FORM 2
THE PATENTS ACT, 1970
(39 of 1970)
&
THE PATENTS RULE, 2003
COMPLETE SPECIFICATION
(See section 10 and rule 13)
Title of the invention
"PROCESS FOR THE PREPARATION OF TAPENTADOL AND ITS ACID ADDITION SALTS THEREOF'
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, Pin Code: 400705 India.
1. The following complete specification particularly describes and ascertains the nature of this invention and the manner in which it is to be performed.

PROCESS FOR THE PREPARATION OF TAPENTADOL AND ITS ACID ADDITION SALTS THEREOF
FIELD OF THE INVENTION
The present invention relates to an improved process for the preparation of tapentadol and its acid addition salts thereof. The process comprises converting a compound of structural formula II into tapentadol hydrochloride compound of structural formula I via the formation of an intermediate compound of structural formula III.

BACKGROUND OF THE INVENTION
Tapentadol hydrochloride is chemically 3-[(1R, 2R)-3-(dimethylarnino)-l-ethyl-2-methylpropyl] phenol monohydrochloride and is known from U.S.Reissue Patent No. RE 39, 593 and is represented by compound of structural formula I.


Formula I
Tapentadol hydrochloride is marketed by ORTHO MCNEIL JANSSEN under Proprietary Name "Nucynta" in USA. NUCYNTA is an opioid analgesic indicated for the relief of moderate to severe acute pain in patients 18 years of age or older.
The process disclosed in U.S. Reissue Patent No. RE 39,593 for preparing tapentadol hydrochloride is shown in scheme 2.

PCT Publication nos. 2004/108658 and 2005/000788 describe an alternate process for preparing tapentadol hydrochloride compound of structural formula I, which are incorporated herein by reference only.

U.S. Patent No. 6,380,440 describes a process for the preparation of 3-bromoanisole comprising methoxydenitrating 3-bromonitrobenzene in the presence of phase transfer catalyst.
SUMMARY OF THE INVENTION:
A first aspect of the present invention is to provide a process for preparing tapentadol hydrochloride compound of structural formula I comprising the steps of:
a. reacting compound of structural formula II or its acid addition salts thereof with alkali metal alkoxides to get a compound of structural formula III or its acid addition salts thereof and

IIa, when R =halogen atom P1 = C1-C5 alkyl group
IIb, when R = Nitro group

P1 = C1-C5 alkyl group
b, converting compound of structural formula III or its acid addition salts thereof into tapentadol hydrochloride compound of structural formula I.

A second aspect of the present invention is to provide a process for the preparation of a compound of structural formula II or its acid addition salts thereof comprising the step of:
a. reacting compound of formula VI with dimethylamine or its acid addition salts and paraformaldehyde to get a compound of structural formula VII,

b. resolving compound of formula VII by resolving agent to get a compound of structural formula VIII,

c. reacting compound of structural formula VIII with ethyl magnesium halide to get a mixture of compounds of structural formula IX and IX' and then

d. converting a mixture of compounds of structural formula IX and IX' into a compound of structural formula II or its acid addition salts thereof.


A third aspect of the present invention is to provide a process for the preparation of a compound of structural formula IIb or its acid addition salts thereof comprising the step of:
a. converting compound of structural formula IXb or its acid addition salts into a compound of structural formula X or its acid addition salts and

b. converting compound of structural formula X or its acid addition salts into a compound of structural formula IIb or its acid addition salts thereof.

A fourth aspect of the present invention is to provide a process for the preparation of (2S,3S)-1-dimethylamino-3-(3-nitrophenyl)-2-methylpentan-3-ol compound of structural formula IXb comprising the step of:

a. reacting l-bromo-3-nitro benzene with magnesium and l-dimethylamino-2-
methylpentan-3-one in an organic solvent to get (2RS,3RS)-l-dimethylamino-3-
(3-nitrophenyl)-2-methylpentan-3-ol and
b. separating (2S, 3S}-l-dimethylarnino-3-(3-nitrophenyl)-2-methylpentan-3-ol
from (2RS,3RS)-1-dime1thylamino-3-(3-nitrophenyl)-2-methylpentan-3-ol.
Another aspect of the present invention is to provide following compounds of structural formula II, II', VIII, IX, IX', X and XI useful as an intermediates for the preparation of tapentadol hydrochloride compound of structural formula I.

