The present invention provides a process for the recovery of homogeneous catalyst from a catalytic reaction mixture.
Homogeneous catalysis is involved in the preparation of several commercially useful intermediates and pharmaceutical compounds including carbapenem antibiotics. These catalytic reactions generally use salts and/or complexes of a Group VIII metal, such as rhodium, platinum, palladium or cobalt, as the homogeneous catalyst.
A catalyst is a substance which is not generally consumed in the reaction. Since the catalyst is not consumed, it is economically desirable to recover the catalyst for further use. Such recovery and recycling of catalysts are more important while expensive metals such as rhodium are used in the catalysis. The recovery of catalysts is also important in the pharmaceutical industry, because the final product should not be contaminated with the metals involved in catalysis.
The recovery of the homogeneous catalysts is usually carried out by methods such as adsorption on activated carbon, silica gel, alumina and resins. However, these methods pose certain problems in that the metal is present in very low concentrations, usually measured in parts per million, and that the adsorbent is difficult to getrid of the metal. EP Patent Application No 0,182,409 A2 provides a process for the recovery of rhodium catalysts by adsorption on resin bearing a non-ionic heterocyclic electron donor. This process further involves the use of mixture of solvents for catalyst recovery. US Patent No 4,413,118 provides a process for removing homogeneous catalyst group VIII metals from chemical process streams which comprises treating the process streams with organic sulfur compounds containing a carbon-sulfur double bond such as thiourea. US Patent No 4,050,629 provides a process for recovery of rhodium(ll)octanoate from a catalylic reaction mixture by removing the reaction solvent, adding formic acid (98%), and recovering the precipitated homogeneous catalyst by filtration.
US Patent No 5,493,018 provides a process for the preparation of carbapenem intermediate of Formula I,
(Formula Removed)
FORMULA I
using rhodium(ll)octanoate and Lewis acid catalysts. However, the '018 patent does not provide or suggest any method for recovering rhodium(ll)octanoate from the reaction mixture.
The processes provided in the prior art for homogeneous catalyst recovery involve the use of resins or treatment of process streams sulfur compound, which makes the process costlier and not preferable in industrial scale. The processes also involve the filtration of catalytic reaction mixture containing excess of formic acid, which is not safe in large scale. The present inventors have also observed that the quality of the recovered homogeneous catalysts using the prior art processes is also poor and they often need to be re-activated.
While working on this problem, the present inventors have developed a novel process for the recovery and recycling of homogeneous catalyst. The present invention provides the recovery of homogeneous catalyst by simple layer separation and isolation. The present process does not require the use of any adsorbents, expensive resins or sulfur compounds, and thus improves the process economy. The present process can be carried out from a single solvent and it avoids the filtration of catalytic reaction mixture containing formic acid. Further, the present inventors have surprisingly found that the homogeneous catalysts recovered according to the present method are in active form up to about 80% or above, and can be recycled more than about 10 times. Thus, the present invention provides a simple, economic and industrially preferable process for recovery and recycling of homogeneous catalysts. The present
invention also provides a process for the preparation of carbapenem antibiotics by employing the present methods of catalyst recovery.
The term "protecting group" in the present invention refers to those used in the art and serve the function of blocking the carboxyl, amino or hydroxyl groups while the reactions are carried out at other sites of the molecule. Examples of a carboxyl protecting group include, but not limited to, optionally substituted C1-C8 alkyl, optionally substituted C3-C8 alkenyl, optionally substituted C7-C19 aralkyl, optionally substituted C6-C12 aryl, optionally substituted C1-C12 amino, optionally substituted C3-C12 hydrocarbonated silyl, optionally substituted C3-C12 hydrocarbonated stannyl, and a pharmaceutically active ester forming group. Examples of hydroxyl and amino protecting groups include, but not limited to, lower alkylsilyl groups, lower alkoxymethyl groups, aralkyl groups, acyl groups, lower alkoxycarbonyl groups, alkenyloxycarbonyl groups and aralkyloxycarbonyl groups.
A first aspect of the present invention provides a process for recovering the homogeneous catalyst, wherein the said process comprises,
a) treating a reaction mixture comprising homogeneous catalyst and a water
immiscible organic solvent, with a C1-2 alkanoic acid, and
b) recovering the homogeneous catalyst from the reaction mixture obtained in
step a) by layer separation.
