The present invention provides a process for preparing 2-fluoro-haloalkylpyridines of Formula I, which are useful as intermediates for pharmaceuticals and agrochemicals industries.

Formula I
wherein n represents an integer 1 or 2; m and o independently represents an integer from 0-5.

BACKGROUND OF THE INVENTION
The present invention relates to a novel 2-fluoro-haloalkylpyridines compound as an intermediate from which a compound effective in controlling various harmful organisms or an effective component compound of medicines can be easily derived, and a process for preparing the same.
Its application is very extensive, combined with the difficulty of synthesis, has been unable to achieve industrial production, the market price has been high. Therefore, the industrial production of 2-fluoro-4-chlorodifluoromethylpyridine has become an urgent problem to be solved.
EP Patent No. 0063872 discloses a preparation of fluoro methylpyridines where at least one of the halo groups attached to the ring is ortho or para to the fluoromethyl group of the compound. The process involves the fluorination of the corresponding chloro methylpyridine using potassium fluoride in a polar aprotic solvent under anhydrous conditions in the presence of phase transfer catalyst to give product having fluorination of ring as well as fluorination of chloromethyl side chain. The process is not suited for the preparation of the fluorinated pyridine compounds where only ring fluorination is desirable.
An object of the present invention is to provide a process for selective halogen exchange of 2-chloro-4-halomethylpyridine to give 2-fluoro-4-halomethylpyridine.
The present invention provides a commercially and economically viable process for large scale industrial manufacturing of 2-fluoro-4-halomethylpyridines with high purity and yield.

OBJECT OF THE INVENTION
The main object of present invention is to provide an industrially applicable process for the preparation of 2-fluoro-haloalkylpyridines with a high reaction rate and high selectivity.

SUMMARY OF THE INVENTION
The present invention provides a process for preparation compound of Formula I,

Formula I
wherein n represents an integer 1 or 2; m and o independently represents an integer from 0-5,
comprising the step of fluorination of pyridine compound of Formula II;

Formula II
wherein n and m are as defined above; X is either of chlorine or bromine,

with a fluorinating agent in presence of a polar aprotic solvent.

DETAILED DESCRIPTION OF THE INVENTION
As used herein, the ‘fluorinating agent’ is selected from alkali metal fluoride such as potassium fluoride sodium fluoride, tetrabutylammonium fluoride or the like. Preferably, the fluorinating agent is a mixture of potassium fluoride and a catalytic amount of cesium fluoride.
In an embodiment of the present invention, the amount of alkali metal fluoride used in the process ranges from 1.1 to 3.8 equivalent.
In another embodiment of the present invention, the amount of cesium fluoride used in the process ranges from 0.001 to 0.1 equivalent.
As used herein, the polar aprotic solvent is selected from dimethylsulfoxide (DMSO), sulfolane, N-dimethylformamide (DMF), N-methyl-2-pyrrolidone (NMP), dimethylsulfone, hexamethylphosphoric triamide or a mixture thereof.
In an embodiment of the present invention, the polar aprotic solvent is the one having large dielectric constant.
As used herein, polar aprotic solvent having large dielectric constant is selected from a polar aprotic solvent or a mixture thereof having dielectric constant of more than 43, when measured at a temperature of 25°C.
In a preferred embodiment of the present invention, dimethylsulfoxide is used as a solvent.
In preferred embodiment of the present invention, the process does not involve use of any phase transfer catalyst.
In another preferred embodiment of the present invention, the process does not involve use of any co-solvents such as hydrocarbons and halogenated hydrocarbons, for example, toluene, xylene, kerosene and the complex mixture of aromatic hydrocarbons as specified in EP Patent No. 0063872.
In another embodiment of the present invention, 2-halo-haloalkylpyridine may be further substituted with a group selected from halogen, cyano, alkyl or the like.
In an another embodiment of the present invention, the fluorination reaction is carried out at temperatures in the range 120°C to 140°C.
In another embodiment of the present invention, the 2-fluoro-halomethylpyridine obtained is substantially pure and free from the impurities generated due to side chain halogen exchange and decomposition.
As used herein, the term substantially pure refer to the product having purity of more than 90%, preferably having purity between 90-99%.
In another embodiment of the present invention, the process is carried out in a corrosion resistant reactor.
In another embodiment of the present invention, the corrosion resistant reactor comprised of materials which are resistant to corrosion as Hastelloy, Inconel, Monel and/or fluoropolymers linings.
In an embodiment, the present invention provides a process for the preparation of 2-fluoro-4-difluorochloromethylpyridine comprising the steps of fluorination of 2-halo-4-difluorochloromethylpyridine using fluorinating agent.
In another embodiment, the present invention provides a process for the preparation of 2-fluoro-4-dichlorofluoromethylpyridine comprising the steps of fluorination of 2-halo-4-dichlorofluoromethylpyridine using fluorinating agent.
In a preferred embodiment, the present invention provides a process for the preparation of 2-fluoro-4-dichloromethylpyridine comprising the steps of fluorination of 2-halo-4-dichloromethylpyridine using fluorinating agent.
As used herein, the term “isolate” refers to a method of chemical separation, extraction, acid-base neutralization, distillation, evaporation, column chromatography and filtration or crystallization or a combination thereof.
Unless stated to the contrary, any of the words “comprising”, “comprises” 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 completion of the reaction can be monitored by any one of chromatographic techniques such as thin layer chromatography (TLC), high pressure liquid chromatography (HPLC), ultra-pressure liquid chromatography (UPLC), Gas chromatography (GC) and alike.
The following examples are given by way of illustration and therefore should not be construed to limit the scope of the present invention.