DETAILED DESCRIPTION OF THE INVENTION:
The reaction of a compound of formula VI with dimethylamine or its acid addition salts and paraformaldehyde may be carried out in the presence of hydrochloric acid in an organic solvent.

The examples of organic solvent may include alcohol and ether solvents.
The examples of alcohol solvents may include methanol, ethanol, propanol, isopropanol, butanol, isobutanol or mixture(s) thereof.
The examples of ether solvents include tetrahydrofuran, 2-methyltetrahydrofuran, dioxane, diethyl ether, diisopropyl ether, dibutyl ether, methyl tertiary butyl ether, dipropyl ether or mixture(s) thereof.
The reaction of a compound of formula VI with dimethyl amine or its acid addition salts and paraformaldehyde may be carried out a temperature in the range of 35°C to 85°C.
The reaction of a compound of formula VI with dimethylamine or its acid addition salts and paraformaldehyde may be carried out for a period of 8 hours to 24 hours.
A compound of structural formula VII may be isolated from the reaction mixture by the combination of steps comprising of centrifugation, washing with ketonic solvents, treating with alkali solution and concentrating under reduced pressure.
The examples of ketone solvents may include acetone, methyl ethyl ketone, isobutyl ketone, methyl isobutyl ketone or mixrure(s) thereof.
The alkali solution is selected from the group comprising of aqueous solution of sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate or sodium bicarbonate.
The concentration of alkali solution may be in the range of 15% wt/wt to 35% wt/wt.

The examples of resolving agent may be selected from the group comprising of L-(-)-dibenzoyi tartaric acid; D-(-)-tartaric acid or hydrates thereof
The resolution of compound of formula VII may be carried out in alcohol solvents, ketone solvents or mixture(s) thereof.
The reaction of a compound of structural formula VIII with ethyl magnesium halide may be carried out in ether solvents.
The examples of ethyl magnesium halide may include ethyl magnesium chloride or ethyl magnesium bromide.

The dehydration of compound of structural formula IX may be carried out in the presence of inorganic acid in an organic solvent.
The compound of structural formula IX may be converted into a compound of structural formula II by dehydration of a compound of structural formula IX by inorganic acid to get a compound of structural formula XI, followed by the hydrogenation of a compound of structural formula XI by catalytic hydrogenation reaction.

The example of inorganic acid may be selected from the group comprising of trifluoroacetic anhydride, trifluoroacetic acid, hydrochloric acid, hydrobromic acid, phosphoric acid, sulfuric acid or mixture(s) thereof.
The example of organic solvent may include polar aprotic solvents.
The examples of polar aprotic solvents may be selected from the group comprising of acetone, methyl isobutyl ketone, tetrahydrofuran, acetonitrile, dibutyl ketone, methyl isopropyl ketone, 2-methyltetrahydrofuran, dioxane, ethyl acetate, tertiary butyl acetate, propyl acetate, isobutyl acetate, isopropyl acetate or mixture(s) thereof.
The hydrogenation of a compound of structural formula XI may be carried out in the presence of metal catalyst selected form the group comprising of palladium, platinum, rhodium, nickel or cobalt.
The hydrogenation of a compound of structural formula XI may be carried out in hydrogen pressure in the range of 1 kilogram to 35 kilogram.
The hydrogenation of a compound of structural formula XI may be carried out in the presence of inorganic acid such as hydrochloric acid or hydrobromic acid in organic solvents.
The example of organic solvents may include alcohol solvents or ketone solvents.
The example of alcohol solvents may include methanol, ethanol, propanol, isopropanol, butanol, isobutanol or mixture(s) thereof.

