FORM 2
THE PATENT ACT 1970 (39 of 1970)
& The Patents Rules, 2003 COMPLETE SPECIFICATION
(See section 10 and rule 13)
1. TITLE OF THE INVENTION: "Meropenem intermediate in novel crystalline form1

2. APPLICANT (S)
(a) NAME: Genesen Labs Ltd
(b) NATIONALITY: An Indian Company incorporated under the Indian Companies ACT 1956
(C) ADDRESS:
Genesen Labs Ltd
R-75, TTC industrial area, Thane- Belapur road ,
Rable Navi Mumbai. 400 701.
Tel No. +91-22- 66888700/1
Fax No. +91-22-66888730.
3. PREAMBLE TO THE DESCRIPTION
The following specification particularly describes the invention and the manner in which it is to be performed.

Meropenem intermediate in novel crystalline form
Field of invention:
The present invention relates to novel crystalline form of (4-Nitrobenzyl (4R.5S,6S)-(3-
{(3S>5S)-5-[(dimethylami.no)carbonyl]-l-[(4-nitrophenoxy)carbonxyl] pyrroIidin-3-
yl}thio-6- [(lR)-l-hydorxyethylJ-4-methyl-7-oxo-]-azabicyclo[3.2.0].hept-2-ene-2-
carboxylate) of formula I, also herein after referred as protected meropenem, is a key intermidiate ofmeropenem.

Formula-1 Wherein, PNB represent P-nitro benzyl group and PNZ represent P- nitrobenzyloxycarbonyl group.
Furthermore, present invention relates to an improved and industrially applicable process for production of meropenem trihydrate, chemically designated as trihydrate salt of ((4R,5S,6S)-3-[[(3S!5S)-5-(Dimethylcarbamoyl)-3-pyrrolidinyl]thio]-6-[(lR)-l-hydroxy-ethyl]-4-methyl-7-oxo-l-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid)) of formula-II

