Field of the invention
The present invention relates to an efficient and industrially advantageous process for purification of N-oxide pyridine derivative of formula I.

FORMULA I

Background of the invention
The N-oxide pyridine derivative is a key intermediate for agrochemicals and pharmaceuticals.
The PCT Publication No. WO2004/110351 provides a method for producing 3-trifluoromethylpyridine-N-oxide by reacting a solution of 3-trifluoromethyl pyridine in acetic acid with 20% hydrogen peroxide in water to obtain a residue. The residue thus obtained is purified by column chromatography to obtain 3-trifluoromethylpyridine-N-oxide as a yellow oil.
The said PCT publication has used column chromatography for the purification of 3-trifluoromethylpyridine-N-oxide, which is tedious purification method at industrial scale.
The PCT Publication No. WO2011/078296 provides a process for the manufacture of 3-trifluoromethylpyridine-N-oxide, by reacting 3-trifluoromethylpyridine with acetic acid and 30% hydrogen peroxide aqueous solution followed by extraction with 1,2-dichloroethane. Thereby obtained solution of 1,2-dichloroethane and 3-trifluoromethyl pyridine-N-oxide is carried forward as such for next step. The 3-trifluoromethyl pyridine-N-oxide has not isolated and hence, impurities may carry forward to the next step. The method for purifying 3-trifluoromethylpyridine-N-oxide has not been disclosed. Therefore, said process is not industrially attractive for synthesizing pure 3-trifluoromethyl pyridine-N-oxide.
The Chinese Publication No. CN103601671 provides a process for the manufacture of 3-trifluoromethylpyridine-N-oxide, by reacting 3-trifluoromethylpyridine with acetic acid and 30% hydrogen peroxide to obtain a solid. The solid thus obtained is re-crystallized from alcohol.
The said Chinese publication provide a method of recrystallizing 3-trifluoromethylpyridine-N-oxide using polar solvent, but said Chinese publication is silent about the purity of 3-trifluoromethylpyridine-N-oxide.
The present inventors have observed that in cases whrein 3-trifluoromethylpyridine-N-oxide is used as intermediate for preparing agrochemical and pharmaceutical products. The impurities introduced during commercial manufacturing processes must be limited to very small amounts, and should preferably absent.
Therefore, in view of above prior art refrences, there is a need to provide an efficient and industrially advantageous process of purification of 3-trifluoromethylpyridine-N-oxide.

Object of the invention
An object of the present invention is to provide a process for the purification of a compound of formula I.

FORMULA I

Summary of the invention
The present invention relates to a process for the purification of a compound of formula I,

FORMULA I
comprises
a) contacting a compound of formula I, having purity less than 97.2% with hydrocarbon solvent to obtain a reaction mixture;
b) optionally, heating the reaction mixture of step a);
c) optionally, cooling the reaction mixture of step b) and
d) isolating compound of formula I having purity at least 99%.

Detailed description of the invention
The present invention relates to a process for the purification of a compound of formula I.

FORMULA I
Generally, the process of purification involves contacting a compound formula I, having purity less than 97.2%, with hydrocarbon solvent to obtain a reaction mixture. Optionally, the resulting reaction mixture may be heated. Optionally, the resulting hot reaction mixture may be cooled to obtain compound of formula I. The compound formula I, having purity of at least 99%, is isolated from the reaction mixture.
The compound of formula I, having purity less than 97.2%, may be prepared by any method known in the prior art.
The hydrocarbon solvent is selected from pentane, hexane, cyclohexane, heptane, toluene, and a like or mixture thereof.
The temperature used for heating may be reflux temperature of the solvent. The reflux temperature may be refer to a temperature in the range of 36°C to 120°C. The temperature used for cooling may be in the range of 10 °C to 40°C.
The purity of compound of formula I is measured by high pressure liquid chromatography (HPLC).
The compound of formula I, having purity of at least 99%, prepared by present invention may be used to prepare 2-hydroxy-3-trifluoromethylpyridine or other agrochemicals and pharmaceuticals compounds.

EXAMPLES
Example 1: Process for the preparation of 3-trifluoromethylpyridine-N-oxide
3-Trifluoromethyl pyridine in acetic acid (37.2g, 0.25 mol) was taken in a reaction vessel and hydrogen peroxide (28%, 0.63 mole) was added drop wise at room temperature. Then reaction mass was allowed to heat at 80-85°C. The reaction progress was monitored by GC. After completion of reaction, the reaction mass was cooled to room temperature (25-30°C) and excess hydrogen peroxide was quenched by sodium sulphite. Acetic acid and water in reaction mixture was removed under reduced pressure. The above reaction mass was basified with aqueous sodium hydroxide (30%). The reaction mass was extracted with dichloromethane, organic layer was dried over anhydrous sodium sulphate and concentrated to get crude 29g of 3-trifluoromethyl pyridine-N-oxide having purity 97.18% by HPLC.

Example 2: Process for purification of 3-trifluoromethylpyridine-N-oxide
3-Trifluoromethylpyridine-N-oxide (29g) was contacted with hexane to obtain a reaction mixture. The reaction mixture was heated at reflux temperature ( 70-90°C) and then the reaction mass was cooled at room temperature to obtain 3-trifluoromethyl pyridine-N-oxide. The titled compound was isolated, having 27.4g of yield and having purity of 99.62% by HPLC.

WE CLAIM:
1. A process for the purification of compound of formula I,

FORMULA I
comprises
a) contacting compound of formula I, having purity less than 97.2% with hydrocarbon solvent to obtain a reaction mixture;
b) optionally, heating the reaction mixture of step a);
c) optionally, cooling the reaction mixture of step b) and
d) isolating compound of formula I having purity of at least 99% from the reaction mixture.

2. The process as claimed in claim 1, wherein in step a) the hydrocarbon solvent is selected from pentane, hexane, cyclohexane, heptane, toluene and mixture thereof.

3. The process as claimed in claim 1, wherein in step b) the heating temperature is reflux temperature of the solvent.

4. The process as claimed in claim 3, wherein the reflux temperature is a temperature in the range of 36°C to 120°C.

5. The process as claimed in claim 1, wherein the reaction mixture of step c) is cooled at a temperature in the range of 10 °C to 40°C.
6. The compound of formula I, purified by the process as claimed in claim 1, is used to prepare 2-hydroxy-3-trifluoromethylpyridine or other agrochemicals and pharmaceuticals compounds.

Dated this 27th day of February 2017.

Kapil
Senior Research Associate
SRF Limited