The present invention provides an improved process for the preparation of halogenated esters of Formula I,

Formula I
wherein R1 is independently selected from hydrogen, alkyl, halogenated alkyl; R2 is alkyl; X1, X2 and Z can be halogen, halogenated alkyl group.

BACKGROUND OF THE INVENTION
Cyclopropane carboxylic acid derivatives are very useful intermediate for pharmaceuticals or agrochemicals.
US Patent No. 4,332,815 describes a process for preparation of ethyl 3,3-dimethyl-4,6,6-trichloro-7,7,7-trifluoroheptanoate by reacting ethyl 3,3-dimethyl-4-pentenoate with 1,1,1-trichlorotrifluoroethane in t-butanol in presence of ethanolamine and cuprous chloride. The process is very exothermic and sudden increase in the heat of reaction pose safety concerns at commercial scale up. The exothermicity induces degradation and thereby reduces the yield and purity of the final product.
Thus with this state of the art in mind, there is need to provide improved process over the existing one. The present invention provides a simple, safe and improved cost effective method for preparing intermediates of cyclopropane carboxylic acid.

OBJECT OF THE INVENTION
The main object of present invention is to provide an industrially viable process for the preparation of halogenated ester that are useful intermediates for preparation of cyclopropane carboxylic acid derivatives.

SUMMARY OF THE INVENTION
A first aspect of present invention provides an improved process for preparation of intermediates of cyclopropane carboxylic acid of Formula I,

Formula I
wherein R1 is independently selected from hydrogen, alkyl, halogenated alkyl; R2 is alkyl; X1, X2 and Z can be halogen, halogenated alkyl group,
comprising the step of adding a mixture of compound of Formula II and an organic ligand in a polar solvent,

Formula II
wherein R1 is independently selected from hydrogen, alkyl, halogenated alkyl,
to a mixture of a compound of formula III and a catalyst in a polar organic solvent,

Formula III
wherein, X1, X2 and Z can be halogen, halogenated alkyl group,
to obtain a compound of Formula I.
A second aspect of present invention provides an improved process for preparation of intermediates of cyclopropane carboxylic acid of Formula I,

Formula I
wherein R1 are independently selected from hydrogen, alkyl, halogenated alkyl; R2 is alkyl; X1, X2 and Z can be halogen, halogenated alkyl group,
comprising the step of:
a) adding a compound of Formula II and an organic ligand in a polar solvent,

Formula II
wherein R1 are independently selected from hydrogen, alkyl, halogenated alkyl,
to a mixture of a compound of formula III and catalyst in a polar organic solvent,

wherein, X1, X2 and Z can be halogen, alkyl, halogenated alkyl group,
b) isolating the compound of formula I using polymeric solvents.

