FORM 2
THE PATENTS ACT, 1970
(Act 39 of 1970)
&
THE PATENT RULES, 2003
COMPLETE SPECIFICATION
(See Section 10 & rule 13}
Title: "An improved process for the preparation of
Dexmethylphenidate Hydrochloride"
Name: ZCL Chemicals Limited (An Indian Company)
Address: 'A'- 806/807, 215 Atrium, Chakala, Andheri (East),
Mumbai-400 059, Maharashtra, India.
Nationality: Indian

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
Dexmethylphenidate hydrochloride of formula (A). More particularly, the present invention relates to an improved process for the preparation of Dexmethylphenidate hydrochloride of formula (A) and its intermediate d-threo ritalinic acid hydrochloride of formula (III). Dexmethylphenidate hydrochloride of formula (A) is prepared from d,l-threo ritalinic acid of formula (I) wherein d, 1-threo ritalinic acid is reacted with (-) dibenzoyl-L-tartaric acid to obtain dibenzoyl L-tartrate salt of d-threo ritalinic acid of formula (II). The said tartrate salt of d-threo ritalinic acid of formula (II) is converted into hydrochloride salt of formula (III), d-threo ritalinic acid hydrochloride of formula (III) is reacted with thionyl chloride (SOCI2) in methanol followed by reaction with hydrochloric acid in presence of alcoholic solvent to give Dexmethylphenidate hydrochloride of formula (A).
BACKGROUND OF THE INVENTION
The chemical name of Dexmethylphenidate hydrochloride of formula (A) is (2R)-phenyl-[(2R)-piperidyl-2yl-acetic acid methyl ester hydrochloride and it is also known as Methylphenidate hydrochloride. Methylphenidate hydrochloride is a mixture of d, 1-threo racemates and it is prescribed as psychostimulant. Methylphenidate hydrochloride of formula (A) helps in increasing the activity of Central Nervous System.
Subsequence study of Methylphenidate hydrochloride revealed that its two enantiomers i.e. d,1-threo methylphenidate hydrochloride and d-threo enantiomers are considered to be active and are available in the market to treat Attention Deficient Hyperactivity Disorder (ADHD).
Several methods are reported for the preparation of Dexmethylphenidate hydrochloride of formula (A) by different way of resolution.
US 2507631 has disclosed a process for the preparation of Methylphenidate from a-phenyl-a-pyridyl-(2)-acetonitrile.

US 2838519 and US 2957880 have disclosed a process for preparing bl-antipode of Dexmethylphenidate hydrochloride having specific rotation [a]D22=(+)89° and b2-antipode having specific rotation [a]D22=(-)89°.
US 5936091, US 6359139 and US 6962997 Bl have disclosed a process for resolving piperidyl acetamide stereoisomers using dibenzoyl-D-tartaric acid. Obtained d-threo amide derivative is then forwarded for Dexmethylphenidate hydrochloride.
US 6100401 has disclosed a process for resolution of threo Methylphenidate hydrochloride using dibenzoyl-D-tartaric acid as a resolving agent in presence of base to give Dexmethylphenidate hydrochloride which is further purified to enrich higher optical purity. In the disclosed process, it is necessary to purify the final product to get the pure Dexmethylphenidate hydrochloride.
US 6162919 has disclosed a process for the preparation of d-threo enantiomer of Methylphenidate hydrochloride by using (R)-(-)-l,l'-binaphthyl-2,2'-diyl hydrogen phosphate as a resolving agent, d-threo methylphenidate hydrochloride (Dexmethylphenidate hydrochloride) obtained from the said process is purified in deionized water to enrich a higher optical purity.
US 6242464 Bl has disclosed a resolution process for single enantiomer d or 1-threo methylphenidate which comprises resolution of a mixture of enantiomer using a resolving agent selected from the group consisting of D-and L-O-O' ditoluoyl tartaric acid. ditoluoyl-D-tartrate salt as obtained from the said process is taken for further purification to obtain higher optical purity.
WO 2003/031411 has disclosed a process of direct resolution of racemic threo methylphenidate hydrochloride using di-p-toluoyl-D-tartaric acid and di-p-toluoyl-L-tartaric acid in presence of base to give d and 1 threo methylphenidate hydrochloride respectively.

