DESC:Field of the invention
The present invention relates to a process for preparation of dialkyl alkyl phosphonite compounds.
Background of the invention:
Dialkyl alkylphosphonites, have wider industrial applications, such as in polymer industry, agrochemical industry, specialty chemicals, pharmaceuticals and other related industrial areas. The compounds such as diethyl methyl phosphonite is used as an intermediate compound in the synthesis of various final products such as Glufosinate.
The method of preparing dialkyl alkylphosphonite generally involves the use of the Grignard reagent, represented as R’MgX, wherein R’ is alkyl and X is halogen and wherein Grignard reagent as a solution in THF is reacted with dialkyl chlorophosphonite. Such methods suffer from many disadvantages during the isolation of the product. Isolation of dialkyl alkylphosphonites after the reaction requires distillation of the product. During distillation, magnesium halide such magnesium chloride, forms a complex with THF as [MgCl2(THF)]n. This complex sublimes during distillation of the dialkyl alkylphosphonite. This leads to operational problems like distillation assembly choke up leaving behind the significant amount of the product in the residue and causing lower yields due to incomplete or partial distillation of the product. Besides, cleaning the distillation assembly is an additional operation to be carried out in such cases. These methods have relatively low yield, the treatment of the residue after product isolation also results into loss of product as well as solvent which cannot be recovered.
US5128495 discloses a method of preparing dialkyl alkylphosphonites and/or monoalkyl dialkylphosphinites from the corresponding dialkyl chlorophosphonites or monoalkyl dichlorophosphinites wherein triethyl phosphite is reacted with phosphorus trichloride. The product obtained is diluted with diethylene glycol dimethylether and treated with methylmagnesium chloride in tetrahydrofuran (THF) solution to get diethyl methylphosphonite. However this process also has disadvantages like formation of magnesium chloride -THF complex, use of multiple solvents which need to be separated by cumbersome process of fractional distillation, solvent loss during residue (Residue contains solvent and MgCl2) treatment. Process operability and isolation of product is also difficult due to slurry nature of the reaction mass. Hence this process is not industrially viable.
Additionally, handling of solvent THF on larger scales is not recommended for environmental safety concern and human health hazards problems since tetrahydrofuran is in the Hazardous Substance List and regulated by Occupational Safety and Health Administration (OSHA) and the Environmental Protection Agency (EPA) . Also the danger posed by THF is its tendency to form the explosive compound 2-hydroperoxytetrahydrofuran upon reaction with air during longer storage.
Therefore, there is a need of a process for preparing dialkyl alkylphosphonites which will address above problems and will have commercial significance. Inventors of the present invention have developed a process which eliminates the drawbacks of the prior art processes and provides a simple and commercially viable process for preparation of dialkyl alkylphosphonite compounds.
Object of the invention:
Accordingly, an object of the present invention is to provide a process for the preparation of phosphorous based compound namely, dialkyl alkylphosphonite, represented by compound of Formula (I),

wherein, R and R’ can be independently selected from C1 to C8 substituted or unsubstituted alkyl or cycloalkyl group.
It is another object the present invention to provide a process of preparing dialkyl alkylphosphonite of Formula (I) which is cost effective, environment friendly and industrially viable.
Another object of the present invention is to provide a process for the preparation of dialkyl alkyl phosphonite of Formula (I), in a continuous flow reactor.

Summary of the invention:
In an aspect, the present invention provides a process for preparation of dialkyl alkylphosphonite compound of Formula (I)

wherein R and R’ are independently selected from C1 to C8 substituted or unsubstituted alkyl or cycloalkyl group;
comprising:
reacting dialkylchlorophosphite of Formula (III) with a Grignard’s reagent of Formula (IV) in a glycol ether solvent;

wherein, R , R’ are as defined above; and X is selected from Cl, Br, F or I.
In another aspect, present invention provides a process for preparation of dialkyl alkylphosphonite compound of Formula (I) in a continuous flow reactor,

wherein R and R’ are independently selected from C1 to C8 substituted or unsubstituted alkyl or cycloalkyl group;
comprising :
reacting dialkylchlorophosphite of Formula (III) with a Grignard’s reagent of Formula (IV) in a glycol ether solvent;

wherein, R , R’ are as defined above; and X is selected from Cl, Br, F or I.