DETAILED DESCRIPTION OF THE INVENTION
As used herein, “alkyl” refers to C1-C2 alkyl. Examples of alkyl include methyl, ethyl or the like.
As used herein, “catalyst” refers to metal ions and neutral metallic species. Suitable catalysts include cuprous salts, organometallic cuprous compounds, iron wire, iron shavings, iron powder, and iron chlorides. Examples of cuprous salts and organometallic cuprous compounds include, without limitation, cuprous chloride (CuCl), cuprous bromide, cuprous cyanide, cuprous sulfate, cuprous phenyl and in-situ generated organometallic cuprous compounds. The iron powder useful in this invention is preferably a fine powder of pure metallic iron. Preferably, cuprous chloride or iron powder is used as the catalyst.
As used herein, “an organic ligand” refers to organic ligands capable of forming a complex with the catalyst and capable of bringing the catalyst into solution. Suitable ligands include organic amines, such as, without limitation, ethanolamine, N,N,N'.N'-tetramethylethylenediamine diethanolamine, propanolamine, pyridine tert-butylamine, n-butylamine, sec-butylamine, 2-propylamine, benzylamine, tri-n-butylamine, pyridine and combinations thereof.
As used herein, “solvent” refers to a polar organic such as alcohols, ethers, nitriles, or the like. Suitable solvent includes acetonitrile, ethanol, methanol, butanol, t-butanol, n-pentanol, iso-pentanol, t-pentanol, tetrahydrofuran or the like
As used herein, “polymeric solvent” includes polyhydric solvents and “polyamines”. Examples of polyhydric alcohol includes glycerol, chloroethylene glycol, dimethyl ether of diethylene glycol, ethoxy ether, ethylene glycol, propylene glycol, polyethylene glycol, polypropylene glycol, polytetramethylene glycol or polytetramethylene ether glycol, Examples of polyamine includes diethylenetriamine, triethylenetetramine, pentaethylenehexamine, tetraethylenepentamine, Macrocyclic polyamines, 1,4,7-triazacyclononane or the like.
In an embodiment of the present invention, the mixture of compound of Formula II and an organic ligand is added to a mixture of a compound of formula III and a catalyst, slowly in a controlled manner to maintain the heat of reaction between 80°C to 110°C.
This reaction is highly exothermic, the heat of the reaction generated is so high that it leads to run-away condition in the plant scale in case of normal addition of all the raw materials. So, in such cases, raw materials are added in controlled manner in order to control the heat of the reaction and make the process safer.
In an embodiment of the present invention, the mixture of compound of Formula II and an organic ligand is added to a mixture of a compound of formula III and a catalyst, slowly in a controlled manner to maintaining the temperature of reaction between 80°C to 110°C.
In an embodiment of the present invention, the compound of Formula II and an organic ligand are separately added to a mixture of a compound of formula III and a catalyst, slowly in a controlled manner to maintain the heat of reaction under control.
In another embodiment of the present invention, the product is isolated using a dry work up. In a preferred embodiment the dry work up is performed in absence of water using polymeric solvent.
Isolation is conventionally carried out by two methods, firstly, using hydrochloride solution during work-up, this method generates the aqueous effluent containing spent catalyst. Secondly, product isolation is carried out via decantation that leaves behind the spent catalyst in the reactor requiring large quantities of hydrochloric acid for its removal, thereby generating large quantities of aqueous effluent containing the catalyst. Both the methods generate large quantity of effluent that require expensive and tedious effluent treatment for removal of catalyst. On the other hand, polymeric solvents, can be easily recycled and reused, thereby generating very little catalytic effluent that can be easily incinerated or get rid of in a cost-effective way.
In another embodiment of the present invention, the “polyhydric solvent” and “polyamines” used in the work up is recovered and recycled.
In another embodiment of the present invention, the product is isolated using an aqueous hydrochloric acid work up.
In another embodiment of the present invention, the product is isolated by direct decantation of product.
In another embodiment of the present invention, the product is isolated by direct distillation and separation of product.
In another embodiment of the present invention, the organic solvent and the compound of formula III used in excess is recovered and recycled in the process.
The dry work up ensure the efficient effluent treatment and management in the process at commercial scale.
In another embodiment of the present invention, the solvent used is recovered, recycled and reused.
In an embodiment of the present invention, the process resulted in the formation of an alcohol as a by-product that is recovered and recycled.
In a particular embodiment, the present invention provides an improved process for preparation of methyl 4,6,6-trichloro-7,7,7-trifluoro-3,3-dimethylheptanoate comprising the steps of slowly adding a mixture of methyl 3,3-dimethyl-4-pentenoate and ethanolamine in t-butanol to a mixture of 1,1,1-trichloro-2,2,2-trifluoro ethane and copper chloride in t-butanol to obtain methyl 4,6,6-trichloro-7,7,7-trifluoro-3,3-dimethylheptanoate.
In an embodiment of the present invention, the step of slowly adding a mixture of methyl 3,3-dimethyl-4-pentenoate and ethanolamine in t-butanol to a mixture of 1,1,1-Trichloro-2,2,2-trifluoro ethane and copper chloride in t-butanol is carried out at a temperature below 100-120°C, within a time period of 12 to 15 hours.
In another particular embodiment of the present invention, the butanol is recovered and recycled.
In another particular embodiment of the present invention, methyl 4,6,6-trichloro-7,7,7-trifluoro-3,3-dimethylheptanoate was isolated using dry work up being carried out in absence of water.
In another particular embodiment of the present invention, methyl 4,6,6-trichloro-7,7,7-trifluoro-3,3-dimethylheptanoate was isolated using polyhydric alcohol or polyamines.
The compound of Formula I is isolated by using techniques known in the art for example distillation, evaporation, column chromatography and layer separation or combination thereof.
The compound of Formula I so obtained by the present invention has a purity greater than 95 %, more preferably greater than 98 %, most preferably greater than 99.6 % by gas chromatography.
Unless stated to the contrary, any of the words “comprising”, “comprises” and includes mean “including without limitation” and shall not be construed to limit any general statement that it follows to the specific or similar items or matters immediately following it.
Embodiments of the invention are not mutually exclusive, but may be implemented in various combinations. The described embodiments of the invention and the disclosed examples are given for the purpose of illustration rather than limitation of the invention as set forth in the appended claims.
The following example is given by way of illustration and therefore should not be construed to limit the scope of the present invention.

