Field of the Invention:
The present invention relates to novel salts of ethyl (3R,4S,5R)-4,5-imino-3-(l-ethylpropoxy)-l-cyclohexene-l-carboxylate compounds of formula-3, and an improved process for their preparation. Ethyl (3R,4S,5R)-4,5-imino-3-(l-ethylpropoxy)-l-cyclo hexene-1-carboxylate is a key intermediate in the synthesis of oseltamivir phosphate compound of formula-la. Oseltamivir phosphate is chemically known as (3R,4R,5S)-4-(acetyl amino)-5-amino-3-(l-ethylpropoxy)-l-cyclohexene-l-carboxylic acid ethyl ester phosphate and is represented by the structural formula-la

Oseltamivir and in particular its phosphate salt, is a potent inhibitor of neuraminidase and is currently the best drug among the currently available anti-influenza treatments due to its good bioavailability and tolerance. It acts to minimize the effects of flu by inhibiting the protein neuraminidase that lives on the flu virus cells. Oseltamivir developed by Gilead Sciences, and it is currently marketed by Hoffman La Roche under the brand name Tamiflu.
Background of the Invention:
There are various number of synthetic processes for the preparation of Oseltamivir and its pharmaceutically acceptable salts which have been disclosed in the literature, for example US 5763483, US 5952375, Journal of Organic Chemistry 63, 13, 1998; Journal of American Chemical Society 115, 4, 1997, 681; Organic Process Research & Development, 1999, 3, 266-274.
Ethyl (3R,4S,5R)-4,5-imino-3-( 1 -ethylpropoxy)-1 -cyclohexene-1 -carboxylate compound of formula-2 having the following structural formula is a key intermediate compound in the synthesis of Oseltamivir phosphate.
2


COOC2H5

Formula-2 As per the prior art processes, the said intermediate compound of formula-2 is not isolated and is obtained as an oil/residue and used to proceed further. The purity of the intermediate compound of formula-2 obtained as per the prior art is not satisfactory. As the said intermediate is an oily residue, it is not possible to purify the intermediate and there is no specific process disclosed for its purification. In any synthetic process of Active Pharmaceutical Ingredients, it is important to obtain each intermediate product with high purity, to ensure the process provides final Active Pharmaceutical Ingredient with high purity and greater yields and conforms to ICH specifications. It should also avoid the number of purifications in final stages. Hence there is a need in the art to isolate 'and purify the intermediate compounds especially the intermediate compound of formula-2, a key intermediate in the process for important drug like oseltamivir, which may provide substantial advantage both economically as well as quality wise.
In prior art processes, oseltamivir is obtained by the reduction of (3R,4R,5S)-ethyl-4-acetamido-5-azido-3-(pentan-3yl-oxy)cyclohex-l-ene carboxylate compound of formula-4 having the following structure


COOR

Formula-4 They involve the usage of hydrogen gas in presence of catalyst like Palladium on Carbon or Lindlar's catalyst. The usage of Lindlar's catalyst in the prior art process led to high level of impurity formation resulting in low yields.

The present invention provides a process for the reduction of compound of formula-4 with ffigh purity and high yields, which proves to be highly advantageous to get the final product with high quality and yields making the process more economical.
Brief Description of the Invention:
The first aspect of the present invention is to provide novel salts of ethyl (3R,4S,5R)-4,5-imino-3-(l-ethylpropoxy)-l-cyclohexene-l-carboxylate, compounds of general formula-3.
The second aspect of the present invention is to provide a process for the
preparation of novel sahs of ethyl (3R,4S,5R)-4,5-imino-3-(l-ethylpropoxy)-l-
cyclohexene-1-carboxylate, compounds of general formula-3, which comprises of
treating the crude ethyl (3R,4S,5R)-4,5-imino-3-(l-ethylpropoxy)-l-cyclohexene-l-
carboxylate compound of formula-2 with a suitable acid in a suitable solvent to provide
the corresponding acid salt of ethyl (3R,4S,5R)-4,5-imino-3-(l -ethylpropoxy)-
1-cyclohexene-l-carboxylate compounds of formula-3.
The third aspect of the present invention is to provide a process for the preparation of novel salts of ethyl (3R,4S,5R)-4,5-imino-3-(l-ethylpropoxy)-l-cyclohexene-1-carboxylate compounds of formula-3, which comprises of reacting ethyl-(3R,4S,5R)-5-azido-4-hydroxy-3 -(1 -ethylpropoxy)cyclohex-1 -ene carboxylate compound of formula-5 with triphenyl phosphine in a suitable solvent, followed by treatment with a suitable acid to provide the corresponding acid salt of ethyl (3R,4S,5R)-4,5-imino-3-(l-ethylpropoxy)-1 -cyclohexene-1 -carboxylate.
The fourth aspect of the present invention is to provide a crystalline oxalate salt of ethyl (3R,4S,5R)-4,5-imino-3-(l-ethylpropoxy)-l-cyclohexene-l-carboxylate compound of formula-3a.
The fifth aspect of the present invention is to provide a process for the preparation of crystalline oxalate salt of ethyl (3R,4S,5R)-4,5-imino-3-(l-ethylpropoxy)-l-cyclohexene -1 -carboxylate compound of formula-3 a.