The reaction mixture involved in step a) can be a catalytic reaction mixture, which results after the completion of any homogeneous catalytic reaction. The reaction mixture involved in step a) is preferably obtained after isolating the reaction products from the reaction medium. The reaction mixture involved in step a) comprises the homogeneous catalyst and a water immiscible organic solvent. The homogeneous catalysts are metal containing compounds or complexes in which the metal is a Group VIII metal. The Group VIII metal is preferably selected from platinum group, and more preferably the Group VIII metal is rhodium. The metal containing compounds or complexes are selected from a group comprising
of the metal C2-C10 carboxylates and metal complexes with ligands such as CO; R'3Z, (R'O)3Z and (R'O)2ZR, wherein R' is alkyl, aryl, aralkyl or alkaryl group, and Z is P, Sb or As. The metal containing compound is preferably selected from rhodium carboxylates and more preferably the rhodium containing compound is rhodium(ll)octanoate. The water immiscible organic solvent used in step a) can be a single or mixture of reaction solvents employed for homogeneous catalytic reaction. The water immiscible organic solvent also comprises the solvents which can be added to the reaction mixture before the recovery of the homogeneous catalysts, but after the completion of catalytic reaction. The water immiscible organic solvent is selected from a group comprising of toluene, methylene chloride, methyl t-butyl ether, xylene, 1,2-dichloroethane and cyclohexane.
The reaction mixture comprising homogeneous catalyst and a water immiscible organic solvent is treated with a C1-2 alkanoic acid. The C1-2 alkanoic acid can be formic acid or acetic acid. The C1-2 alkanoic acid is preferably used in the form of aqueous solution. The organic layer containing the homogeneous catalyst is subsequently separated from the reaction mixture and it can be directly used in further homogeneous catalytic reactions. The homogeneous catalyst can also be isolated from the organic layer by any conventional separation techniques such as concentration or distillation.
A second aspect of the present invention provides a process for the preparation of the compound of Formula I,
(Formula Removed)
FORMULA I
wherein P1 is hydrogen or a carboxyl protecting group, P3 is hydrogen or a hydroxyl protecting group, and R1 is hydrogen or C1-3 alkyl group, or its stereoisomers, or salts thereof,
wherein the said process comprises,
a) treating the compound of Formula II with a homogeneous rhodium catalyst in a
water immiscible organic solvent,
(Formula Removed)
FORMULA II
wherein P1 is hydrogen or a carboxyl protecting group, P2 is hydrogen or an
amino protecting group, P3 is hydrogen or a hydroxyl protecting group, and RI is
hydrogen or C1-3 alkyl group, to obtain the compound of Formula I,
b) isolating the compound of Formula I or its stereoisomers, or salts thereof, from
the reaction mixture thereof,
wherein step b) further comprises recovering the homogeneous rhodium catalyst
from the reaction mixture by layer separation.
The compound of Formula II can be prepared as per the methods provided in WO 05/021560, JP 3479720 B2, or WO 03/080571. The compound of Formula II is treated with a homogeneous rhodium catalyst in the presence of a water immiscible organic solvent to obtain the compound of Formula I. The homogeneous rhodium catalyst is selected from rhodium carboxylates and the homogeneous rhodium catalyst is preferably rhodium(ll)octanoate. The water immiscible organic solvent is selected from a group comprising of toluene, methylene chloride, methyl t-butyl ether, xylene, 1,2-dichloroethane and cyclohexane.
The compound of Formula I or its stereoisomers, or salts thereof is subsequently isolated from the reaction mixture by solvent precipitation and filtration. The resultant reaction mixture comprising homogeneous catalyst and a water immiscible organic solvent is treated with a C1-2 alkanoic acid. The C1-2 alkanoic can be formic acid or acetic acid. The C1-2 alkanoic acid is preferably used in the
form of aqueous solution. The organic layer containing the homogeneous catalyst is subsequently separated from the reaction mixture. This organic layer can be directly used in further homogeneous catalytic reactions. The homogeneous catalyst can also be optionally isolated from the organic layer by any conventional separation techniques such as concentration or distillation.