WO 2008/125914 and US 20080167470 have disclosed a process of enantiomeric resolution of racemic d,l-threo methylphenidate using di-0,0'-aroyl-D-tartaric acid as a resolving agent and tertiary amine as base to prepare chiral acid salt. Basifying the salt to give d-threo methylphenidate freebase and converting into d-threo methylphenidate hydrochloride.
US 2011/0130569 and WO 2010/128517 have disclosed a process for the preparation of d-threo ritalinic acid hydrochloride by resolution of d,l-threo ritalinic acid using (+)dibenzoyl-D-tartaric acid as a resolving agent. Dibenzoyl-D-tartrate salt of d-threo ritalinic acid as obtained above is treated with hydrochloric acid in toluene to isolate the d-threo ritalinic acid hydrochloride and the mother liquor as obtained is treated with hydrochloric acid in toluene and concentrated to isolate the 1-threo ritalinic acid hydrochloride. The main disadvantage of the present invention is that the yield of the final product is less which makes the process industrially not viable.
US 2006/0135777 Al has disclosed a process for the preparation of d-threo methylphenidate hydrochloride by multistep process comprising the conversion of mixture of threo and erythro enantiomer to give racemic threo amide derivative. Resolving the threo amide derivative to its corresponding d-threo enantiomer by using dibenzoyl-D-tartaric acid. Acid hydrolysis of d-threo amide derivative using hydrochloric acid to give d-ritalinic acid hydrochloride followed by reacting it with thionyl chloride in an inert solvent toluene to give acid chloride of d-ritalinic acid which is monitored by HPLC analysis followed by converted to Dexmethylphenidate hydrochloride by methanol . Dexmethylphenidate hydrochloride as obtained with the above method is taken for further purification using deionized water by applying charcoal treatment under hot condition, passing dry hydrogen gas and applying cooling to isolate the pure product of Dexmethylphenidate hydrochloride. The final product yield obtained with the said process is poor and process is lengthy and tedious which makes the process industrially not viable.

There is a need to provide an industrially viable process for the preparation of d-threo ritalinic acid hydrochloride of formula (III) in very good yield and purity which further helps in increasing the yield and purity of the final product i.e. Dexmethylphenidate hydrochloride of formula (A).
The present invention has disclosed a process for the preparation of Dexmethylphenidate hydrochloride of formula (A) in such a way that there is no need of further purification and d-threo ritalinic acid hydrochloride is converted directly into Dexmethylphenidate hydrochloride with a very good yield and higher purity that overcomes the drawbacks of the processes disclosed as above. The disclosed invention is eco-friendly and suits for commercial production as it has less isolation stages.
OBJECTS OF THE INVENTION
The main object of the present invention is to provide an improved process for the preparation of Dexmethylphenidate hydrochloride of formula (A) that obviates the drawbacks of the above processes.
It is also an object of the present invention to provide an improved process for the preparation of Dexmethylphenidate hydrochloride of formula (A) that is industrially viable, cost effective, environment friendly and easy to operate.
It is yet an object of the present invention to provide an improved process for the preparation of Dexmethylphenidate hydrochloride of formula (A) that gives better yield and purity than the prior art processes.
It is yet another object of the present invention to provide a process for
preparing Dexmethylphenidate hydrochloride of formula (A) that comprising
the steps of:
(i) resolving the d,l-threo ritalinic acid of formula (I) by employing
(-)dibenzoyl-L-tartaric acid as a resolving agent in a solvent to obtain
mixture of dibenzoyl-L-tartrate salts of d-threo ritalinic acid of formula
(II) and 1-threo ritalinic acid of formula (V) in a reaction mass;