The sixth aspect of the present invention is to provide a process for the preparation of oseltamivir compound of formula-1, which comprises of reducing ethyl (3R,4R,5S)-4-acetamido-5-azido-3-(l-ethylpropoxy) cyclohexy-l-ene-1-carboxylate compound of formula-4 in presence of zinc and ammonium chloride in a suitable solvent to provide the oseltamivir compound of formula-1.
The seventh aspect of the present invention is to provide a process for the preparation of oseltamivir compound of formula-1, which comprises of reducing ethyl (3R,4R,5S)-4-acetamido-5-azido-3-(l-ethylpropoxy)cyclohexy-l-ene-l-carboxylate compound of formula-4 in presence of cobalt ion, a ligand and a reducing agent in a suitable solvent to provide the oseltamivir compound of formula-1.
Advantages of the Present Invention:
• Provides novel salts of ethyl (3R,4S,5R)-4,5-imino-3-(l-ethylpropoxy)-l-cyclohexene-1-carboxylate, compounds of general formula-3 having high purity.
• Provides novel oxalate salt of ethyl (3R,4S,5R)-4,5-imino-3-(l-ethylpropoxy)-l-cyclohexene-1-carboxylate compound of formula-3 a.
• Provides an improved process for the reduction of compound of formula-4, providing product with high purity and greater yield.
• A process which is eco-friendly, efficient and commercially viable.
Detailed Description of the Invention:
The present invention relates to novel salts of ethyl (3R,4S,5R)-4,5-imino-3-(l-ethylpropoxy)-l-cyclohexene-l-carboxylate, compounds of formula-3, which is a key intermediate in the preparation of oseltamivir phosphate compound of formula-la.

COOC2H5
i . H3PO4 NH2
Formula-la

As used here in the term "alcoholic solvent" is selected from methanol, ethanol, isopropanol, n-propanol, butanol and the like; the term "ester solvents" refers to ethyl acetate, methyl acetate, n-butyl acetate, isobutyl acetate, sec-butyl acetate, isopropyl acetate and the like; the term "hydrocarbon solvents" refers to toluene, xylene, cyclohexane, hexane, heptane and the like; the term "chloro solvents" refers to methylene chloride, ethylene dichloride, carbon tetra chloride, chloroform and the like; polar aprortic solvents refers to dimethylformamide, dimethylacetamide, dimethyl sulfoxide, tetrahydrofuran and the like; the term "nitrile solvents" refers to acetonitrile and the like; the term "polar solvent" refers to water and the like.
As used here in the term "crude" refers to the compound obtained directly after the reaction or the compound before purification.
The first aspect of the present invention provides novel salts of ethyl (3R,4S,5R)-4,5-imino-3-(l-ethylpropoxy)-l-cyclohexene-l-carboxylate, compounds of general formula-3 represented by the following general formula-3.