A third aspect of the present invention provides a process for the preparation of the compound of Form III,
(Formula Removed)
FORMULA III
wherein P1 is hydrogen or a carboxyl protecting group, P3 is hydrogen or a
hydroxyl protecting group, R1 is hydrogen or C1-3 alkyl group, and B is
OP(O)(OR)2 or OSO2R, wherein R is substituted or unsubstituted C1-6 alkyl,
aralkyl or aryl, or its stereoisomers, or salts thereof,
wherein the said process comprises,
a) treating the compound of Formula II with a homogeneous rhodium catalyst in a
water immiscible organic solvent,
(Formula Removed)
FORMULA II

wherein P1 is hydrogen or a carboxyl protecting group, P2 is hydrogen or an amino protecting group, P3 is hydrogen or a hydroxyl protecting group, and R1 is hydrogen or C1-3 alkyl group, to obtain the compound of Formula I,
(Formula Removed)
FORMULA I
wherein P1 P3 and R1 are as defined above,
b) reacting the compound of Formula I with a compound of Formula X-Bi,
wherein B1 is -P(0)(OR)2 or -SO2R, wherein R is substituted or unsubstituted C1-6
alkyl, aralkyl or aryl, and X is halogen, to obtain a compound of Formula III,
c) isolating the compound of Formula III or its stereoisomers, or salts thereof,
from the reaction mixture thereof,
wherein step c) further comprises recovering the homogeneous rhodium catalyst from the reaction mixture by layer separation.
The compound of Formula II can be prepared as per the methods provided in WO 05/021560, JP 3479720 B2, or WO 03/080571. The compound of Formula II is treated with a homogeneous rhodium catalyst in the presence of a water immiscible organic solvent to obtain the compound of Formula I. The homogeneous rhodium catalyst is selected from rhodium carboxylates and the homogeneous rhodium catalyst is preferably rhodium(ll)octanoate. The water immiscible organic solvent is selected from a group comprising of toluene, methylene chloride, methyl t-butyl ether, xylene, 1,2-dichloroethane and cyclohexane.
The compound of Formula I is subsequently reacted with a compound of Formula X-B1 to obtain enolphosphate of Formula III. This reaction is carried out in the presence of a base. The enolphosphate of Formula III is isolated from the reaction mixture by solvent precipitation and filtration. The resultant reaction mixture comprising homogeneous catalyst and a water immiscible organic solvent is treated with a C1-2 alkanoic acid. The C1-2 alkanoic acid can be formic acid or acetic acid. The lower alkanoic acid is preferably used in the form of
aqueous solution. The organic layer containing the homogeneous catalyst is subsequently separated from the reaction mixture. This organic layer can be directly used in further homogeneous catalytic reactions. The homogeneous catalyst can also be optionally isolated from the organic layer by any conventional separation techniques such as concentration or distillation.
A fourth aspect of the present invention provides a process for the preparation of carbapenem compounds of Formula IV,
(Formula Removed)
FORMULA IV
wherein PI is hydrogen or a carboxyl protecting group, P3 is hydrogen or a hydroxyl protecting group, R1 is hydrogen or C1-3 alkyl group, and A is selected from a group comprising of
(Formula Removed)
wherein P2 is hydrogen or an amino protecting group, R2 and R3 are same or different and are hydrogen, C1-5 alkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl, or its stereoisomers, or salts thereof, wherein the said process comprises,
a) treating the compound of Formula II with a homogeneous rhodium catalyst in a water immiscible organic solvent,
wherein Pi, P2, P3 and R1 Formula I,
(FormulaRemoved)
FORMULA II
are as defined above, to obtain the compound of

(Formula Removed)
FORMULA I
wherein P1, P3 and R1 are as defined above,
b) reacting the compound of Formula I with a compound of X-B1, wherein B1 is -
P(0)(OR)2 or -SO2R, wherein R is substituted or unsubstituted C1-6alkyl, aralkyl
or aryl, and X is halogen, wherein R is substituted or unsubstituted C1-6 alkyl, aralkyl or aryl, and X is halogen, to obtain a compound of Formula III,
(Formula Removed)
FORMULA III
wherein P1 P3, R1 and B are as defined above,
c) reacting the compound of Formula III with a compound of Formula V,
(Formula Removed)
FORMULA V
wherein A is as defined above, to obtain the compound of Formula IV
d) isolating the compound of Formula IV or its stereoisomers, or salts thereof,
from the reaction mixture thereof,
wherein the homogeneous rhodium catalyst is recovered from the reaction mixture of step a) or step b) by layer separation.