(ii) filtering the reacting mass to obtain desired dibenzoyl-L-tartrate salt
of d-threo ritalinic acid of formula (II) in mother liquor; (iii) reacting the mother liquor with hydrochloric acid in presence of
solvent to obtain d-threo ritalinic acid hydrochloride of formula (III); (iv) concentrating the reaction mass of step-iii followed by addition of
ketonic solvent to give pure d-threo ritalinic acid hydrochloride of
formula (III); (v) reacting d-threo ritalinic acid hydrochloride of formula (III) with
thionyl chloride in methanol to give Dexmethylphenidate base of
formula (IV); (vi) reacting Dexmethylphenidate base of formula (IV) with hydrochloride
in presence of alcoholic solvent to give Dexmethylphenidate
hydrochloride of formula (A).
It is also an object of the present invention to provide a process for the
preparation of pure d-threo ritalinic acid hydrochloride of formula (III) that
comprising the steps of:
(i) resolving the d,l-threo ritalinic acid of formula (I) by employing
(-)dibenzoyl-L-tartaric acid as a resolving agent in a solvent to obtain
mixture of dibenzoyl-L-tartrate salts of d-threo ritalinic acid of formula
(II) and 1-threo ritalinic acid of formula (V) in a reaction mass;
(ii) filtering the reacting mass to obtain desired dibenzoyl-L-tartrate salt of
d-threo ritalinic acid of formula (II) in mother liquor; (iii) reacting the mother liquor with hydrochloric acid in presence of solvent
to obtain d-threo ritalinic acid hydrochloride of formula (III); (iv) concentrating the reaction mass of step-iii followed by addition of ketonic solvent to give pure d-threo ritalinic acid hydrochloride of formula (III).
It is yet an object of the present invention to provide a single step process for the preparation of Dexmethylphenidate hydrochloride of formula (A) from d-threo ritalinic acid hydrochloride of formula (III) that comprises the steps: (i) reacting d-threo ritalinic acid hydrochloride of formula (III) with thionyl chloride in methanol to give Dexmethylphenidate base of formula (IV);

(ii) reacting Dexmethylphenidate base of formula (IV) with hydrochloric acid in presence of alcoholic solvent to give Dexmethylphenidate hydrochloride of formula (A).
DETAILED DESCRIPTION OF THE INVENTION
The present invention relates to an improved process for the preparation of Dexmethylphenidate hydrochloride of formula (A) and its intermediate d-threo ritalinic acid hydrochloride of formula (III). The present invention also relates to a single step process for the preparation of Dexmethylphenidate hydrochloride of formula (A) from d-threo ritalinic acid of formula (III).
In a preferred embodiment, a process for the preparation of Dexmethylphenidate hydrochloride of formula (A) comprising the following steps: (i) resolving the d,l-threo ritalinic acid of formula (I) by employing
(-)dibenzoyl-L-tartaric acid as a resolving agent in a solvent to obtain
mixture of dibenzoyl-L-tartrate salts of d-threo ritalinic acid of formula
(II) and 1-threo ritalinic acid of formula (V) in a reaction mass; (ii) filtering the reacting mass to obtain desired dibenzoyl-L-tartrate salt
of d-threo ritalinic acid of formula (II) in mother liquor; (iii) reacting the mother liquor with hydrochloric acid in presence of
solvent to obtain d-threo ritalinic acid hydrochloride of formula (III) in
the reaction mass; (iv) concentrating the reaction mass of step-iii followed by addition of
ketonic solvent to give pure d-threo ritalinic acid hydrochloride of
formula (III); (v) reacting d-threo ritalinic acid of formula (III) with thionyl chloride in
methanol to give Dexmethylphenidate base of formula (IV); (vi) reacting Dexmethylphenidate base of formula (IV) with hydrochloride
in presence of alcoholic solvent to give Dexmethylphenidate
hydrochloride of formula (A).
The process for the preparation of Dexmethylphenidate hydrochloride of formula (A) may be shown as per Scheme-1.


Scheme-1:
Now, without limiting the scope of the present invention, the detailed process along with all the possible parameters, reaction conditions may be described as follows:

Step-i & ii:
d,l-threo ritalinic acid of formula (I) is taken for chiral resolution by employing (-)dibenzoyl-L-tartaric acid as a resolving agent in a solvent to obtain mixture of dibenzoyl-L-tartrate salts of d-threo ritalinic acid of formula (II) and 1-threo ritalinic acid of formula (V) in a reaction mass.
Accordingly, an aqueous suspension of d,1-threo ritalinic acid is prepared in a solvent. Solvent is selected 'from lower alkanol such as methanol, ethanol, IPA, butanol or mixture thereof, preferably methanol. Ratio of lower alkanol: water is kept between 15v/w: 16v/w to 18v/w: 20v/w, preferably the ratio is 18v/w: 16v/w.
The said reaction mass is then stirred at a higher temperature to get the clear solution in the reaction mass. Reaction temperature is kept between 50-80°C, preferably 60-80°C. The reaction mass is stirred at the said temperature for 30 minutes 16 hrs. Once the reaction is completed, the reaction mass is cooled gradually to room temperature and then to 5-35°C, preferably to 20-25°C. The reaction mass is stirred at the said temperature fro 1 to 24 hr, preferably 8 hr. The reaction mass is then filtered to remove the undesired product dibenzoyl tartrate salt of 1-threo enantiomer of ritalinic acid of formula (V) and mother liquor kept aside.
Step-iii:
Mother liquor obtained from the filtration of step-i contains dibenzoyl-L-tartrate salt of d-threo ritalinic acid of formula (II) which is further reacted with concentrated aqueous HC1 in a solvent at a 20-25°C.
Step-iv:
The said reaction mass is taken for distillation under reduced pressure to remove water and solvent completely. After completion of distillation, solvent is added in the reaction mass and taken for distillation under reduced pressure to remove the traces of water from the reaction mass. Solvent used in the reaction is selected from toluene or ethyl acetate or mixture thereof.
The reaction mass is cooled to 30 to 55°C and ketonic solvent is added and stirred the same at 30 to 55°C, preferably 50-55°C for 30 min to 4 hr. The

reaction mass is cooled to 0-25°C preferably 15-20°C and stirred for 30 min to 2 hr. Filtered the product and washed with ketonic solvent to give d-threo ritalinic acid hydrochloride of formula (III).
Ketonic solvent used in the reaction is selected from the aliphatic ketones such as acetone, methyl ethyl ketone (MEK) or methyl isobutyl ketone (MIBK) or mixtures thereof.
If desired, d-threo ritalinic acid hydrochloride of formula (III) obtained as above may be taken for purification in methanol as a solvent in which d-threo ritalinic acid hydrochloride of formula (III) is dissolved in methanol, filtered and taken for distillation under reduced pressure to remove methanol. In the said reaction mass, ketonic solvent is added and stirred the same at 40-55°C for 30 min to 1 hr and then at 15-20°C for 1 to 2 hrs. The reaction mass is filtered and washed with ketonic solvent to give pure d-threo ritalinic acid hydrochloride of formula (III).
Ketonic solvent used in the reaction is selected from the aliphatic ketone such as acetone, methyl ethyl ketone (MEK) or methyl isobutyl ketone (MIBK) or mixture thereof.
Undesired traces hthreo ritalinic acid if any present in the reaction mass may be removed through this purification.
The product obtained here is having higher purity and yield than the prior art processes.
Step-v:
In step-v, d-threo ritalinic acid hydrochloride of formula (III) is taken for the preparation of Dexmethylphenidate hydrochloride of formula (A).
The process is a single step process wherein no acid chloride of d-threo ritalinic acid is isolated and it is directly taken for the next step. Isolation of acid chloride product is hazardous and it is difficult to handle the isolated product so the isolation step is eliminated in the present invention and thus

the said process became a cost effective, environment friendly and industrially viable process.
Accordingly, d-threo ritalinic acid hydrochloride of formula (III) is reacted with thionyl chloride in presence of methanol as a solvent at a temperature between 20-70°C, preferably at 50-70°C for 30 min to 8 hr, preferably 2-4 hrs. The reaction mass is taken for distillation under reduced pressure at a temperature between 30°C to 60°C to remove methanol and other low boiling matters like unreacted thionyl chloride. After removal of solvents, water is added and redistilled under reduced pressure to remove the traces of methanol and thionyl chloride from the reaction mass. Reaction mass is then gradually cooled to 0°C to 20°C. Solvent is added and pH of the reaction mass is adjusted ranging 10-13 using aqueous base solution.
Base for adjusting pH of the reaction mass is selected from inorganic bases but not limited to NaOH, KOH or NH4OH. Solvent is selected from dichloro methane (MDC), dichloro ethane (EDC) or chloroform or mixtures thereof. At pH 10-13 product is get dissolved in the said solvent which is further taken for distillation under reduced pressure to give oily mass of Dexmethylphenidate free base of formula (IV).
Step-vi:
To the oily mass of Dexmethylphenidate free base of formula (IV), alcoholic solvent is added and the said reaction mixture is cooled to 0°C to 10°C. Hydrochloric acid is added into it at 0°C to 10°C to give Dexmethylphenidate hydrochloride of formula (A).
Hydrochloric acid used in the reaction may be obtained in any form selected from HC1 gas dissolved in alcoholic solvent, concentrated aqueous HC1, HC1 gas, Preferably IPA.HC1 or HC1 gas is used in the reaction. Alcoholic solvent used in the reaction is selected from IPA or butanol or mixture thereof. The reaction apparatus may be set up according to the requirement which is known in prior art.
After completion of the reaction, reaction mass is filtered and washed with alcohol used in the reaction- to give white crystalline Dexmethylphenidate