COOC2H5 .Acid
Formula-3 wherein "Acid" is a acid which are capable of forming acid addition salt with ethyl (3R,4S,5R)-4,5-imino-3-(l-ethylpropoxy)-!-cyclohexene-1 -carboxylate, compound of formula-2 also known as "aziridine intermediate". The acid is selected from oxalic acid, succinic acid, fumaric acid, malonic acid, malic acid, maleic acid, tartaric acid, citric acid, methanesulfonic acid, paratoluene sulfonic acid, acetic acid, sulfuric acid, phosphoric acid and hydrohalic acid.
As per the prior art the fi^ee base of the compound of formula-3 i.e., ethyl (3R,4S,5R)-4,5-imino-3 -(1 -ethylpropoxy)-1 -cyclohexene-1 -carboxylate compound of formula-2 is not isolated and obtained as an oil with a purity of approximately 60-65%. When this crude with a purity of 60-65% is used to proceed further into subsequent

stages, it will lead to decrease in yield and purity of the consecutive stages and will require a number of purifications to get the desired purity at the final stage.
The novel salts of ethyl (3R,4S,5R)-4,5-imino-3-(l-ethylpropoxy)-l-cyclohexene-I-carboxylate, compounds of general formula-3 of the present invention are having high purity of greater than 98%. The same have been utilized in the process for the preparation of the oseltamivir or its pharmaceutically acceptable salts provides high yields and purity, at the same time avoiding the numerous recrystallizations in final and intermediate stages to get the desired purity set by ICH.
The second aspect of the present invention provides a process for the preparation of novel salts of ethyl (3R,4S,5R)-4,5-imino-3-(l-ethylpropoxy)-l-cyclohexene-l-carboxylate, compounds of general formula-3,

COOC2H5 .Acid
Formula-3 Where in R and an acid is as defined as above,
which comprises of treating the crude ethyl (3R,4S,5R)-4,5-imino-3-(l-ethylpropoxy)-l-cyclohexene-1-carboxylate, compound of formula-2


COOC2H5

Formula-2 with a suitable acid selected from the acids defined above, in a suitable solvent selected from alcohols, ketones, esters, hydrocarbons, polaraprotic solvents, polar solvents, chloro solvents, nitriles or mixtures thereof to provide the corresponding acid salt of ethyl (3R,4S,5R)-4,5-imino-3-(l-ethylpropoxy)-l-cyclohexene-l-carboxylate.

The third aspect of the present invention provides a process for the preparation novel salts of ethyl (3R,4S,5R)-4,5-imino-3-(l-ethylpropoxy)-l-cyclohexene-l-carboxylate, compounds of general formula-3.

Formula-3 which comprises of reacting ethyl (3R,4S,5R)-5-azido-4-hydroxy-3-(l-ethylpropoxy) cyclohex-1-ene-l-carboxylate compound of formula-5.


COOC2H5
N3 Formula-5 with triphenyl phosphine, in a suitable solvent selected from polar aprotic solvent or nitrile solvent, followed by treatment with a suitable acid selected from the above defined acids, in a suitable solvent selected from alcohols, ketones, esters, hydrocarbons, polaraprotic solvents, polar solvents, chloro solvents, nitriles or mixtures thereof, to provide the corresponding acid addition salts of ethyl (3R,4S,5R)-4,5-imino-3-(l-ethylpropoxy)-1-cyclohexene-1-carboxylate.
The fourth aspect of the present invention provides a novel oxalate salt of ethyl (3R,4S,5R)-4,5-imino-3-(l -ethylpropoxy)-!-cyclohexene-1-carboxylate, compound of formula-3a having the following structure.

HN^

o

Formula-3 a

The novel oxalate salt of the present invention is characterized by its DSC which shows two endothermic peaks at 78° C and 141° C. The novel oxalate salt of the present invention is used to prepare highly pure ethyl (3R,4S,5R)-4,5-imino-3-(l-ethylpropoxy)-1-cyclohexene-l-carboxylate compound of formula-2. and high pure oseltamivir phosphate compound of formula-la.
The fifth aspect of present invention provides a process for the preparation of oxalate salt of ethyl (3R,4S,5R)-4,5-imino-3-(l-ethylpropoxy)-l-cyclohexene-l-carboxylate compound of formula-3a having the following structure.
^< o
HN'
Formula-3a which comprises of treating the crude ethyl (3R,4S,5R)-4,5-imino-3-(l-ethylpropoxy)-l-cyclohexene-1-carboxylate compound of formula-2


