XX).
A solution of dihydrochloride salt of 2-(4-(3-chloropropyl) piperazin-1-yl) ethanol compound of structural formula XVII (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 (3 x 1000ml) 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-butyldimethyIsilyloxy) ethyl) piperazin-1-yl) propyl)-2-chloro-10H-phenothiazine compound of structural formula XXI.
A solution of 2-chloro-10H-phenothiazine compound of formula VI (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 (XX) (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 perphenazine compound of structural formula I.
A solution of 10-(3-(4-(2-(tert-butyldimethylsilyloxy) ethyl) piperazin-1-yl) propyl)-2-chloro-lOH-phenothiazine compound of structural formula XXI (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 layers were combined and treated with activated charcoal (50 gm) for 1 hour at 25-30°C and then resulting organic layer was filtered through hyfldbed 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 solid. The resulting solids were recrystallized with acetone and dried at 55-60°C for 1 hour under reduced pressure to get title compound. Yield: 70 gm. Purity: 99.9% (By HPLC) Impurity compound of structural formula XXVIII: less than 0.1%
Example 3: Preparation of perphenazine compound of structural formula I.
Step-1: Preparation of 2-(4-(3-chIoropropyI) piperazin-1-yl) ethyl acetate compound of
structural formula XXIX.
A solution of dihydrochloride salt of 2-(4-(3-chloropropyl) piperazin-1-yl) ethanol compound of structural formula XVII (50 gm) in dichloromethane (250 ml) was added triethylamine (75 ml) and stirred for 1 hour at 20-25 °C. The resulting reaction mixture was filtered and washed with dichloromethane (100 ml) to get filtrate. The resulting filtrate was added triethylamine (75 ml), acetic anhydride (37 ml) and stirred for 4 hours at 25-30°C. The resulting reaction mixture was cooled to 15-25°C, quenched with water (250 ml) and then organic layer was separated. The remaining aqueous layer was extract with dichloromethane (250 ml) and then all organic layers were combined. The resulting organic layer was washed with water (2x100 ml), treated with aqueous sodium bicarbonate solution (2%, 100 ml) for 30 minutes and then organic layer was separated. The resulting organic layer was washed with water (3x200 ml), dried over sodium sulphate and concentrated under reduced pressure to get title compound as yellow oil. Yield: 37 gm.

Step-2: Preparation of 2-(4-(3-(2-chloro-10H-phenothiazin-10-yI) propyl) piperazin-1-yl) ethyl acetate compound of structural formula XXX.
A solution of 2-chloro-10H-phenothiazine compound of formula VI (15 gm) in dimethyl sulfoxide (620 ml) was added potassium tert-butoxide (14.4 gm) and stirred for 1 hour at 25-30°C. The resulting reaction mixture was added solution of 2-(4-(3-chloropropyl) piperazin-1-yl) ethyl acetate compound of structural formula XXIX (32 gm) in dimethyl sulfoxide and stirred for 3 hours at 50-55°C. The resulting reaction mixture was cooled to 20-25°C, quenched with ice cold water (400 ml) and extracted with toluene (2x200 ml) to get organic layer. The resulting organic layer was washed with water (2x200 ml), treated aqueous hydrochloric acid solution (10%, 100 ml) up to pH 1 and then organic layer was separated. The resulting organic layer was extracted with aqueous hydrochloric acid solution (10%, 150 ml) and then aqueous layer was separated. Then all aqueous layers were combined and extracted with toluene (2x200 ml). The remaining aqueous layer was basified with potassium carbonate solution up to pH 8-9 and extracted with toluene (2x100 ml). The resulting organic layer was washed with water (2x200 ml), dried over sodium sulphate and concentrated under reduced pressure to get title compound as brown oily liquid. Yield: 28 gm.
Step-3: Preparation of perphenazine compound of structural formula I.
A solution of 2-(4-(3-(2-chloro-10H-phenothiazin-10-yl) propyl) piperazin-1-yl) ethyl acetate compound of structural formula XXX (28 gm) in methanol (196 ml) was added aqueous sodium hydroxide solution (20%, 75ml) at 20-25°C. The resulting reaction mixture was heated to 50-55°C and stirred for 3 hours. Then the reaction mixture was cooled to 25-30°C, quenched with ice cold water (150 ml) and extracted with toluene (2x150 ml). The resulting organic layer was washed with water (2x100 ml), followed by treated with activated charcoal (4.0 gm) for 1 hour then filtered through hyflobed and hyflobed washed with toluene (50 ml) to get filtrate. The resulting filtrate was added aqueous sodium dithionite solution (1%, 100 ml) and stirred for 20 minutes at 25-30°C. Then organic layer was separated and resulting organic layer was again treated with aqueous sodium dithionite solution (1%, 100 ml) twicely. Then the organic layer was dried over sodium sulphate and concentrated under reduced pressure to get yellow oily

liquid. The resulting yellow oily liquid was added acetone (35 ml) and stirred for 15 minutes at
20-25°C. Then the solution was cooled to 0-5°C and stirred for 2 hours to get solid. The resulting
solids were filtered, washed with chilled acetone (13 ml) and dried at 55-60°C for 1 hour under
reduced pressure to get title compound.
Yield: 9.2 gm
Purity: 99.9% (By HPLC)
Impurity compound of structural formula XXVIII: less than 0.1%

WE CLAIM:
1. An improved process for the preparation of perphenazine compound of structural formula I comprising the steps of:
a. protecting compound of structural formula XVII with protecting agent to get compound of structural formula XVIII,
b. condensing compound of structural formula XVIII with compound of structural formula VI to get compound of structural formula XIX and
c. deprotecting compound of structural formula XIX to get perphenazine compound of structural formula I.
wherein, P is protecting group such as benzyl, tetrahydropyranyl, trityl, trimethylsilyl, tert-butyldimethylsilyl or any other alcohol protecting group.