The compound of Formula II can be prepared as per the methods provided in WO 05/021560, JP 3479720 B2, or WO 03/080571. The compound of Formula II is treated with a homogeneous rhodium catalyst in the presence of a water immiscible organic solvent to obtain the compound of Formula I. The homogeneous rhodium catalyst is selected from rhodium carboxylates and the homogeneous rhodium catalyst is preferably rhodium(ll)octanoate. The water immiscible organic solvent is selected from a group comprising of toluene, methylene chloride, methyl t-butyl ether, xylene, 1,2-dichloroethane and cyclohexane.
The compound of Formula I is subsequently reacted with a compound of Formula X-Bi to obtain enolphosphate of Formula III. This reaction is carried out in the presence of a base. The enolphosphate of Formula III is isolated from the
reaction mixture by solvent precipitation and filtration. The resultant reaction mixture comprising homogeneous catalyst and a water immiscible organic solvent is treated with a C1-2 alkanoic acid. The C1-2 alkanoic acid can be formic acid or acetic acid. The C1-2 alkanoic acid is preferably used in the form of aqueous solution. The organic layer containing the homogeneous catalyst is subsequently separated from the reaction mixture. This organic layer can be directly used in further homogeneous catalytic reactions. The homogeneous catalyst can also be optionally isolated from the organic layer by any conventional separation techniques such as concentration or distillation.
The isolated enolphosphate of Formula III reacted with a thiol side chain of Formula V in the presence of a secondary or tertiary amine. The resultant compound of Formula IV or its stereoisomers, or salts thereof, is subsequently isolated from the reaction mixture. The compound of Formula IV is optionally deprotected using palladium catalyst. The deprotection step can be carried out without isolating or after isolating the compound of Formula IV.
While the present invention has been described in terms of its specific embodiments, certain modifications and equivalents will be apparent to those skilled in the art and are intended to be included within the scope of the present invention.
EXAMPLE 1
PREPARATION OF 4-NITROBENZYL (5R,6S)-6-[(1R)-1-HYDROXYETHYL]-
3.7-DIOXO-1-AZABICYCLO[3.2.0]HEPTANE-2-CARBOXYLATEAND
RECOVERY OF RHODIUM(II)OCTANOATE
Step (a): Preparation of 4-nitrobenzyl (5R,6S)-6-[(1R)-1-hydroxyethyl]-3,7-dioxo-1-azabicyclo[3.2.0]heptane-2-carboxylate:
(3S,4R)-3-[(1R)-Hydroxyethyl]-4-[3-(4-nitrobenzyloxy)carbonyl-2-oxo-3-diazopropyl]azetidin-2-one (100 g; 265.9 mmol) was suspended in
dichloromethane (1000 ml). Rhodium(ll)octanoate (0.4 g; 0.51 mmol) was added to the suspension so obtained and the reaction mixture was refluxed for 2 h. The reaction mixture was concentrated by removing dichloromethane to half of the volume and cyclohexane (500 ml) was added to the reaction mixture at 20°-25°C. The thick precipitate resulted at the end of addition was isolated by filtration and washed with cyclohexane (200 ml) to obtain the title compound (84 g). The remaining solution containing rhodium(ll)octanoate was taken for the recovery.
Step (b): Recovery of Rhodium(ll)octanoate:
The solution obtained from step (a) was concentrated and the solvent was distilled out at a temperature of 40°-45°C under reduced pressure. Toluene (300 ml) was added to the concentrated solution followed by the addition of formic acid (98% by weight formic acid; 200 ml). The reaction mixture was stirred for 10 minutes and the toluene layer was separated. The toluene layer was concentrated under reduced pressure to the volume of about 30 to 50 ml at about 45°C. The analysis of the solution by thermogravimetry showed the presence of 80% of rhodium(ll)octanoate in active form.