COOC2H5

Formula-2 with oxalic acid in a suitable solvent selected from alcohols, ketones, esters, hydrocarbons, polaraprotic solvents, polar solvents, chloro solvents, nitriles or mixtures thereof, to provide the oxalic acid salt of ethyl (3R,4S,5R)-4,5-imino-3-(l-ethylpropoxy)-1-cyclohexene-1-carboxylate.
In a preferred embodiment of the present invention, a process for the preparation of oxalate sak of ethyl (3R,4S,5R)-4,5-imino-3-(l-ethylpropoxy)-l-cyclohexene-l-carboxylate compound of formula-3a, comprises of treating the crude ethyl (3R,4S,5R)-4,5-imino-3-(l -ethylpropoxy)-1 -cyclohexene-1 -carboxylate compound of formula-2


COOC2H5

Formula-2 with oxalic acid in a suitable ester solvent preferably ethyl acetate to provide the oxalic acid salt of ethyl (3R,4S,5R)-4,5-imino-3-(l-ethylpropoxy)-l-cyclohexene-l-carboxylate compoimd of formula-3a.
The sixth aspect of the present invention provides a process for the preparation of oseltamivir compound of formula-1,

O'
Formula-1 which comprises of reducing ethyl (3R,4R,5S)-4-acetamido-5-azido-3-(l-ethyl propoxy)cyclohexy-l-ene carboxylate, compound of formula-4

COOC2H5
O'
Formula-4 in presence of zinc dust and ammonium chloride in a suitable solvent selected from alcohols, ketones, esters, hydrocarbons, polar aprotic solvents, polar solvents, chloro solvents, nitriles or mixtures thereof to provide the oseltamivir compound of formula-1. Optionally converting the oseltamivir compound formula-1 into its pharmaceutically acceptable salts, especially phosphate salt of formula-la by conventional methods.

10

In the prior art processes, reduction involves the usage of hydrogen gas in presence of Lindlar's catalyst. The usage of Lindlar's catalyst will leads to the formation of impurity, herein designated as "dihydro impurity" which is having the following structural formula

Dihydro Impurity at the level of more than 30% along with the oseltamivir. The said impurity is observed at the RRT of 0.85. In order to remove this impurity the prior art processes carried out number of purifications at the final stages. The usage of Zinc dust and ammonium chloride for the said reduction avoids the formation of dihydro impurity and hence the number of purifications are not necessary at final steps makes the present process highly advantageous over the prior art.
In a preferred embodiment of the above aspect, a process for the preparation of oseltamivir compound of formula-1,

,rr

COOC2H5

Formula-1 which comprises of reducing ethyl (3R,4R,5S)-4-acetamido-5-azido-3-(l-ethyl propoxy)cyclohexy-l-ene-l-carboxylate, compound of formula-4
11


L'CXX^2H5
HN O'
.A. ^3
Formula-4 in presence of zinc dust and ammonium chloride in a suitable alcoholic solvents preferably isopropyl alcohol and water, followed by isolating the oseltamivir compound of formula-1 from a suitable chloro solvent preferably methylene chloride.
The seventh aspect of the present invention provides a process for the preparation of oseltamivir compound of formula-1,
Formula-1 comprises of reducing ethyl (3R,4R,5S)-4-acetamido-5-azido-3-(l-ethylpropoxy) cyclohexy-l-ene-l-carboxylate, compound of formula-4

o
Formula-4
in the presence of cobalt ion, a ligand and a reducing agent;
wherein the cobalt ion is selected from the group consisting of cobaltous chloride,
cobaltous diacetate and cobaltic chloride; and the ligand is selected from the group
consisting of dimethylglyoxime, 2,2'-bipyridyl and 1,10-phenathroline; the reducing
agent is selected from the group consisting of sodium borohydride, potassium
borohydride, lithium borohydride, tetraalkyl ammonium borohydride and zinc
borohydride in a suitable solvent selected from alcohols, ketones, esters, hydrocarbons.