The example of ketone solvents may include acetone, methyl isobutyl ketone, diisopropyl ketone, dibutyl ketone, methyl ethyl ketone or mixture(s) thereof.
The hydrogenation of a compound of structural formula XI may be carried out at a temperature in the range of 30°C to boiling points of above mentioned organic solvents.
The hydrogenation of a compound of structural formula XI may result into a mixture of (2R, 3R) and (2R, 3S) compounds of structural formula II and II'.

The compound of structural formula II or its acid addition salts thereof may be prepared by reacting a mixture of compounds of structural formula II and II' with inorganic acid in ketone solvents followed by the selective precipitation of acid addition salts of a compound of structural formula II.
The acid addition salts of a compound of structural formula II may be optionally converted into a compound of structural formula II by treating acid addition salts of a compound of structural formula II with an alkali solution.

The examples of alkali solution may include the aqueous solution of sodium hydroxide, potassium hydroxide, sodium carbonate, lithium carbonate, cesium carbonate, lithium hydroxide or potassium carbonate.
The compound of structural formula II or its acid addition salts thereof may be reacted with alkali metal alkoxides in an organic solvent to get a compound of structural formula III
The examples of alkali metal alkoxides may include sodium methoxide, potassium methoxide, sodium ethoxide, potassium tertiary butoxide, sodium tertiary butoxide, sodium tertiary pentoxide or potassium ethoxide.
The examples of organic solvent may include methanol, ethanol, propanol, butanol, isobutanol, pentanol, isopropanol or mixture(s) thereof.
The reaction of a compound of structural formula II or its acid addition salts thereof with alkali metal alkoxides in an organic solvent may be carried out at a temperature in the range of 30°C to 80°C.
The reaction of a compound of structural formula II or its acid addition salts thereof with alkali metal alkoxides in an organic solvent may be carried out for a period of 2 hours to 8 hours.
The compound of structural formula III may be isolated in the form of acid addition salts.
The acid addition salts of a compound of structural formula III may be prepared by reacting compound of structural formula III with inorganic acid in an organic solvent.

The examples of inorganic acid may include hydrochloric acid, hydrobromic acid, phosphoric acid or sulfuric acid,
The inorganic acid may be used as such or it may be used as a solution of inorganic acid in an organic solvents,
The solution of inorganic acid in organic solvents may be prepared by purging inorganic acid gas like hydrochloric acid in an organic solvents like alcohol and chlorinated hydrocarbon solvents.
The examples of organic solvents may include above mentioned alcohol solvents and chlorinated hydrocarbon solvents.
The example of chlorinated hydrocarbon solvents may be selected from the group comprising of methylene chloride, ethylene chloride, carbon tetra chloride, chloroform or mixture(s) thereof.
The reaction of a compound of structural formula II or its acid addition salts thereof with alkali metal alkoxides in an organic solvent, may be carried out in the presence of phase transfer catalyst.
The examples of phase transfer catalyst include tributyl methyl ammonium chloride, tetrabutyl ammonium chloride, tetrabutyl ammonium hydroxide, tetrabutyl ammonium hydrogen sulfate or tetrabutyl ammonium bromide.