hydrochloride of formula (A). The product obtained with the above process is having purity of more than 99.50% as compared to processes reported in the prior art. Further, there is no requirement of purification throughout the process.
In a further embodiment, present invention provides a process for the
preparation of pure d-threo ritalinic acid hydrochloride of formula (III) that
comprises the steps of:
(i) resolving the d,l-threo ritalinic acid of formula (I) by employing
(-)dibenzoyl-L-tartaric acid as a resolving agent in a solvent to obtain
mixture of dibenzoyl-L-tartrate salts of d-threo ritalinic acid of formula
(II) and 1-threo ritalinic acid of formula (V) in a reaction mass;
(ii) filtering the reacting mass to obtain desired dibenzoyl-L-tartrate salt
of d-threo ritalinic acid of formula (II) in mother liquor; (iii) reacting the mother liquor with hydrochloric acid in presence of
solvent to obtain d-threo ritalinic acid hydrochloride of formula (III); (iv) concentrating the reaction mass of step-iii followed by addition of ketonic solvent to give pure d-threo ritalinic acid hydrochloride of formula (HI).
The steps (i) to (iv) of the above process are similar to the steps (i) to (iv) of the process for the preparation of Dexmethylphenidate Hydrochloride of formula (A). d-threo ritalinic acid hydrochloride of formula (III) is obtained in a very good yield and purity which further helps in improving the overall yield of the final product Dexmethylphenidate hydrochloride of formula (A).
Yet in a further embodiment, present invention also provides a single step process for the preparation of Dexmethylphenidate hydrochloride of formula (A) from d-threo ritalinic acid hydrochloride of formula (III) that comprises the steps: (i) reacting d-threo ritalinic acid hydrochloride of formula (III) with thionyl
chloride in methanol to give Dexmethylphenidate base of formula (IV); (ii) reacting Dexmethylphenidate base of formula (IV) with hydrochloric acid in presence of alcoholic solvent to give Dexmethylphenidate hydrochloride of formula (A).

Steps (i) to (ii) of the above process are similar to the steps (v) to (vi) of the process for the preparation of Dexmethylphenidate Hydrochloride of formula (A) simultaneously.
The product obtained with the above process is having purity of more than 99.50% as compared to processes reported in the prior art. Further, there is no requirement of purification throughout the process.
In a similar manner, 1-threo methylphenidate hydrochloride is prepared from undesired Dibenzoyl tartrate salt of 1-threo ritalinic acid of formula (V).
Further details of the present invention will be apparent from the examples presented below. The examples are for purpose of illustration only and are not limited to the particular embodiments illustrated here in.
EXAMPLES
Example 1: Preparation of d-threo ritalinic acid hydrochloride of
formula (III):
d,l-Threo ritalinic acid (I) (100 gm) was charged in the mixture of methanol (15v/w) and water (16v/w) under stirring. (-)Dibenzoyl-L-tartaric acid (182 gm) was dissolved in methanol (3v/w), filtered and added in the reaction mass at 25-30°C within 15-20 min. The resulting mass was heated to reflux temperature at 75-80°C and maintained for 2 hr. The mass was then gradually cooled to 20-25°C within 1-2 hr and maintained for 8 hr. The precipitated material was filtered and washed with 200 ml of methanol: water (1:1) to yield 132 gm of undesired dibenzoyl-L-tartrate salt of 1-threo ritalinic acid of formula (V) having melting point: 92-98°C; SOR [O]D2O: (-)90.0° (C=1.0% w/v in methanol).
To the obtained mother liquor, toluene (225 ml, 2.25v/w) and concentrated 33% aqueous HC1 (40 gm, 30-35%) were added and distilled off at 60-70°C under reduced pressure completely till semisolid residue remains. To remove traces of water, toluene stripping (100mlx2) is done at 60-70°C and degasses it under reduced pressure. Acetone (300 ml) was added in the residue at 50-55°C within 20-30 min and maintained the temperature for 30 min. The reaction mass was cooled to ambient temperature followed by 0-