12

polar aprotic solvents, polar solvents, chloro solvents, nitriles or mixtures thereof; to provide the oseltamivir compound of formula-1.
In a preferred embodiment of the above aspect of the present invention, a process for the preparation of oseltamivir compoimd of formula-1,
Formula-1 comprises of reducing ethyl (3R,4R,5S)-4-acetamido-5-azido-3-(l-ethylpropoxy) cyclohexy-1-ene-l-carboxylate, compound of formula-4


CCXX^2*^5

Fonnula-4 in presence of cobalt ion, a ligand and a reducing agent
wherein the cobalt ion is cobaltous chloride and the ligand is dimethylglyoxime and the reducing agent is sodium borohydride in methanol to provide the oseltamivir compound of formula-1.
Ethyl(3R,4R,5S)-4-acetamido-5-azido-3-(l-ethylpropoxy)cyclohexy-l-ene-l-carboxylate compound of formula-4 and ethyl (3R,4S,5R)-5-azido-4-hydroxy-3-(l-ethylpropoxy) cyclohex-l-ene-l-carboxylate, compound of formula-5 can be readily prepared as per the process disclosed in US 5952375 or by the process known in the art.
The present invention also provides novel salts of alkyl (3R,4S,5R)-4,5-imino-3-(1-ethylpropoxy)-1-cyclohexene-l-carboxylate having the following structural formula
13


COOR

Where in R is an C1-C4 alkyl,
wherein "Acid" is a acid which are capable of forming acid addition salt with alkyl (3R,4S,5R)-4,5-imino-3-(l-ethylpropoxy)-1 -cyclohexene-1 -carboxylate, compound of formula-2 also known as "aziridine intermediate". The acid is selected from oxalic acid, succinic acid, fumaric acid, malonic acid, malic acid, maleic acid, tartaric acid, citric acid, methanesulfonic acid, paratoluene sulfonic acid, acetic acid, sulfuric acid, phosphoric acid and hydrohalic acid.
The related substance of oseltamivir and its pharmaceutically acceptable salts as well as its intermediates were analyzed by HPLC using the following conditions: Column: Inertsil 0DS-3V, 250 X 4.6 mm, 5 jrni or equivalent; wavelength: 220 nm; Temperature: 30°C; Load: 20 \il; Run time: 60 min; and using acetonitrile and water in the ratio of 9:las a diluent and aqueous phosphoric acid as a buffer.
14

The process described in the present invention was demonstrated in examples illustrated below. These examples are provided as illustration only and therefore should not be construed as limitation of the scope of the invention
Examples:
Reference Example: Preparation of ethyl (3R,4S,SR)-4,5-immo-3-(l-ethyIpropoxy)-
1-cyclohexene-l-carboxylate:
Triphenylphosphine (7.9 grams) was added to a mixture of (3R,4S,5R)-ethyl-5-azido-4-hydroxy-3-(pentan-3-yloxy)cyclohex-l-ene carboxylate compound of formula-5 (10 grams) in acetonitrile (25 ml) at 25-30°C. The reaction mixture was heated to reflux temperature and stirred up to the completion of the reaction. The solvent was distilled off under reduced pressure to get the title product as a oily residue. Yield: 7 grams Purity by HPLC: 63.2%
Example-1: Preparation of oxalate salt of ethyl (3R,4$,5R)-4,5-imino-3-(l-ethylpropoxy)-l-cyclohexene-l-carboxylate, compound of formula-3a:
Triphenylphosphine (79 grams) was added to a mixture of (3R,4S,5R)-ethyl-5-azido-4-hydroxy-3-(pentan-3-yloxy)cyclohex-l-ene carboxylate compound of formula-5 (100 grams) in acetonitrile (250 ml) at 25-30°C. The reaction mixture was heated to reflux temperature and stirred up to the completion of the reaction. The solvent was distilled off under reduced pressure, cooled and cyclohexane was added to the residue then distilled off. Ethyl acetate (200 ml) was added to the residue and stirred for 10 minutes at 25-30°C. Oxalic acid (44.5 grams) was added to the reaction mixture, stirred for 30 minutes at 25-30°C. The reaction mixture was cooled to 0-5°C and stirred. The solid was filtered, washed and dried to get the title compound Yield: 85 grams
Purity by HPLC: 98.42 %; 0.52 % (27.7); 0.41% (13.6) MR: 75-80°C; SOR:-40 to-45°(C =1; methanol)
15