EXAMPLE 2
PREPARATIONOF4-NITROBENZYL(4fl,5fl,6S)-3- [(DIPHENOXYPHOSPHORYL)OXY]-6-[(1 R)-1 -HYDROXYETHYL]-4-METHYL-
7-OXO-1 -AZABICYCLO[3.2.0]HEPT-2-ENE-2-CARBOXYLATE AND
RECOVERY OF RHODIUM(II)OCTANOATE
Step (a) Preparation of 4-nitrobenzyl (4/?,5ft,6S)-3-
[(diphenoxyphosphoryl)oxy]-6-[(1 /?)-1 -hydroxyethyl]-4-methyl-7-oxo-1 -azabicyclo[3.2.0]hept-2-ene-2-carboxylate:
(3S,4R)-3-[(1R)-1-Hydroxyethyl]-4-[(1R)-1-methyl-3-diazo-3-(4-nitrobenzyloxy)carbony!-2-oxopropyl]-azetidin-2-one (100 g; 256 mmol) was dissolved in methylene chloride (1 L) followed by the addition of
rhodium(ll)octanoate (0,4 g; 0.51 mmol) and zinc bromide (0.4 g; 1.79 mmol). The solution so obtained was refluxed for 4 h. After 4 h, the reaction mixture was cooled to -10oC, followed by the addition of diphenyl chlorophosphate (80 g; 300 mmol), dimethylaminopyridine (0.3 g; 2.4 mmol) and diisopropylethylamine (40 g; 314 mmol) at 0 to -5°C. The reaction mixture was stirred at 0 to -5°C for 45 minutes. The reaction mixture was washed with 2N hydrochloric acid (500 ml), 5% sodium bicarbonate (500 ml) and water (500 ml). The organic layer was concentrated to about 500 ml and the product was crystallized by the addition of n-hexane (500 ml). The crystals were separated and dried to give the title compound (126 g). The remaining solution containing rhodium(ll)octanoate was taken for the recovery.
Step (b): Recovery of Rhodium(ll)octanoate:
Rhodium(ll)octanoate was recovered from the solution obtained in step (a) in the same manner as set forth in step (b) of Example 1. The analysis of the toluene solution so obtained showed the presence of 80% of rhodium(ll)octanoate in active form by thermogravimetry.
EXAMPLE 3
PREPARATION OF 4-NITROBENZYL (5K,6S)-6-[(1R)-1-HYDROXYETHYL]-
3J-DIOXO-1 -AZABICYCLO[3.2.0]HEPTANE-2-CARBOXYLATE WITH
RECOVERED RHODIUM(II)OCTANOATE AND FURTHER RECOVERY OF RHODIUM(II)OCTANOATE
Step (a): Preparation of 4-nitrobenzyl (5/?,6S)-6-[(1ft)-1-hydroxyethyl]-3,7-
dioxo-1-azabicyclo[3.2.0]heptane-2-carboxylate with recovered
rhodium(ll)octanoate:
(3S,4R)-3-[(1R)-Hydroxyethyl]-4-[3-(4-nitrobenzyloxy)carbonyl-2-oxo-3-diazopropyl]azetidin-2-one (100 g; 265.9 mmol) was suspended in dichloromethane (1000 ml). The rhodium(ll)octanoate solution in toluene
(obtained from step b) of Example 1) was added to the suspension so obtained
along with fresh rhodium(ll)octanoate (120 mg; 30%) and the reaction mixture
was refluxed for 2 h. After the completion of the reaction, the title compound was
isolated from the reaction in the same manner as set forth in step (a) of Example
1.
Yield: 84 g
Purity: 98% (HPLC)
Step (b): Recovery of Rhodium(ll)octanoate:
Rhodium(ll)octanoate was recovered from the solution obtained in step (a) in the same manner as set forth in step (b) of Example 1. The analysis of the toluene solution so obtained showed the presence of 70% of rhodium(ll)octanoate in active form by thermogravimetry.