10°C and maintained for 1 hr. The precipitated crystals were filtered off and
washed with acetone (100 ml, lv/w) to yield 51 gm of desired d-threo
ritalinic acid hydrochloride of formula (III).
Results:
%Yield: 88%
Melting Point: 220-224°C
SOR [a] D20: +90.0° (C=2.0% w/v in methanol)
Purity by HPLC: >99%
Chiral purity: >99.5%
Example 2: Preparation of Dexmethylphenidate hydrochloride of formula (A):
To a solution of d-threo ritalinic acid hydrochloride of formula (III) (40 gm, 0.1564 mole) in methanol (200 ml, 5v/w), thionyl chloride (40 gm, 0.3362 mole) was added within 1 hr by maintaining the temperature 0-10°C. subsequently, the reaction mass was heated to reflux at 65-70cC for 4 hr. Excess methanol and low boilers were then distilled off under reduced pressure; water (80 ml, 2v/w) was added and degassed traces of methanol below 50°C. Resulting mass was then cooled to 20-25°C and added water (400 ml, lOv/w), further cooled to 0-10°C. Dexmethylphenidate free base of formula (IV) was extracted in methylene dichloride (200 ml, 5v/w) at a pH 10-13 using 10% aqueous solution of NaOH below 10CC. Second extraction of methylene dichloride (120 ml, 3v/w) was applied, then combined both organic mass and followed by water wash (240 ml, 6v/w) below 10°C. Separated organic layer was distilled off completely at 40-45°C under reduced pressure. The obtained oily mass is free base of Dexmethylphenidate was dissolved in isopropyl alcohol (160 ml, 4v/w) and cooled to 0-10°C. Hydrochloric acid 23.64% solution in isopropyl alcohol (36.4 gm, 0.2357 mole) was added in the reaction mass slowly within 1 hr by maintaining temperature 0-10°C. After addition completed, temperature raised to 20-25°C and allowed it to stir for 2-3 hr subsequently maintained to 0-10°C for 1 hr. The precipitated solid was then filtered off under suction and washed with chilled isopropyl alcohol (40 ml, lv/w, 10-15°C) of 10-

15°C, dried at 50-60°C to get 37 gm of desired pure Dexmethylphenidate
hydrochloride of formula (A).
Results:
%Yield: 88%
Melting Point: 206-212°C
SOR [a] D20: +88.0° (C=1.0% w/v in methanol)
Purity by HPLC: >99.50%
Chiral purity: >99.5%

We claim:
1. A process for preparing Dexmethylphenidate hydrochloride of formula (A)
comprising the steps of:
(i) resolving the d,l-threo ritalinic acid of formula (I) by employing
(-)dibenzoyl-L-tartaric acid as a resolving agent in a solvent to obtain
mixture of dibenzoyl-L-tartrate salts of d-threo ritalinic acid of formula
(II) and 1-threo ritalinic acid of formula (V) in a reaction mass; (ii) filtering the reacting mass to obtain desired dibenzoyl-L-tartrate salt
of d-threo ritalinic acid of formula (II) in mother liquor; (iii) reacting the dibenzoyl-L-tartrate salt of d-threo ritalinic acid of
formula (II) of step-ii with concentrated aqueous hydrochloric acid in
presence of solvent to obtain d-threo ritalinic acid hydrochloride of
formula (III); (iv) concentrating the reaction mass of step-iii followed by treatment with
ketonic solvent to give pure d-threo ritalinic acid hydrochloride of
formula (III); (v) reacting d-threo ritalinic acid hydrochloride of formula (III) with
thionyl chloride in methanol to give Dexmethylphenidate base of
formula (IV); (vi) reacting Dexmethylphenidate base of formula (IV) with hydrochloric
acid in presence of alcoholic solvent to give Dexmethylphenidate
hydrochloride of formula (A).
2. The process as claimed in claim-1 wherein in step-i, solvent is a mixture of water and lower alcohol.
3. The process as claimed in claim-2 wherein lower alcohol is selected from methanol, ethanol, isopropanol, butanol or mixture thereof.
4. The process as claimed in claim-2 wherein the ratio of lower alcohol: water is between 15v/w:16v/w to 18v/w:20v/w, preferably 18v/w:16v/w.
5. The process as claimed in claim-1 wherein in step-iii, solvent used in the reaction is selected from toluene, ethyl acetate of mixture thereof.
6. The process as claimed in claim-1 wherein in step-iv, ketonic solvent is added at a temperature ranging 40-55°C.