The compound of structural formula III or its acid addition salts thereof may be converted into tapentadol hydrochloride compound of structural formula I by methods known in the art such as those described in PCT Publication No. 2008/012047 and U.S. Patent No. RE 39, 593, which are incorporated herein by reference only.
The compound of structural formula IXb or its acid addition salts may be converted into a compound of structural formula X or its acid addition salts thereof by reacting compound of structural formula IXb or its acid addition salts with thionyl chloride.
The compound of structural formula X or its acid addition salts may be isolated as an acid addition salts.
The compound of structural formula X or its acid addition salts thereof may be converted into a compound of structural formula IIb by reacting compound of structural formula X or its acid addition salts thereof with dried zinc chloride and sodium borohydride in ether solvents.
The examples of ether solvents may include diethyl ether, tetrahydrofuran, 2-methyl tetrahydrofuran, dioxane, diisopropyl ether, methyl tertiary butyl ether, dibutyl ether, dipropyl ether or mixture(s) thereof.
The reaction of compound of structural formula X or its acid addition salts thereof with dried zinc chloride and sodium borohydride in ether solvents may be carried out a temperature in the range of 25°C to 40°C for a period of 12 hours to 80 hours.
The compound of structural formula IIb may be isolated as an amine-borane complex, which may be converted into free base by reacting amine-borane complex of compound of structural formula IIb with triphenyl phosphine in alcoholic solvents at a temperature in the range of 40-55°C for a period of 12 hours to 24 hours, followed by

the removing of solvent by distillation to get a residue compound of structural formula IIb.
The residue compound of structural formula IIb may be treated with 5% hydrochloric acid solution, followed by washing the hydrochloric acid phase with ether solvents.
The hydrochloric acid phase may be treated with aqueous alkali solution followed by the extraction of compound of structural formula IIb by halogenated hydrocarbon solvents.
The organic layer, which contains a compound of structural formula IIb may be concentrated under reduced pressure to get a residue compound, which may be crystallized in a ketone solvents such as acetone or 2-butanone.
The compound of structural formula IIb may be isolated as an acid addition salts by reacting compound of structural formula IIb with inorganic acid or trimethylchlorosilane.
The compound of structural formula IIb or its acid addition salts may be dried under reduced pressure at a temperature in the range to 50-55oC for a period of 4 hours to 10 hours.
The reaction of l-bromo-3-nitro benzene with magnesium and l-dimethylamino-2-methylpentan-3-one may be carried out in organic solvents such as ether solvents.
The reaction mixture comprising (2RS,3RS)-l-dimethylamino-3-(3-nitrophenyl)-2-methylpentan-3-ol may be quenched with 20% ammonium chloride solution and then it may be extracted with diethyl ether solvents.

The organic layer containing (2RS, 3RS)-l-dimethylamino-3-(3-nitrophenyl)-2-methylpentan-3-ol may be concentrated under reduced pressure and then resulting residue may be separated by using chiral HPLC technique to get (2S, 3S)-1-dirnethylarnino-3-(3-nitrophenyl)-2-methylpentan-3-ol.
In the following example, the preferred aspects 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 TAPENTADOL HYDROCHLORIDE
Step 1: Synthesis of 3-(dimethylamino)-l-(3-nitro phenyl)-2-methyl-l-propanone (Formula VIIb)
A solution of l-(3-nitro phenyl)-1-propanone (240 gm) in 2-propanol (584 ml) were added dimethylamine hydrochloride (238.3 gm), paraformaldehyde (109.5 gm) and aqueous HC1 solution (26.5 ml). The resulting reaction mixture was refluxed for 8 hours, cooled to 20°C, and then resulting suspension was filtered, washed with acetone (2x100 ml) and then it was dissolved in a mixture of water (730 ml) and toluene (146 ml) and then aqueous NaOH solution (20% wt/wt) was added until a pH value between 10.0 and 10.5 was reached. The organic layer was separated, washed with water and then concentrated under reduced pressure to get a title compound as an oily residue (294.9 gm).
Step 2: Synthesis and isolation of (2S)-3-(dimethylamino)-l-(3-nitro phenyl)-2-methyl-1-propanone (Formula VIIIb)
A solution of 3-(dimethylamino)-l-(3-nitro phenyl)-2-methyl- 1-propanone (114.7 gm) in ethanol (50 ml) were added to a solution of L-(-)-dibenzoyl-tartaric acid monohydrate (188.2 gm) in ethanol (950 ml) .The resulting reaction mixture was stirred at 38°C for 48 hours and then it was cooled to 20°C and then resulting solids were filtered, washed with ethanol (50 ml) and dried at a temperature of 40°C under reduced pressure to get L-(-)-dibenzoyl-tartaric acid salt of (2S)-3-(dimethylamino)-l-(3-nitro phenyl)-2-methyl-1-propanone (207.5 gm).