EXAMPLE 4
PREPARATION OF 4-NITROBENZYL (4R,5R,6S)-3-
[(DIPHENOXYPHOSPHORYL)OXY]-6-[(1 R)-1 -HYDROXYETHYL]-4-METHYL-
7-OXO-1 -AZABICYCLO[3.2.0]HEPT-2-ENE-2-CARBOXYLATE WITH
RECOVERED RHODIUM(II)OCTANOATE AND FURTHER RECOVERY OF RHODIUM(II)OCTANOATE
Step (a) Preparation of 4-nitrobenzyl (4R,5R,6S)-3-
t(diphenoxyphosphoryl)oxy]-6-[(1R)-1-hydroxyethyl]-4-methyl-7-oxo-1-
azabicyclo[3.2.0]hept-2-ene-2-carboxylate with recovered
rhodium(ll)octanoate:
(3S,4R)-3-[(1R)-1-hydroxyethyl]-4-[(1R)-1-methyl-3-diazo-3-(4-nitrobenzyloxy)carbonyl-2-oxopropyl]-azetidin-2-one (100 g; 256 mmol) was dissolved in methylene chloride (1 L) followed by the addition of rhodium(ll)octanoate solution in toluene (280 g in 40 ml; 70%; recovered from step (b) of Example 2) along with fresh rhodium(ll)octanoate (0.12 g; 0.15 mmol)
and zinc bromide (0.4 g; 1.79 mmol). The reaction was further carried out in the same manner as set forth in step (a) of Example 2 to obtain the title compound. Yield: 118 g Purity: 98% (HPLC)
Step (b): Recovery of Rhodium(ll)octanoate:
Rhodium(ll)octanoate was recovered from the solution obtained in step a) in the same manner as set forth in step (b) of Example 2. The analysis of the toluene solution obtained showed the presence of 70% of rhodium(ll)octanoate in active form by thermogravimetry.
EXAMPLE 5 PREPARATION OF MEROPENEM:
4-nitrobenzyl (4R,5R,6S)-3-[(diphenoxyphosphoryl)oxy]-6-[(1R)-1 -hydroxyethyl]-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate (20 g) was dissolved in N-methyl-2-pyrrolidone (100 ml) and cooled to -20° to -15°C. (2S,4S)-2-[(dimethylamino)carbonyl]-4-mercaptopyrrolidine-1-carboxylate (12 g) was added to the reaction mixture followed by the drop-wise addition of diisopropylethylamine (5.6 g) at -15° to -5°C and the reaction mixture was stirred to obtain the compound of Formula IV. The formation of the product was monitored by thin layer chromatography. 5% Palladium-carbon (30 g) was added to a buffer containing N-methylmorpholine (3.4 g) and appropriate quantity of hydrochloric acid so as to obtain a pH of 6.5 to 7.0 in distilled water (120 ml). The reaction mixture containing the compound of Formula IV was added to the buffer and hydrogenated for 3 to 4 h at about 25°C. The catalyst was filtered after the completion of hydrogenation and washed with water (100 ml). The filtrate was treated with activated charcoal and acetone (1.6 L) was added to the filtrate at 0°-5°C. The reaction mixture was stirred for 6 h at 0°-5°C and the title compound was isolated in crystalline form by filtration.
Yield: 6.Og Purity: 98% (HPLC)

WE CLAIM:
1. A process for recovering the homogeneous catalyst from a catalytic reaction
mixture, which comprises,
a) treating a catalytic reaction mixture containing homogeneous catalyst and a
water immiscible organic solvent, with a C1-2alkanoic acid, and
b) recovering the homogeneous catalyst from the reaction mixture obtained in
step a) by layer separation.

2. A process as claimed in claim 1, wherein the homogeneous catalyst is a metal
containing compound or complex in which the metal is a Group VIII metal.
3. A process as claimed in claim 2, wherein the metal containing compound is
rhodium carboxylate.
4. A process as claimed in claim 1, wherein the water immiscible organic solvent
is selected from a group comprising of toluene, methylene chloride, methyl t-butyl
ether, xylene, 1,2-dichloroethane and cyclohexane.