EXAMPLES
Example 1: Preparation of 2-fluoro-4-chlorodifluoromethylpyridine
2-chloro-4-chlorodifluoromethylpyridine (185.0g, 0.89mol, purity-95%), anhydrous potassium fluoride (215.0g, 3.7mol), cesium fluoride (14.0g, 0.09mol) and dimethylsulfoxide (1000.0g, 12.8mol) were charged in a Hastelloy reactor (2000ml) and the reaction mixture was heated to 140°C and maintained at the same temperature for 8 hours. After completion of the reaction, reaction mass was transferred to round bottomed flask containing water. Thereafter the product was isolated by distillation along with water. Organic layer was separated out from the distillate to obtained 2-fluoro-4-chlorodifluromethylpyridine (147.0g).
Purity: 92.4%; Yield: 84%
2-fluoro-4-trifluromethylpyridine: less than 6%
2-chloro-4-trifluromethylpyridine: less than 2%
Example 2: Preparation of 2-fluoro-4-dichlorofluoromethylpyridine
2-bromo-4-dichlorofluoromethylpyridine (0.9mol, purity-95%), anhydrous potassium fluoride (3.8mol), cesium fluoride (0.1mol) and dimethylsulfoxide (12.8mol) were charged in a Hastelloy reactor (2000ml) and the reaction mixture was heated up to 140°C and maintained the reaction temperature for 7 hours. After completion of the reaction, reaction mass was transferred to round bottomed flask containing water. Thereafter the product was isolated by distillation along with water. Organic layer was separated out from the distillate to obtain 2-fluoro-4-dichlorofluoromethylpyridine.
Purity: 94.6%; Yield: 76%
2-fluoro-4-trifluromethylpyridine: less than 6%
2-fluoro-4-chlorodifluromethylpyridine: less than 3%
Example 3: Preparation of 2-fluoro-4-dichloromethylpyridine
2-chloro-4-dichloromethylpyridine (1.0mol, purity-92%), anhydrous potassium fluoride (3.8mol), cesium fluoride (0.1mol) and dimethylsulfoxide (12.8mol) were charged in a Hastelloy reactor (2000ml)and the reaction mixture was heated up to 135°C and maintained the reaction temperature for 8 hours. After completion of the reaction, reaction mass was transferred to round bottomed flask containing water. Thereafter the product was isolated by distillation along with water. Organic layer was separated out from the distillate to obtain 2-fluoro-4-dichloromethylpyridine.
Purity: 92.6% Yield: 62%
2-fluoro-4-difluromethylpyridine: less than 6%
2-chloro-4-difluromethylpyridine: less than 2%

WE CLAIM:

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

Formula I
wherein n represents an integer 1 or 2; m and o independently represents an integer from 0-5,
comprising the step of fluorination of compound of Formula II;

Formula II
wherein n and m are as defined above; X is chlorine or bromine.
with a fluorinating agent in presence of a polar aprotic solvent.
2. The process as claimed in claim 1, wherein the fluorination is carried out using a fluorinating agent and a catalytic amount of cesium fluoride.
3. The process as claimed in claim 1 and 2, wherein the fluorinating agent is selected from a group consisting of alkali metal fluoride and tetrabutylammonium fluoride.
4. The process as claimed in claim 3, wherein the amount of alkali metal fluoride is in the range of 1.1 to 3.8 mole equivalents.
5. The process as claimed in claim 2, wherein the amount of cesium fluoride ranges from 0.001 to 0.1 mole equivalents.
6. The process as claimed in claim 1, wherein the polar aprotic solvent is selected from a group consisting of dimethyl sulfoxide (DMSO), sulfolane, N-dimethyl formamide (DMF), N-methyl-2-pyrrolidone (NMP), dimethyl sulfone and hexamethylphosphoric triamide or a mixture thereof.
7. The process as claimed in claim 1, wherein the polar aprotic solvent has dielectric constant of more than 43 at a temperature of 25°C.
8. The process as claimed in claim 1, wherein the reaction is carried out without using any phase transfer catalyst.
9. The process as claimed in claim 1, wherein the fluorination reaction is carried out at temperatures in the range of 120°C to 140°C.
10. The process as claimed in claim 1, wherein the compound of formula I is obtained with a purity of more than 90%.