L-(-)-dibenzoyl-tartaric acid salt of (2S)-3-(dimethylamino)-l-(3-nitro phenyl)-2-methyl-1-propanone (207.5 gm) was suspended in methyl-tert-butyl ether (1050 ml) and then diethyl amine (72.4 ml) was added.
The resulting suspension was stirred at 25°C for 3 hours and then resulting solids were filtered and filtrate was concentrated under reduced pressure to get a title compound as an oily residue (73.9 gm).
Step 3: Synthesis of a mixture of (2S, 3S)-l-(dimethylamino)-3-(3-nitro phenyl)-2-methyl-3-pentanol (IXb) and (2S, 3R)-l-(dimethylarnino)-3-(3-nitro phenyl)-2-methyl-3-pentanol (IXb')
A solution of EtMgCl in THF (242 ml) was stirred and cooled to 2°C. (2S)-3-(dimethylarnino)-l-(3-nitro phenyl)-2-methyl-l-propanone (101.3 gm) was slowly added over a period of 50 minutes while the temperature of reaction mixture was kept below 25°C. The mixture was stirred for 3 hours at 22 °C, and then slowly quenched in a mixture of ice-water (352 ml) and acetic acid (63.9 ml). The mixture was stirred for 30 minutes then NH4OH (98.8 ml) was added and then reaction mixture was allowed to stirred for 10 minutes at 25-30°C. The organic layer was separated, washed with water (44 ml) and concentrated under reduced pressure to get a title compound (113 gm).
Step 4: Synthesis of (2R, 3R)-3-(3-nitro phenyl)-N, N, 2-trimethylpentanamine (IIb)
A solution of compound obtained in step 3, (50.3 g) in 2-methyltetrahydrofuran (120 ml) was added trifluoroacetic anhydride (30.6 ml) at 5°C over a period of 10 minutes. The resulting reaction mixture was stirred for 1 hour at 20°C then palladium [(10 % on activated carbon) (2.52 g)] was added and then resulting reaction mixture was stirred at 3-bar hydrogen pressure for 4 hours at 40°C. The reaction mixture was filtered at 20°C under nitrogen atmosphere. The filtrate was washed with 2-methyltetrahydrofuran (10 ml) and then water (160 ml) and NaOH solution (28.6 ml) was added, organic layer was separated, concentrated under reduced pressure to get title compound as a colorless oily compound (46.10 gm).
Step 5: Synthesis of (2R, 3R)-3-(3-methoxyphenyl)-N, N, 2-trimethylpentanamine monohydrochloride

A solution of compound obtained in step 4 {20gm) in methanol (100 ml) was reacted with sodium methoxide (7.5 gm) at 50°C for 6 hours. The resulting reaction mixture was cooled and then it was treated with isopropanolic hydrochloric acid (4 gm hydrochloric acid dissolved in 20 ml isopropanol) at 0°C and then resulting reaction mixture was stirred for 6 hours at 0-5°C and then resulting solids were filtered to get title compound.
Yield: 18 gm
Step 6: Synthesis of (1R, 2R}-3-(3-dimethylamino-1-ethyl-2-methyl-propyl) phenol hydrochloride (Formula I)
A compound obtained in step 5(15 gm) was dissolved in methane sulfonic acid (60ml) and then methionine (11 gm) was added and then resulting reaction mixture was agitated at 75°C-80°C for 16 hours. The reaction mixture was quenched with water (100ml) and then sodium hydroxide solution (100 ml, 20%wt/wt) and ethyl acetate (100ml) were charged into the reaction mixture. The resulting reaction mixture was stirred at 30°C for 30 minutes then organic layer was separated , washed with water (100 ml) and then it was given a carbon treatment (3 gm) and then it was concentrated under reduced pressure to get a residue compound (14 gm). The residue (14 gm) was dissolved in acetone (75 ml) and then concentrated hydrochloric acid (10 ml) was added and then resulting reaction mixture was stirred for 3 hours at 0-5°C and then isopropanol (100 ml) was added and then resulting reaction mixture was refluxed for 15 minutes and then it was cooled to 0°C to 5°C and then stirred for 3 hours and then resulting solids were filtered to get a title compound.
Yield: 12 gm ; Purity: 100% (By HPLC)