Background of Invention:
Meropenem. an ultra-broad spectrum injectable antibiotic used to treat a wide variety of infections, including meningitis and pneumonia, was first disclosed in US4888344. It is a beta-lactam antibiotic and belongs to the subgroup of carbapenem, similar to imipenem and ertapenem.
U.S. Patent No. 4,888,344 provides a process for the preparation of the crystalline
trihydrate of meropenem. U.S. Patent Nos. 4,943,569 and 5,122,604 provide similar
processes for the preparation of meropenem trihydrate. (4-Nitrobenzyl(4R,5S,6S)-(3-
{(3S,5S)-5- [(dimethylamino)carbonyl]-l-[(4-nitrophenoxy)carbonxyl] pyrroIidin-3-
y]}thio-6-[(lR)-l-hydorxyethyl]-4-methyl-7-oxo-]-azabicyclo[3.2.0].hept-2-ene-2-
carboxylate) known as key intermediate of meropenem (formula-I) chemically known
((4R,5S,6S)-3-[[(3S,5S)-5-(Dimethylcarbamoyl)-3-pyrrolidinyl]thio]-6-[(lR)-l- hydroxy-
ethyl]-4-methyl-7-oxo-l-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid)),formula-II
which is synthetic broad spectrum,carbapenem antibiotic.
The compound of formula-I in non crystalline form e.g amorphous form, in form of oil, foamy solid generally is known with poor materials properties such as stability or purity and isolating properties compared to crystalline forms. In synthesis, the obtainment of product in crystalline form is necessary as the same is available with more purity. Moreover, the crystalline materials have substantially better stability than amorphous form.
WO2006/035300 A2 describes a process for preparing Meropenem by using biphasic solvent system for the deprotection of compound of formula (V), which is similar to the teachings provided in US 4.943.569. where ethyl acetate was added after the hydrogenation to remove organic impurity.
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Formula-V
WO2006/035300A2 further claims a process for preparing Meropenem trihydrate in which the penultimate compound of formula (V) was not isolated. This teaching is similar to the disclosure of US 4,888.344. where, the suggestion has given to the extent that Meropen trihydrate can be directly crystallized out from the resultant aqueous concentrate.
WO2005/118586 Al claims crystalline penultimate compound of formula-I and a process for preparing this intermediate. According to this publication, the intermediate is crystallized out either from concentrating the mother liquor in alky] alkanoate such as ethyl acetate or by the addition of anti-solvent such as cyclohexane or heptane to the mother liquor in ethyl acetate. Since this publication describes the use of multiple solvent systems, the processes are not commercially viable from industrial point of view owing to multiple solvent recoveries, thus, adding further cost to the production.
As per US 4,888,344 in example 1. Meropenem is dissolved in water, where upon small amount of meropenem crystals formed and further addition of acetone yielded meropenem trihydrate. Since the sterile preparation requires complete dissolution for sterile filtration, this technique is not found attractive.
According to the above mentioned patent literature. Meropenem trihydrate was obtained by subjecting the aqueous reaction mass after the deprotection of protecting group to
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hydrogenation at high pressure, and also to reverse osmosis (if necessary), followed by adding water-miscible organic solvent such as ethanol, iso-propanol, acetone, tetrahydroftiran (THF). dioxane, acetonitrile, etc.
In our embodiment ,such type of explosive step like hydrogenation at high pressure has been avoided to obtain meropenem trihydrate.
Therefore, there is need to provide a cost effective and eco-friendly process for preparation of meropenem trihydrate. Accordingly the present invention provides a process which devoid of the use of expensive and hazardous reagents and critical reaction parameters. Also, the solvent used as reaction medium is recovered to grater extant after the completion of reaction, which makes the process commercially applicable for industrial scale furthermore, the embodiment is deprotection reaction carried out at 6.5 to 6.9 pH of reaction mass by using the carbonate water or phosphate buffer or morpholine buffer of pH-7 so as to achieve maximum yield and good purity.
Object of invention:
The main object of the present invention is to provide the novel crystalline form of protected meropenem.Another objective of the present invention is to provide commercially applicable process with suitable reaction parameters as well as less no of operations for preparation of meropenem trihydrate. Other fetches of the invention is to provide cost effectiveness and environment friendly process over the existing prior art.
Summary of invention:
The present invention mainly directed to the novel crystalline form of protected meropenem which has a good stability over amorphous form and furthermore to provide a cost effective and eco friendly process for preparation of meropenem trihydrate.
In preferred aspect, compound of formula A, (4-nitrobenzyl(4R,5R,6S)-3-[(diphenoxyphosphoryl)oxy]-6-[(lR)-l-hydroxyethyl]-4-methyl-7-oxo-l-
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azabicyclo[3.2.0]hept-2-ene-2-carboxylate) and compound B, (4-nitrobenzyl(2S',4S)-2-[(dimethylamino)carbonyl]-4-mercaptopyrrolidine-l-carboxylate) are condensed in a mixture of acetonitrile and dimethyl acetamide at -5 to -10 °C; followed by addition of di-isopropylethylamine in dropwise manner at same temperature. After completion of the reaction, the reaction mass is extracted with ethyl acetate and distilled out completely with concomitant stoichiometric addition of methyl ethyl ketone and acetone with continued stirring at 0-5 °C, followed by addition of water and small amounts of seeding to get novel crystalline form of protected meropenem.
The process for the same is depicted in scheme I as follows:

In another aspect, the deprotection of protected meropenem by hydrogenation at atmospheric pressure in mixture of tetrahydrofuron and water as solvent media with palladium on charcoal at room temperature at pH of reaction mass 6.5 to 7.5 to get meropenem trihydrate in desirable yield and purity .


The process for the same is depicted as follows;
Wherein,
PNB represent P-nitro benzyl group and PNZ represent P- nitrobenzyloxycarbonyl group.
Thus according to the present invention, the compound of formula-I is obtained in novel crystalline form which has been found under the exemplified conditions. The novel crystalline form (Figure-I) of meropenem intermediate,which has above mentioned advantages and can be used in preparation of meropenem .
The certain crystalline form found under the certain condition which has been elaborately described in forgoing examples. The physiochemical properties of the compound formula ~I in novel crystalline form may be describe as follows.
a) External appearance :
Light yellow, needle type crystals.
b) Melting point
151-153 °C
c) X-ray powder diffractogram
The compound of formula -I in crystalline form (Figure -I) shows characteristic bands at the 2-theta diffraction angles at about 5.01, 7.0, 10.3, 15.5, 17.0,20.8,22.6 and 26.4.
X- ray powder difractogram of compound formula I in crystalline form recorded on AXS-Bruker-D-8 advance, equipped with Brag-Brentano 9- 8 gonion meter
using tube voltage of 40 Kv and tube current 40 mA with step size 0.013° ,time of steps of 1 second over an angular range of 3 - 45 ° ,2 theta. The sample was exposed to the Cu K alpha radiations (lambda = 1.5418 A0) evaluation was carried out using software EVA.
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Powder diffractogram of (4-Nitrobenzyl(4R.5S,6S)-(3-{(3S.5S)-5-
[(dimethyIamino)carbonyl]-l-[(4-nitrophenoxy)carbonxy|]pyrroIidin-3-yI!thio-6-[(lR)-l-
hydorxyethylJ-4-methyl-7-oxo-l-azabicyclo|3.2.0].liept-2-ene-2-carboxylate), are
provided below in table 1.
Table 1