2. The process according to claim no. 1, wherein the compound of structural formula XVIII is prepared by reacting compound of structural formula XVII or its dihydrochloride salt with protecting agent such as, tert-butyldimethylsilyl chloride, trimethylsilyl chloride, trityl chloride, dihydropyran, acetic anhydride or acetyl chloride in presence of organic base such as, triethylamine, diisopropylamines, imidazole, pyridine, pyridazine, pyrimidine, lithium diisopropylamide, potassium bis(trimethylsilylamide), potassium tert-butoxide, dimethyl amino pyridine, l,8-Diazabicyclo[5.4.0]undec-7-ene (DBU) or 1,5-Diazabicyclo[4.3.0]non-5-ene(DBN) etc. in non-polar organic solvent at a temperature in the range of 20°C to 50°C for a period of 30 minutes to 4 hours.
3. The process according to claim no. 1, wherein the compound of structural formula XIX is prepared by condensing the compound of structural formula XVIII with compound of structural formula VI in presence of organic base such as, triethylamine, diisopropylamines, imidazole, pyridine, pyridazine, pyrimidine, lithium diisopropylamide, potassium bis(trimethylsilylamide), potassium tert-butoxide, dimethyl amino pyridine, l,8-Diazabicyclo[5.4.0]undec-7-ene (DBU) or 1,5-Diazabicyclo[4.3.0]non-5-ene(DBN) etc. in polar aprotic solvent at a temperature in the range of 20°C to 40°C for a period of 1 hour to 14 hours.
4. The process according to claim no. 1, wherein the perphenazine compound of structural formula I is prepared by deprotecting compound of structural formula XIX in presence of inorganic acid in such as, hydrochloric acid, hydrobromic acid, nitric acid, sulfuric acid, phosphoric acid and the like, in polar protic solvent or non-polar organic solvent or mixture thereof at a temperature in the range of 25°C to 50°C for a period of 2 hours to 24 hours.
5. An improved process for the preparation of perphenazine compound of structural formula I comprising the steps of:
a. protecting compound of structural formula XVII with tert-butyldimethylsilyl chloride to get compound of structural formula XX,

b. condensing compound of structural formula XX with compound of structural formula VI to get compound of structural formula XXI and
c. deprotecting compound of structural formula XXI to get perphenazine compound of structural formula I
6. Another aspect of the present invention is to provide an improved process for the preparation of perphenazine compound of structural formula I comprising the steps of: a. protecting compound of structural formula XVII with acetylating agent to get compound of structural formula XXIX,

b. condensing compound of structural formula XXIX with compound of structural formula VI to get compound of structural formula XXX and
c. deprotecting compound of structural formula XXX to get perphenazine compound of structural formula I.
7. The process according to claim no. 6, wherein the compound of structural formula XXIX is prepared by reacting compound of structural formula XVII or its dihydrochloride salt with acetylating agent such as, acetic anhydride or acetyl chloride in presence of organic base such as, triethylamine, diisopropylamines, imidazole, pyridine, pyridazine, pyrimidine, lithium diisopropylamide, potassium bis(trimethylsilylamide), potassium tert-butoxide, dimethyl amino pyridine, l,8-Diazabicyclo[5.4.0]undec-7-ene (DBU) or 1,5-Diazabicyclo[4.3.0]non-5-ene(DBN) etc. in non-polar organic solvent at a temperature in the range of 15°C to 50°C for a period of 30 minutes to 12 hours.
8. The process according to claim no. 6, wherein the compound of structural formula XXX is prepared by condensing the compound of structural formula XXIX with compound of structural formula VI in presence of organic base such as, triethylamine, diisopropylamines, imidazole, pyridine, pyridazine, pyrimidine, lithium

diisopropylamide, potassium bis(trimethylsilylamide), potassium tert-butoxide, dimethyl
amino pyridine, l,8-Diazabicyclo[5.4.0]undec-7-ene (DBU) or 1,5-
Diazabicyclo[4.3.0]non-5-ene(DBN) etc. in polar aprotic solvent at a temperature in the range of 20°C to 60°C for a period of 1 hour to 8 hours.
9. The process according to claim no. 6, wherein the perphenazine compound of structural formula I is prepared by deprotecting compound of structural formula XXX in presence of inorganic base such as, 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. in polar protic solvent at a temperature in the range of 20°C to 70°C for a period of 1 hour to 8 hours.
10. The process according to claim nos. 2, 3, 4, 7, 8 and 9, wherein the non-polar organic solvent is selected from the group consisting of chloroform, dichloromethane, dichloroethane, diethyl ether, methyl tertiary-butyl ether, 1,4-dioxane, toluene, pentane, cyclopentane, hexane, cyclohexane or mixture(s) thereof; The polar aprotic solvent is selected from the group consisting of acetone, acetonitrile, dimethylformamide, dimethyl sulfoxide, ethyl acetate, nitromethane, propylene carbonate, tetrahydrofuran or mixture(s) thereof; The polar protic solvent is selected from the group consisting of methanol, ethanol, n- butanol, isopropanol, n-propanol or mixture(s) thereof.