EXAMPLE 2: PREPARATION OF (2R, 3R)-[3-(3-NITRO PHENYL)-2-METHYLPENTYL] - DIMETHYLAMINE HYDROCHLORIDE (FORMULA IIB)
Step 1: Synthesis of (2S, 3S)-[3-chloro-3-(3-nitro phenyl)-2-methylpentyl]-dimethylamine hydrochloride (Formula X)
(2S, 3S)-l-dimethylamino-3-(3-nitro phenyl)-2-methylpentan-3-ol hydrochloride (25gm) was reacted with thionyl chloride (25ml) at 25-30°C for 12 hours then excess thionyl chloride was distilled out under reduced pressure and the resulting residue compound was crystallized from a mixture of diethyl ether (250 ml) and methyl ethyl ketone (50 ml) to get a title compound.
Step 2: Synthesis of (2R, 3R)-[3-(3-nitro phenyl)-2-methyIpentyl] - dimethylamine hydrochloride (Formula IIb)
A solution of compound of formula X (10 gm) in tetrahydrofuran (200 ml) was added zinc borohydride suspension (dried zinc chloride (50 gm) and sodium borohydride (10gm) dissolved in 200 ml diethyl ether) at 25-30°C and then resulting reaction mixture was stirred for 48 hours at 25-30°C and then resulting reaction mixture was added drop-wise to saturated ammonium chloride (100 ml) and then organic layer was separated. The organic layer was concentrated under reduced pressure to get amine-borane complex (8 gm). The amine-borane complex (8 gm) was dissolved in methanol (50 ml) and then triphenyl phosphine (8 gm) was added and then resulting reaction mixture was refluxed for 18 hours. The solvent was distilled off under reduced pressure and the resulting residue compound was treated with 5% hydrochloric acid (100 ml) and then aqueous layer was washed with diethyl ether (2x50ml) and then aqueous layer was basified with 20ml sodium hydroxide solution (15%) and then it was extracted with dichloromethane (50 ml). The organic layer was washed with water (2x50 ml), dried over anhydrous sodium sulfate (10 gm) and then concentrated under reduced pressure to get a residue compound, the residue compound was taken up in methyl ethyl ketone (25 ml) and then it was treated with trimethylchlorosilane / water (7.5 gm in 25 ml water) to get title compound.

WE CLAIM:
1. A process for preparing tapentadol hydrochloride compound of structural formula I comprising the steps of:
a. reacting compound of structural formula II or its acid addition salts thereof with alkali metal alkoxides to get a compound of structural formula III or its acid addition salts thereof and

IIa, when R = halogen atom Pt = C1-C5 alkyl group
IIb, when R = Nitro group
b. converting compound of structural formula III or its acid addition salts thereof into tapentadol hydrochloride compound of structural formula I.

P1= C1-C5 alkyl group
2. The process according to claim 1, wherein alkali metal alkoxides is selected from the group comprising of sodium methoxide, potassium methoxide, sodium ethoxide, potassium tertiary butoxide, sodium tertiary butoxide, sodium tertiary pentoxide or potassium ethoxide.