Caption Angle d value Intensity Intensity %
2-Theta ° Angstrom Count
A-5.099 ° 5.099 17.31-756 1946 100
A=7.028 ° 7.028 12.56692 205 10.5
A-IO.3360 10.336 8.55159 722 37.1
A=12.515° 12.515 7.0674 143 7.4
A=12.824° 12.824 6.89778 196 10.1
A=13.120° 13.12 6.74238 233 12
A=13.460° 13.46 6.57325 266 13.7
A=I3.935° 13.935 6.35002 287 14.7
A=14.148° 14.148 6.25482 313 16.1
A=15.472° 15.472 5.72235 832 42.7
A-15.751 ° 15.751 5.62166 463 23.8
A=l 6.987° 16.987 5.21529 1407 72.3
A=17.561 ° 17.561 5.0462 615 31.6
A=18.335° 18.335 4.83496 482 24.8
A=19.085° 19.085 4.64653 230 11.8
A=19.719° 19.719 4.49848 519 26.7
A=20.101 ° 20.101 4.41393 445 22.8
A=20.769 ° 20.769 4.27349 777 39.9
A=22.112° 22.112 4.0168 226 11.6
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A=22.541 ° 22.541 3.94135 595 30.6
A=23.300 ° 23.3 3.81463 622 32
A-24.031 ° 24.031 3.70026 458 23.5
A-24.885 ° 24.885 3.5751 188 9.7
A=25.345 ° 25.345 3.51129 282 14.5
A=26.421 ° 26.421 3.37066 363 18.7
A-27.525 ° 27.525 3.23795 236 12.1
A-28.925 ° 28.925 3.08437 217 11.1
A=31.233° 31.233 2.8615 130 6.7
The compound of formula I may be obtained by condensing (4-nitrobenzyl (4R,5R,6S)-3-
[(diphenoxyphosphoryl)oxy]-6-[(lR)-l-hydroxyethyl]-4-methyI-7-oxo-l-
azabicyclo[3.2.0]hept-2-ene-2-carboxylate) and (4-nitrobenzyl(2S',4S)-2-
[(dimethylamino)carbonyl]-4- mercaptopyrrolidine-1-carboxylate) in acetonitrile and dimethyl acetamide as solvent media furthermore added diisopropyl ethylamine . After completion of reaction, distilled out the complete solvent media and added combination of ketone based solvents for crystallization, and finally, added polar protic solvent to complete crystallization.
The ketone based solvents are ethyl methyl ketone, methyl butyl ketone, acetone, isobutyl ketone, diethyl ketone etc. or mixture thereof, but preferably acetone and methyl ethyl ketone are used to obtain crystalline form of compound of formula-1..
Polar protic solvents are selected from water, methanol, dimethyl acetate, but preferably water is used to get complete crystallization. The compound formula-1, is crystallized and isolated in usual manner having excellent stability and having typical purity more than 99.0 % by HPLC area percentages.
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Another aspect of the present invention is to provide industrially applicable process for preparation of meropenem of formula II from crystalline compound formula -I by hydrogenation at atmospheric pressure, whereby protected meropenem i.e. compound of formula-I is deprotected by using palladium on carbon in solvent mixture of tetrahydrofuran and carbonate water or phosphate buffer or morpholine buffer of pH-7 at temperature 30-35 °C and the pH of reaction mass should be 6.5 to 6.9 so as to exerts desired yield and purity which has been exemplified in the foregoing description as well as in examples.
Detail description of Invention:
While the invention will now be described in detail in connection with certain preferred and optional embodiments, so that various aspects thereof may be more fully understood and appreciated, it is not intended to limit the invention to these particular embodiments.
The method described herein below provides substantial benefits relative to previously used or suggested production methods. For example, the starting materials, intermediates, liquid media, and catalysts used are relatively easier to handle and to dispose off, if necessary. Importantly, the present method provides high yields of the desired product or products so that substantial process efficiencies are achieved.
Preparation of novel crystalline polymorph of protected meropenem preperation is depicted as follows:
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In preferred embodiment, formula A is condensed with formula B in solvent media acetonitrile in presence of polar protic solvent dimethyl acetamide and added diisopropyl ethylamine as reaction accelerator at a temperature ranging from -10 to -5 °C up to completion of reaction. The reaction is monitored by HPLC (High performance liquid chromatography) followed by extraction with ethyl acetate. Furthermore, complete distillation of ethyl acetate added stoichiometric proportion of methyl ethyl ketone and acetone to the said reaction mass and continued with stirring at 0-5 °C for 14 hrs . Finally added cold water and small amount of seeding and allow to stirr at same temperature for complete crystallization.