ExampIe-2: Preparation of oseltamivir phosphate compound of formula-la:
Zinc dust (77 grams) and aqueous ammonium chloride(77.4 grams in 250 ml of water) was added to a solution of ethyl (3R,4R,5S)-4-acetamido-5-azido-3-(l-ethylpropoxy) cyclohexy-l-ene-1- carboxylate compoimd of formula-4 (100 grams) in isopropyl alcohol (500 ml) at 18-20°C and stirred for an hour. The reaction mixture was quenched with aqueous ammonia and methylene chloride was added to it, stirred and filtered. The aqueous and organic layers from the filtrate separated, extracted the aqueous layer with methylene chloride and washed the organic layer with water. The solvent was distilled off under reduced pressure and the obtained residue treated with phosphoric acid in methanol and stirred. The solid formed was filtered, washed with methanol and dried to get the title compound. Yield: 91 grams Purity by HPLC: 98.40% MR: 198 to 202°C; SOR: -27 to-34° (C =1.5; chloroform)
ExampIe-3: Preparation of oseltamivir compound of formula-1:
Cobaltous chloride (1 gram) was added to a mixture of ethyl (3R,4R,5S)-4-acetamido-5 -azido-3 -(1 -ethylpropoxy)cyclohexy-1 -ene-1 -carboxylate (10 grams), methanol (20 ml), water (100 ml) and methanol (20 ml) at 25-30°C and stirred for 15 minutes. Aqueous sodiumborohydride (1.5 grams in 10 ml of aqueous sodium hydroxide) was added to the reaction mixture and stirred up to completion of the reaction. Methylene chloride (75 ml) was added to the reaction mixture and stirred then filtered through the hyflow. The organic and aqueous layers were separated and extracted aqueous layer with methylene chloride. The aqueous layer was washed with water and drying with sodium sulphite. The solvent from the organic layer co-distilled with acetone under reduced pressure. The obtained residue is purified with column chromatography using hexane and ethyl acetate as an eluent. Yield: 4 grams
16

We Claim:
1. Novel salts of ethyl (3R,4S,5R)-4,5-imino-3-(l-ethylpropoxy)-l-cyclohexene-l-
carboxylate, compounds represented by the following general formula-3,

where in acid is selected from a group, which are capable of forming acid addition salt with ethyl (3R,4S,5R)-4,5-imino-3-(l-ethylpropoxy)-l-cyclohexene-l-carboxylate, and the acid is selected from oxalic acid, succinic acid, fumaric acid, malonic acid, malic acid, maleic acid, tartaric acid, citric acid, methane sulfonic acid, paratoluene sulfonic acid, acetic acid, sulfuric acid, phosphoric acid and hydrohalic acid.
2. Process for the preparation of novel salts of ethyl (3R,4S,5R)-4,5-imino-3-(l-ethyl
propoxy)-l-cyclohexene-l-carboxylate compounds of formula-3,

wherein acid is as defined as above,
which comprises of treating the crude ethyl (3R,4S,5R)-4,5-imino-3-(l-ethyl
propoxy)-l-cyclohexene-l-carboxylate compound of formula-2


with a suitable acid selected from the acids defined above in a suitable solvent selected from alcohols, ketones, esters, hydrocarbons, polar aprotic solvents, polar solvents, chloro solvents, nitriles or mixtures thereof to provide the corresponding acid salt of ethyl (3R,4S,5R)-4,5-imino-3-(l-ethyl propoxy)-l-cyclohexene-l-carboxylate.
3. A process for the preparation of novel salts of ethyl (3R,4S,5R)-4,5-imino-3-(l-ethyl propoxy)-l-cyclohexene-l-carboxylate, compounds of formula-3,

with triphenyl phosphine in a suitable solvent selected from polar aprotic solvent or nitrile solvents, followed by treating with a suitable acid selected from the above defined acids in a suitable solvent selected from alcohols, ketones, esters, hydrocarbons, polaraprotic solvents, polar solvents, chloro solvents, nitriles or mixtures thereof, to provide the corresponding acid addition salt of ethyl (3R,4S,5R)-4,5-imino-3-(l-ethyl propoxy)-l-cyclohexene-l-carboxylate, compounds of formula-3.
18

4. Oxalic acid salt of ethyl (3R,4S,5R)-4,5-imino-3-(l-ethyl propoxy)-l-cyclohexene-l-carboxylate, compound of formula-3a having the following structure.