EXAMPLES
Example 1: Process for preparation of methyl 4,6,6-trichloro-7,7,7-trifluoro-3,3-dimethylheptanoate
A solution of methyl 3,3-dimethyl-4-pentenoate (500g) and ethanolamine (26g) in t-butanol (78g) was added to a solution of 1,1,1-trichloro-2,2,2-trifluoroethane (879g) and copper chloride (35.5g) in t-butanol (261g) at 80-100°C. The reaction mixture was stirred at 80-100°C for 10 hours. The progress of the reaction was monitored by Gas chromatography and after completion of the reaction, the excess of 1,1,1-trichloro-2,2,2-trifluoroethane and t-butanol was distilled out under reduced pressure for further reuse. The reaction mass was cooled and washed with an aqueous hydrochloric acid (10%). The layers were separated, to obtain the titled compound.
Yield: 96%
Purity: 95%
Example 2: Process for preparation of methyl 4,6,6-trichloro-7,7,7-trifluoro-3,3-dimethylheptanoate
A solution of methyl 3,3-dimethyl-4-pentenoate (500g) and ethanolamine (26g) in t-butanol (78g) was added to a solution of 1,1,1-trichloro-2,2,2-trifluoroethane (879g) and copper chloride (35.5g) in t-butanol (261g) at 80-100°C. The reaction mixture was stirred at 80-100°C for 10 hours. The progress of the reaction was monitored by Gas chromatography and after completion of the reaction, the excess of 1,1,1-trichloro-2,2,2-trifluoroethane and t-butanol was distilled out under reduced pressure for further reuse. The reaction mass was cooled and triethylenetetramine was added to it. The mixture was stirred for one hour, and separate the layers to obtain the titled compound.
Yield: 96%
Purity: 97%
Example 3: Process for preparation of methyl 4,6,6-trichloro-7,7,7-trifluoro-3,3-dimethylheptanoate
A solution of ethanolamine (26g) in t-butanol (78g) and methyl 3,3-dimethyl-4-pentenoate (500g) were concurrently added to a solution of 1,1,1-trichloro-2,2,2-trifluoroethane (879g) and copper chloride (35.5g) in t-butanol (261g) at 80-100°C. The reaction mixture was stirred at 80-100°C for 10 hours. The progress of the reaction was monitored by Gas chromatography and after completion of the reaction, the excess of 1,1,1-trichloro-2,2,2-trifluoroethane and t-butanol was distilled out under reduced pressure for further reuse. The reaction mass was cooled and decanted-off to obtain the titled compound.
Yield: 96%
Purity: 98%
Example 4: Process for preparation of methyl 4,6,6-trichloro-7,7,7-trifluoro-3,3-dimethylheptanoate
A solution of copper chloride (35.5g) with ethanolamine (26g) in t-butanol (78g) and methyl 3,3-dimethyl-4-pentenoate (500g) were concurrently added to a solution of 1,1,1-trichloro-2,2,2-trifluoroethane (879g) in t-butanol (261g) at 80-100°C. The reaction mixture was stirred at 80-100°C for 10 hours. The progress of the reaction was monitored by Gas chromatography and after completion of the reaction, the excess of 1,1,1-trichloro-2,2,2-trifluoroethane and t-butanol was distilled out under reduced pressure for further reuse. The reaction mass left was cooled and polypropylene glycol was added to it. The mixture was stirred for 3 hours, and layers were separated, to obtain the titled compound.
Yield: 97%
Purity: 99%
Example 5: Process for preparation of methyl 4,6,6-trichloro-7,7,7-trifluoro-3,3-dimethylheptanoate
A solution of 1,1,1-trichloro-2,2,2-trifluoroethane (879g) and ethanolamine (26g) in t-butanol (78g) was added to a solution of methyl 3,3-dimethyl-4-pentenoate (500g) and copper chloride (35.5g) in t-butanol (261g) at 80-100°C. The reaction mixture was stirred at 80-100°C for 10 hours. The progress of the reaction was monitored by Gas chromatography and after completion of the reaction, the excess of 1,1,1-trichloro-2,2,2-trifluoroethane and t-butanol was distilled out under reduced pressure for further reuse. The reaction mass left was cooled and polypropylene glycol was added to it. The mixture was stirred for 3 hours, and layers were separated, to obtain the titled compound.
Yield: 96%
Purity: 95%
Example 6: Process for preparation of methyl 4,6,6-trichloro-7,7,7-trifluoro-3,3-dimethylheptanoate
A solution of copper chloride (35.5g) with ethanolamine (26g) in t-butanol (78g) and methyl 3,3-dimethyl-4-pentenoate (500g) were concurrently added to a solution of 1,1,1-trichloro-2,2,2-trifluoroethane (879g) in t-butanol (261g) at 80-100°C. The reaction mixture was stirred at 80-100°C for 10 hours. The progress of the reaction was monitored by Gas chromatography and after completion of the reaction, the excess of 1,1,1-trichloro-2,2,2-trifluoroethane and t-butanol was distilled out under reduced pressure for further reuse. The reaction mass left was cooled and ethylene glycol was added to it. The mixture was stirred for 3 hours, and layers were separated, to obtain the titled compound.
Yield: 96%
Purity: 95%