Thus, according to preferred embodiment, molar ratio of formula A and formula B is in stoichiometric proportion. Acetonitrile as solvent media is used 2-4 times, preferably, 4 times w.r.t formula A and polar protic solvents are DMSO, dimethyl acetamide, dimethyl formamide etc. but preferably dimethyl acetamide used in at least 1- 2 times w.r.t to formula A, followed by addition of diisopropyl ethylamine in proportion of 2-4 times w.r.t formula B, preferably 2 times in such a way that to maintain reaction temperature to
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accelerate fastly. Finally, after completion of the reaction, the reaction mass is extracted by ethyl acetate and distilled out completely followed by addition of methyl ethyl ketone and acetone to set crystallization point in stoichiometric proportion, preferably 1: 1.25 and for complete crystallization polar miscible solvent like water is added at least in one proportion with respect to mixture of ethyl methyl ketone and acetone.
The process described as above is used to manufacture of proteceted meropenem in crystalline form with desirable yield in about 90-95 % and with purity above 99%. Furthermore, protected meropenem is treated with palladium on charcoal (Pd/C) in mixture of tetrahydrofuran and carbonate water or phosphate buffer or morpholine buffer of pH-7 so as to retain reaction mass pH 6.5 to 6.9 at temperature of 30-35 °C for 2- 3 hrs. to get maximum yield. After completion of reaction, degasified and charcoalised the reaction mass to get clear aqueous layer which is further reduced by distillation and finally acetone is added at maintained temperature of 0-5 °C for 3 hrs to get crystalline meropenem trihydrate in pure form.
Thus, in another embodiment, the invention provides isolation of meropenem trihydrate from reaction mass which comprises the following steps:
a) After completion of reaction, adjusting the pH of reaction mass in range 6-7 by using sodium carbonate solution if necessary;
b) Degasifying the reaction mass followed by charcoalizing and filtering at ambient temperature;
c) Reducing the aqueous layer under vacuum below 35 °C;
d) Adding acetone to above aqueous layer at temperature of 0-5 °C and continuing the stirring for 3 hrs for complete precipitation;
e) Filtering and washing the cake by acetone to get pure meropenem trihydrate.
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Wherein,
PNB represent P-nitro benzyl group and PNZ represent P- nitrobenzyloxycarbonyl group.
The deprotection step as depicted above, is carried out at 30-35 °C in monophasic solvent system with mole ratio of protected meropenem and palladium on charcoal as 1:0.25. The pH of reaction mass plays vital role in acceleration of reaction to achieve good yield. The pH of reaction mass should be in range 6-7 so as to get maximum yield and the side product p-nitro toluene will be in non aq. layer and maximum meropenem will goes into aq. layer by maintaining water of pH 7. so as to achieve maximum yield. The process of present invention to manufacture meropenem trihydrate has been well depicted in forgoing Examples.
Following examples are offered to provide the general state of preparation for meropenem trihydrate the person skill in the art with sufficiently clear and complete explanation of this invention, but should not consider as a limitation to the essential aspect of the object thereof, as they have been explained in below.
Example-1
Preparation of protected meropenem.
4-nitrobenzyl (4R,5R,6S)-3-[(diphenoxyphosphoryl)oxy]-6-[(lR)-l -hydroxyethyl]-4-methyl-7-oxo-l-azabicyclo[3.2.0]hept-2-ene-2-carboxylate (10 gm) formula -A and 4-nitrobenzyl (2S,4S)-2-[(dimethyIamino)carbonyi]-4- mercaptopyrrolidine-1 -carboxylate (6.122 gm) formula-B was dissolved in 60 ml acetonitrile and 3 ml dimethyl acetamide at ambient temperature .The solution was stirred under same condition for 10 minutes to get clear solution and cool to -10 °C. Di-isopropylethyl amine (9.15ml) was added