COOC2H5 Q HO. X
HN" O
Fomiula-3a
5. Crystalline ethyl (3R,4S,5R)-4,5-imino-3-(l-ethylpropoxy)-l-cyclohexene-l-carboxylate oxalate characterized by its DSC which shows two endothermic peaks at 78° C and 141° C.
6. Use of novel salts of ethyl (3R,4S,5R)-4,5-imino-3-(l-ethyl propoxy)-l-cyclohexene-1 -carboxylate,as claimed in claim 1 or oxalate salt as claimed in claim 5 or 6 for the preparation of highly pure ethyl (3R,4S,5R)-4,5-imino-3-(l-ethylpropoxy)-l-cyclohexene-1-carboxylate, compounds of formula-2 or in the preparation of oseltamivir compound of formula-1 and its pharmaceutically acceptable salts.
7. A process for the preparation of oxalate salt of ethyl (3R,4S,5R)-4,5-imino-3-(l-ethyl propoxy)-l-cyclohexene-l-carboxylate, compound of formula-3a having the following structure.

0//,,,,x%/COOC2H5 Q
WW
Formula-3a which comprises of treating the crude ethyl (3R,4S,5R)-4,5-imino-3-(l-ethyl propoxy)-l-cyclohexene-l-carboxylate, compound of formula-2
19


COOCH
2"5

Formula-2 with oxalic acid in a suitable solvent selected from alcohols, ketones, esters, hydrocarbons, polar aprotic solvents, polar solvents, chloro solvents, nitriles or mixtures thereof to provide the oxalic acid sah of ethyl (3R,4S,5R)-4,5-imino-3-(l-ethyl propoxy)-1 -cyclohexene-1 -carboxylate.
8. A process for the preparation of oseltamivir compound of formula-1,


COOC2H5

Formula-1 which comprises of reducing ethyl (3R,4R,5S)-4-acetamido-5-azido-3-(l-ethyl propoxy)cyclohexy-l-ene-l-carboxylate compound of formula-4.


COOC2H5

0^ ^=
Formula-4 in presence of zinc dust and ammonium chloride in a suitable solvent selected from alcohols, ketones, esters, hydrocarbons, polar aprotic solvents, polar solvents, chloro solvents, nitriles or mixtures thereof to provide the oseltamivir compound of formula-1.
20

9. A process for the preparation of oseltamivir compound of formula-1,


COOC2H5

Formula-1 comprises of reducing ethyl (3R,4R,5S)-4-acetamido-5-azido-3-(l-ethyl propoxy)cyclohex-1 -ene-1 -carboxylate, compound of formula-4

COOC2H5
O'
Formula-4 in presence of zinc dust and ammonium chloride in a suitable alcoholic solvents preferably isopropyl alcohol and water, followed by isolating the oseltamivir compound of formula-1 from a suitable chloro solvent preferably methylene chloride.
10. A process for the preparation of oseltamivir compound of formula-1,


COOC2H5

oA
NH2 Formula-1 which comprises of reducing ethyl (3R,4R,5S)-4-acetamido-5-azido-3-(l-ethyl propoxy)cyclohex-l-ene-1-carboxylate compound of formula-4

21


in presence of cobalt ion, a ligand and a reducing agent
wlierein the cobalt ion is selected from the group consisting of cobaltous chloride,
cobaltous diacetate and cobaltic chloride; and the ligand is selected from the group
consisting of dimethylglyoxime, 2,2'-bipyridyl and 1,10-phenathroline; the reducing
agent is selected from the group consisting of sodium borohydride, potassium
borohydride, lithium borohydride, tetra alkyl ammonium borohydride and zinc
borohydride;
and optionally converting the obtained oseltamivir compound of formula-1 into its
pharmaceutically acceptable salt thereof