7. The process as claimed in claim-1 wherein in step-iv, ketonic solvent is selected from aliphatic ketones such as acetone, methyl ethyl ketone (MEK), methyl isobutyl ketone (MIBK) or mixture thereof.
8. The process as claimed in claim-1 wherein in step-v, Dexmethylphenidate base of formula (IV) is isolated at pH ranging 10-13 with addition of aqueous base solution.
9. The process as claimed in claim-8 wherein base is selected from inorganic bases like NaOH, KOH, and NH40H.

10. The process as claimed in claim-1 wherein in step-vi, hydrochloride (HC1) is used in the form of HC1 gas dissolved in alcoholic solvent, concentrated aqueous HO, HC1 gas, preferably IPA.HCl or HC1 gas.
11. The process as claimed in claim-1 and claim-10 wherein alcoholic solvent is selected from isopropanol, butanol or mixture thereof.
12. A process for the preparation of pure d-threo ritalinic acid hydrochloride
of formula (III) comprising the steps of:
(i) resolving the d,l-threo ritalinic acid of formula (I) by employing (-)dibenzoyl-L-tartaric acid as a resolving agent in a solvent to obtain mixture of dibenzoyl-L-tartrate salts of d-threo ritalinic acid of formula (II) and 1-threo ritalinic acid of formula (V) in a reaction mass;
(ii) filtering the reacting mass to obtain desired dibenzoyl-L-tartrate salt of d-threo ritalinic acid of formula (II) in mother liquor;
(iii) reacting the mother liquor with hydrochloric acid in presence of solvent to obtain d-threo ritalinic acid hydrochloride of formula (III);
(iv) concentrating the reaction mass of step-iii followed by addition of ketonic solvent to give pure d-threo ritalinic acid hydrochloride of formula (III).
13. The process as claimed in claim-12 wherein in step-i, solvent is a mixture of water and lower alcohol.
14. The process as claimed in claim-13 wherein lower alcohol is selected from methanol, ethanol, isopropanol, butanol or mixture thereof.
15. The process as claimed in claims-13 wherein the ratio of lower alcohol: water is between 15v/w:16v/w to 18v/w:20v/w, preferably 18v/w:16v/w.
16. The process as claimed in claim-12 wherein in step-iii, solvent used in the reaction is selected from toluene, ethyl acetate of mixture thereof.

17. The process as claimed in claim-12 wherein in step-iv, ketonic solvent is selected from aliphatic ketones such as acetone, methyl ethyl ketone (MEK), methyl isobutyl ketone (MIBK) or mixture thereof.
18. The process as claimed in claim-12 wherein in step-iv, ketonic solvent is added at a temperature ranging 40-55°C.
19. A single step process for the preparation of Dexmethylphenidate
hydrochloride of formula (A) from d-threo ritalinic acid hydrochloride of
formula (III) comprising the steps:
(i) reacting d-threo ritalinic acid hydrochloride of formula (III) with thionyl
chloride in methanol to give Dexmethylphenidate base of formula (IV); (ii) reacting Dexmethylphenidate base of formula (IV) with hydrochloride (HC1) in presence of alcoholic solvent to give Dexmethylphenidate hydrochloride of formula (A). 20.The process as claimed in claim-19 wherein in step-i, Dexmethylphenidate base of formula (IV) is generated in the reaction mass at pH between 10-13 with addition of aqueous base solution.
21. The process as claimed in claim-19 wherein base is selected from
inorganic bases such as NaOH, KOH, and NH40H.
22. The process as claimed in claim-19 wherein hydrochloride (HC1) is used in the form of HC1 gas dissolved in alcoholic solvent, concentrated aqueous HC1, HC1 gas.
23. The process as claimed in claims-19 85 22 wherein alcoholic solvent is selected from isopropanol, butanol or mixture thereof.
24. The process as claimed in claim-23 wherein hydrochloride (HC1) is IPA.HC1 or concentrated aqueous HC1.