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dropwise under stirring condition to the above solution at -10 °C and continued the reaction for 90 minutes at same reaction parameters. After completion of reaction, added 150 ml ethyl acetate in said reaction mass, extracted the ethyl acetate layer by acidic water till to get pH 6-7 of extracted acidic water .Dried over sodium sulphate and distilled off up to free solid. Added 1:1 mixture of 50 ml methyl ethyl ketone and acetone and allowed to keep for 14 hrs for crystallization at 0-5 °C , finally added 30 ml cold water with small amount of seeding for complete crystallization filter the solid and washed with 10 ml mixture of diethyl ether and ethyl acetate to obtain pure 4-Nitrobenzyl (4R.5S.6S)-3-({(3S.5S)-5- [(dimethylamino)carbonyl]-l-[(4-nitrophenoxy)carbonxyl]pyrrolidin-3-yl}thio)-6-[(]R)-l-hydorxyethy]J-4-methyl-7-oxo-l-azabicyclo[3.2.0].hept-2-ene-2-carboxylate (referred as protected meropenem ) Yield = 10.20 gm . purity = 99 % above.
ExampIe-II
Preparation of Meropenem trihydrate .
Charged 4-Nitrobenzy](4R.5S.6S)-3-({(3S,5S)-5-[(dimethylamino)carbonyl]-l-[(4-
nitrophenoxy) carbonxyl]pyrrolidin-3-yl}thio)-6-J"(lR)-l-hydorxyetliyll-4-methyl-7-oxo-l-azabicyclo[3.2.0].hept-2-ene-2-carboxylate (refened as protected meropenem ) obtained from example-I in 50 ml of tetra hydrofuran and 2,5 gms 10% palladium on activated charcoal and added 50 ml of aqueous solution of sodium hi carbonate or phosphate buffer or morpholine buffer to maintain the pH at about 6.5 - 6.9 The above reaction mixture was hydrogenated at atmospheric pressure for 3 hours at 30-35 °C. After completion of reaction, the mixture was filtered and degasifies completely. The aqueous layer was charcoalised for 30 minutes to get clear transparent layer, followed by washing the aqueous layer with 20 ml ethyl acetate. The aqueous layer is concentrated under vacuum below 35 °C and 400 ml acetone was added to aqueous layer slowly at temperature about 0-5 °C , resultant mass was stirred for 3 hours at same temperature .The separated solid was filtered, washed with chilled acetone and dried at ambient temperature to get meropenem trihydrate. Yield-5.10 gm.
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Example-Ill
Preparation of sterile Meropenem trihydrate
Charged 4-Nitroben2yl(4R.5S.6S)-3-(U3S,5S)-5-[(dimethyiamino)carbonyl]-l-[(4-
nitrophenoxy) carbonxy!]pyrrolidin-3-yl}thio)-6-[(lR)-l-hydorxyethyl]-4-methy]-7-oxo-l-azabi"cycfo[3.2.0J.hept-2-ene-2-carboxyfate (refen-ed as protected meropenem ) obtained from example-I in 50 ml of tetra hydrofuran and 2.5 gms of 10 % palladium on activated charcoal and added 50 ml of aqueous solution of sodium bi carbonate or phosphate buffer or marpholine buffer of pH-7 to maintained pH 6.5 - 6.9 The above reaction mixture was hydrogenated at atmospheric pressure for 2 hours at 30-35 °C. After completion of reaction, the mixture was filtered and degasifies completely. The aqueous layer was charcoalised for 30 minutes to get clear transparent layer, which was washed with 20 ml ethyl acetate. The combined aqueous layers were filtered through series of 0.45 and 0.22 u under aseptic condition and the filtrate was concentrated under vacuum below 35 °C. 400 ml acetone previously filter through 0.22 u was added to aqueous layer under aseptic condition slowly at controlled temperature about 0-5 °C and resultant mass was stirred for 3 hours at same temperature .The separated solid was filtered, washed with chilled acetone and dried at ambient temperature to get meropenem trihydrate
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We Claim:
1. A novel crystalline form of compound of formula-I referred as protected meropenem(formula-I) is characterized by XRD, having 2 theta diffraction angle at about 5.01, 7.0, 10.3, 15.5, 17.0, 20.8, 22.6 and 26.4.