3. The process according to claim 1, wherein the reaction of a compound of structural formula II or its acid addition salts thereof with alkali metal alkoxides in an organic solvent is carried out in the presence of phase transfer catalyst such as tributyl methyl ammonium chloride, tetrabutyl ammonium chloride, tetrabutyl ammonium hydroxide, tetrabutyl ammonium hydrogen sulfate or tetrabutyl arnmonium bromide.
4. A process for the preparation of a compound of structural formula II or its acid addition salts thereof comprising the step of:
a. reacting compound of formula VI with dimethylamine or its acid addition salts and paraformaldehyde to get a compound of structural formula VII,

Formula VIa, when R = halogen atom Formula VIIa, when R = halogen atom
Formula VIb when R = Nitro group Formula VIIb when R = Nitro group
b. resolving compound of formula VII by resolving agent to get a compound of structural formula VIII,

Formula VIIIa when R = halogen atom
Formula VIIa, when R = halogen atom Formula VIIIb when R = Nitro group
Formula VIIb when R = Nitro group
c. reacting compound of structural formula VIII with ethyl magnesium halide to get a mixture of compounds of structural formula IX and IX' and then


d. converting compounds of structural formula IX and IX' into a compound of structural formula II or its acid addition salts thereof.

Formula IXa, when R = halogen atom Formula IXa, when R = halogen atom IIa, When R = halogen atom
Formula IXb when R = Nitro group Formula IXb when R = Nitro group IIb, When R = Nino group
5. The process according to claim 4, wherein the reaction of a compound of formula VI with dimethylamine or its acid addition salts and paraformaldehyde is carried out in the presence of hydrochloric acid in an organic solvent such as alcohol or ether solvents.
6. The process according to claim 4, wherein the resolving agent is selected from the group comprising of L-(-)-dibenzoyl tartaric acid; D-(-)-tartaric acid or hydrates thereof.
7. A process for the preparation of a compound of structural formula IIb or its acid addition salts thereof comprising the step of:
a. converting compound of structural formula IXb into a compound of structural formula X and


b. converting compound of structural formula X into a compound of structural formula IIb or its acid addition salts thereof.

8. The process according to claim 7, wherein the compound of structural formula IXb is converted into a compound of structural formula X or its acid addition salts thereof by reacting compound of structural formula IXb with thionyl chloride and compound of structural formula X or its acid addition salts thereof may be converted into a compound of structural formula IIb by reacting compound of structural formula X or its acid addition salts thereof with dried zinc chloride and sodium borohydride in ether solvents such as diethyl ether, tetrahydrofuran, 2-methyl tetrahydrofuran, dioxane, diisopropyl ether, methyl tertiary butyl ether, dibutyl ether, dipropyl ether or mixture (s) thereof.
9. A compounds of structural formula II, II', VIII, IX, IX', X and XI useful as an intermediates for the preparation of tapentadol hydrochloride compound of structural formula I.


IIa, when R = halogen atom Formula VIIIa, when R = halogen atom (2S, 3S) II'a, when R = halogen atom
IIb, when R = Nitro group Formula VIIIB when R = Nitro group Formula X III), when R = Nitro group

Formula IXa, when R = halogen atom Formula IXa, when R = halogen atom Formula XIa, when R = halogen atom
Formula IXb when R = Nitro group Formula IXb when R = Nitro group Formula XIb, when R = Nitro group
10. A process for the preparation of (2S,3S)-l-dimethylamino-3-{3-nitrophenyl)-2-methylpentan-3-ol compound of structural formula IXb comprising the step of:
a. reacting l-bromo-3-nitro benzene with magnesium and l-dimethylamino-2-
methylpentan-3-one in an organic solvent to get (2RS,3RS)-l-dimethylamino-3-
(3-nitrophenyl)-2-methylpentan-3-ol and
b. separating (2S, 3S)-l-dimethylamino-3-(3-nitrophenyl)-2-methylpentan-3-ol
from (2RS, 3RS)-l-dimethylamino-3-(3-nitrophenyl)-2-methylpentan-3-ol.