5. A process as claimed in claim 1, wherein C1-2alkanoic acid is formic acid.
6. A process for the preparation of the compound of Formula I,
(Formula Removed)
FORMULA I
wherein PI is hydrogen or a carboxyl protecting group, P3 is hydrogen or a hydroxyl protecting group, and R1 is hydrogen or C1-3 alkyl group, or its stereoisomers, or salts thereof, wherein the said process comprises,
a) treating the compound of Formula II with a homogeneous rhodium catalyst in a water immiscible organic solvent,
(Formula Removed)
FORMULA II
wherein P1 is hydrogen or a carboxyl protecting group, P2 is hydrogen or an
amino protecting group, P3 is hydrogen or a hydroxyl protecting group, and R1 is
hydrogen or C1-3 alkyl group, to obtain the compound of Formula I,
b) isolating the compound of Formula I or its stereoisomers, or salts thereof, from
the reaction mixture thereof,
wherein step b) further comprises recovering the homogeneous rhodium catalyst
from the reaction mixture by layer separation.
7. A process as claimed in claim 6, wherein the homogeneous rhodium catalyst is rhodium(ll)octanoate.
8, A process for the preparation of the compound of Form III,
(Formula Removed)
FORMULA III
wherein P1 is hydrogen or a carboxyl protecting group, P3 is hydrogen or a hydroxyl protecting group, R1 is hydrogen or C1-3 alkyl group, and B is OP(O)(OR)2 or OSO2R, wherein R is substituted or unsubstituted C1-6 alkyl, aralkyl or aryl, or its stereoisomers, or salts thereof, wherein the said process comprises,
a) treating the compound of Formula II with a homogeneous rhodium catalyst in a water immisciole organic solvent,
(Formula Removed)
FORMULA II
wherein P1 is hydrogen or a carboxyl protecting group, P2 is hydrogen or an amino protecting group, P3 is hydrogen or a hydroxyl protecting group, and RI is hydrogen or C1-3 alkyl group, to obtain the compound of Formula I,
(Formula Removed)
FORMULA I
wherein P1, P3 and R1 are as defined above,
b) reacting the compound of Formula I with a compound of Formula X-B1,
wherein B1 is -P(O)(OR)2 or -SO2R, wherein R is substituted or unsubstituted C1-6
alkyl, aralkyl or aryl, and X is halogen, to obtain a compound of Formula III,
c) isolating the compound of Formula III or its stereoisomers, or salts thereof,
from the reaction mixture thereof,
wherein step c) further comprises recovering the homogeneous rhodium catalyst from the reaction mixture by layer separation.
9. A process for the preparation of carbapenem compounds of Formula IV,

(Formula Removed)
FORMULA IV
wherein P1 is hydrogen or a carboxyl protecting group, P3 is hydrogen or a hydroxyl protecting group, R1 is hydrogen or C1-3 alkyl group, and A is selected from a group comprising of
(Formula Removed)
wherein P2 is hydrogen or an amino protecting group, R2 and R3 are same or different and are hydrogen, C1-5 alkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl, or its stereoisomers, or salts thereof,
wherein the said process comprises,
a) treating the compound of Formula II with a homogeneous rhodium catalyst in a
water immiscible organic solvent,
(Formula Removed)
FORMULA II
wherein P1 P2, P3 and R1 are as defined above, to obtain the compound of Formula I,

(Formula Removed)

FORMULA I
wherein PI, P3 and RI are as defined above,
b) reacting the compound of Formula I with a compound of X-Bi, wherein 61 is -P(0)(OR)2 or -S02R, wherein R is substituted or unsubstituted C1-6 alkyl, aralkyi or aryl, and X is halogen, wherein R is substituted or unsubstituted C1-6 alkyl, aralkyi or aryl, and X is halogen, to obtain a compound of Formula III,
(Formula Removed)
FORMULA III
wherein P1, P3, R1 and B are as defined above, c) reacting the compound of Formula III with a compound of Formula V,
(Formula Removed)

FORMULA V
wherein A is as defined above, to obtain the compound of Formula IV
d) isolating the compound of Formula IV or its stereoisomers, or salts thereof,
from the reaction mixture thereof,
wherein the homogeneous rhodium catalyst is recovered from the reaction
mixture of step a) or step b) by layer separation.
10. A process as claimed in claim 9, wherein the compound of Formula IV is selected from a group comprising of imipenem, biapenem, meropenem, ertapenem, panipenem and doripenem.