Example 7: Process for preparation of methyl 4,6,6-trichloro-7,7,7-trifluoro-3,3-dimethylheptanoate
A solution of 1,1,1-trichloro-2,2,2-trifluoroethane (879g) and ethanolamine (26g) in t-butanol (78g) was added to a solution of methyl 3,3-dimethyl-4-pentenoate (500g) and copper chloride (35.5g) in t-butanol (261g) at 80-100°C. The reaction mixture was stirred at 80-100°C for 10 hours. The progress of the reaction was monitored by Gas chromatography and after completion of the reaction, the excess of 1,1,1-trichloro-2,2,2-trifluoroethane and t-butanol was distilled out under reduced pressure for further reuse. The reaction mass left was cooled and propylene glycol was added to it. The mixture was stirred for 3 hours, and layers were separated, to obtain the titled compound.
Yield: 96%
Purity: 95%
Example 8: Process for preparation of methyl 4,6,6,6-tetrachloro-3,3-dimethylhexanoate
A solution of methyl 3,3-dimethyl-4-pentenoate (500g) and ethanolamine (26g) in t-butanol (78g) was added to a solution of tetrachloromethane (700g) and copper chloride (35.5g) in t-butanol (261g) at 80-100°C. The reaction mixture was stirred at 80-100°C for 10 hours. The progress of the reaction was monitored by Gas chromatography and after completion of the reaction, the excess of 1,1,1-trichloro-2,2,2-trifluoroethane and t-butanol was distilled out under reduced pressure for further reuse. The reaction mass left was cooled and washed with an aqueous hydrochloric acid (10%). The layers were separated, the organic layer was distilled to obtain the titled compound.
Yield: 95%
Purity: 99%