OPNB PNZ
Formula-1 Wherein, PNB represent P-nitro benzyl group and PNZ represent P- nitrobenzyloxycarbonyl group.

2) The novel crystalline form of compound of formula-I as in claim 1, wherein, X-ray diffraction pattern is as follows:

Caption Angle d value Intensity Intensity %
2-Theta ° Angstrom Count
A=5.099 ° 5.099 17.31756 1946 100
A-7.028 ° 7.028 12.56692 205 10.5
A=10.336° 10.336 8.55159 722 37.1
A=12.515° 12.515 7.0674 143 7.4
A=12.824° 12.824 6.89778 196 10.1
A=13.120° 13.12 6.74238 233 12
A=13A60° 13.46 6.57325 266 13.7
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A=13.935° 13.935 6.35002 287 14.7
A=14.148° 14.148 6.25482 313 16.1
A=15.472° 15.472 5.72235 832 42.7
A=15.751 ° 15.751 5.62166 463 23.8
A-16.987° 16.987 5.21529 1407 72.3
A=17.561 ° 17.561 5.0462 615 31.6
A=18.335° 18.335 4.83496 482 24.8
A-19.085 ° 19.085 4.64653 230 11.8
A=19.719° 19.719 4.49848 519 26.7
A=20.101 ° 20.101 4.41393 445 22.8
A=20.769 ° 20.769 4.27349 777 39.9
A-22.112° 22.112 4.0168 226 11.6
A-22.541 ° 22.541 3.94135 595 30.6
A=23.300 ° 23.3 3.81463 622 32
A-24.031 ° 24.031 3.70026 458 23.5
A-24.885 ° 24.885 3.5751 188 9.7
A=25.345 ° 25.345 3.51329 282 3 4.5
A-26.421 ° 26.421 3.37066 363 18.7
A=27.525 ° 27.525 3.23795 236 12.1
A-28.925 ° 28.925 3.08437 217 11.1
A=31.233° 31.233 2.8615 130 6.7
3) A process for preparation of compound of formula I comprising the following steps:
a) Dissolving non crystalline or foamy solid of compound of formula 1 in effective
combination of ketonic solvents selected from the group consisting of ethyl methyl
ketone, acetone, methyl butyl ketone, acetone, diethyl ketone or mixture thereof;
b) Crystallizing the reaction mass at 0-5 °C and
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c) Adding polar protic solvent selected from the group consisting of water, methanol, DMSO to affect complete crystallization to obtain crystalline form of compound formula I.
4) The process for preparation of compound of formula I as claim in claim 3 (a) wherein, said effective combination of ketone solvent is ethyl methyl ketone and acetone in stoichiometric proportion.
5) The process for preparation of compound of formula I as in claim 3 (b), wherein, said polar protic solvent used for complete crystallization is water.
6) A process for preparation of meropenem of compound of formula II comprising following steps:

a) Deprotecting the protected meropenem by hydrogenation at atmospheric pressure at temperature 30-35 °C in water miscible solvent system like acetone, water, methanol, tetrahydrofuran, ethanol or mixture thereof, at pH 6.5 to 6.9 so as to achieve maximum yield;
b) In deprotection reaction pH of reaction mass is in 6.5 to 6.9 maintain by using coarbonate ware or phosphate buffer or morpholine buffer of pH-7
c) Degasifying and charcoalizing the reaction mass to obtain clear aqueous layer
followed by adding acetone at 0-5 °C to obtain meropenem trihydrate.
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7) The process for preparation of meropenem as in claim 6 (a & b) wherein, said miscible solvent system is carbonate water or phosphate buffer or morpholine buffer of pH-7 and tetrahydrofuran.
8) The process for preparation of compound of formula I as claimed in claim 6 (c) wherein, said deprotection is carried out preferably at 30-32°C to achieve maximum yield.
9) The process for preparation of meropenem as in claim 6 (b) wherein, said deprotection is carried out preferably at pH 6.5-6.9 by hydrogenating at atmospheric pressure so as to achieve maximum yield.


Applicant Mr. Ashwin A. Khemka

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