Example 9: Process for preparation of Methyl 4,6,6-trichloro-7,7,7-trifluoro-3,3-dimethylheptanoate
Charged copper chloride (35.5g), ethanolamine (26g) and t-butanol (261g) and stirred for 1 hour. After in-situ preparation of catalyst concurrently charged a solution of 1,1,1-trichloro-2,2,2-trifluoroethane (879g) in t-butanol (78g) and 3,3-dimethyl-4-pentenoate (500g) at 80-100°C. The reaction mixture was further stirred at 80-100°C for 10 hours. The progress of the reaction was monitored by Gas chromatography and after completion of the reaction, the excess of 1,1,1-trichloro-2,2,2-trifluoroethane and t-butanol was distilled out under reduced pressure for further reuse. The reaction mass left was cooled and washed with an aqueous hydrochloric acid (10%). The layers were separated, the organic layer was distilled to obtain the titled compound.
Yield: 99%
Purity: 98%
Example 10 (Comparative; without controlled conditions): Process for preparation of Methyl 4,6,6-trichloro-7,7,7-trifluoro-3,3-dimethylheptanoate
A solution of methyl 3,3-dimethyl-4-pentenoate (500g) and ethanolamine (26g) in t-butanol (78g) was added to a solution of 1,1,1-trichloro-2,2,2-trifluoroethane (879g) and copper chloride (35.5g) in t-butanol (261g). The reaction mixture was stirred for 10 hours. The progress of the reaction was monitored by Gas chromatography and after completion of the reaction, the excess of 1,1,1-trichloro-2,2,2-trifluoroethane and t-butanol was distilled out under reduced pressure for further reuse. The reaction mass was cooled and washed with an aqueous hydrochloric acid (10%). The layers were separated, to obtain the titled compound.
Yield: 66%; Purity: 75%;
The exothermicity of the reaction is not controlled that leads to the degradation of the intermediate and formation of impurities.

WE CLAIM:

1. A process for preparation of a compound of formula I,

Formula I
wherein R1 is independently selected from hydrogen, alkyl, halogenated alkyl; R2 is alkyl; X1, X2 and Z is selected from halogen, halogenated alkyl group,
comprising the step of adding a mixture of a compound of formula II and an organic ligand in a polar solvent,

Formula II
wherein R1 is independently selected from hydrogen, alkyl, halogenated alkyl,
to a mixture of a compound of formula III and a catalyst in a polar solvent,

Formula III
wherein, X1, X2 and Z is selected from halogen, halogenated alkyl group,
to obtain a compound of formula I.
2. The process as claimed in claim 1, wherein the compound of formula I is isolated using polymeric solvents.

3. The process as claimed in claim 1, wherein the “catalyst” is selected from a group consisting of cuprous salts, organometallic cuprous compounds, iron and iron chloride.
4. The process as claimed in claim 1, wherein the “organic ligand” is an organic amine selected from a group consisting of ethanolamine, N,N,N'.N'-tetramethylethylenediamine, diethanolamine, propanolamine, pyridine tert-butylamine, n-butylamine, sec-butylamine, 2-propylamine, benzylamine, tri-n-butylamine and pyridine or a combinations thereof.
5. The process as claimed in claim 2, wherein the “polymeric solvent” is a polyhydric solvent or a polyamine solvent selected from a group consisting of glycerol, chloroethylene glycol, dimethyl ether of diethylene glycol, ethoxy ether, ethylene glycol, propylene glycol, polyethylene glycol, polypropylene glycol, polytetramethylene glycol, polytetramethylene ether glycol, diethylenetriamine, triethylenetetramine, pentaethylenehexamine, tetraethylenepentamine, macrocyclic polyamines and 1,4,7-triazacyclononane or a mixture thereof.
6. The process as claimed in claim 1, wherein the mixture of compound of formula II and an organic ligand is added to a mixture of a compound of formula III and a catalyst, slowly in a controlled manner to maintain the heat of reaction under control.
7. The process as claimed in claim 1, wherein the compound of formula II and an organic ligand are separately added to a mixture of a compound of formula III and a catalyst, slowly in a controlled manner to maintain the heat of reaction under control.
8. The process as claimed in claim 1, wherein the product is isolated using a dry work up.
9. The process as claimed in claim 1, wherein the polar solvent is an alcohol, ether or a nitrile selected from a group consisting of acetonitrile, ethanol, methanol, butanol, t-butanol, n-pentanol, iso-pentanol, t-pentanol and tetrahydrofuran or a mixture thereof.

10. The process as claimed in claim 1, wherein the excess of solvent used is recovered and recycled.