In another aspect, the present invention provides a process for preparation of dialkyl alkylphosphonite compound of Formula (I),
comprising steps of:
i) reacting trialkyl phosphite of Formula (II) with phosphorus trichloride to obtain compound of formula (III)

wherein R is independently selected from C1 to C8 substituted or unsubstituted alkyl or cycloalkyl group;
ii) reacting dialkylchlorophosphite of Formula (III) with a Grignard’s reagent of Formula (IV) in a glycol ether solvent.

Detailed Description of the invention:
In order to provide a clear and consistent understanding of the terms used in the present specification, a number of definitions are provided below. Moreover, unless defined otherwise, all technical and scientific terms as used herein have the same meaning as commonly understood by the person of ordinary skill in the art to which this invention pertains.

As used in this specification the words “comprising” (and any form of comprising, such as “comprise” and “comprises”), “having” (and any form of having, such as “have” and “has”), “including” (and any form of including, such as “include” and “includes”) or “containing” (and any form of containing, such as “contain” and “contains”), are inclusive or open-ended and do not exclude additional, unrecited elements or process steps.

As used in this specification, the terms “continuous flow reactor” , “flow reactor” or “microreactor” are used interchangeably.

Accordingly, the present invention is now described with the following embodiments.

Accordingly in an embodiment, the present invention provides the process for the preparation of dialkyl alkylphosphonite compound of Formula (I),

wherein R and R’ are independently selected from C1 to C8 substituted or unsubstituted alkyl or cycloalkyl group;
comprising :
reacting dialkylchlorophosphite of Formula (III) with a Grignard’s reagent of Formula (IV) in a glycol ether solvent;

wherein, R , R’ are as defined above; and X is selected from Cl, Br, F or I.

In accordance with the above embodiment, dialkyl alkylphosphonite of Formula (I) is dialkyl methylphosphonites selected from diethyl methylphosphonite, dipropyl methylphosphonite, dibutyl methylphosphonite. In an embodiment, the compound of Formula (I) is diethyl methylphosphonite.

In accordance with the above embodiment, the compound of Formula (III) is dialkyl chlorophosphite selected from dimethyl chlorophosphite, diethyl chlorophosphite, dipropyl chlorophosphite, dibutyl chlorophosphite.

In an embodiment the compound of Formula (III) is diethyl chlorophosphite.

In an embodiment, R’MgX used for the above reaction is prepared in glycol ether solvent in which X is Cl or Br and R’ has the meaning as defined above. Preferably the R’MgX used is methylmagnesium chloride or methylmagnesium bromide, most preferably methylmagnesium chloride.

In accordance with above embodiment, the glycol ether solvent is selected from the group comprising of diethylene glycol dibutyl ether, ethylene glycol monobutyl ether, diethylene glycol monobutyl ether, the dimethyl and diethyl ethers of ethylene glycol and diethylene glycol, triethylene glycol dimethyl ether, tetraethylene glycol dimethyl ether, di-n-propyl ether, dipropyleneglycol methyl ether, ethylene glycol monopropyl ether. In an embodiment, the glycol ether solvent used is diethylene glycol dibutyl ether.

In accordance with above embodiment, the reaction is carried out at a temperature range of -10°C to 40°C.

In an embodiment, the reaction is carried out at a temperature from about 0°C to 35°C.

In another embodiment, R’MgX used for the reaction is 0.9 to 1.2 equivalent with respect to the compound of Formula (III). In an embodiment, 0.9 to 1.0 equivalent of R’MgX is used.

In accordance with the above embodiment R’MgX used for the reaction is 15% to 30 % (weight/weight) solution in glycol ether. Preferably 15% to 20 % solution is used. The reaction mixture remains a clear solution throughout the reaction.

In an embodiment, it is advantageous to use glycol ether solvent in the process which eliminates the problem of forming undesired complexes during the process, such as [MgX2(THF)]n, [R’MgX(THF)]n as in the prior art process which gets sublimated during the isolation of the product by distillation.

In an embodiment the compound of Formula (I) after completion of the reaction is isolated from the reaction mixture by distillation methods for example flash distillation, fractional distillation under vacuum at temperature in the range of 80°C to 100°C.

In an embodiment, the remaining residue after the distillation is subjected to further treatment before disposal.

In another embodiment, the present invention provides the process for the preparation of diethyl methylphosphonite of Formula (Ia)

comprising :
reacting compound of Formula (IIIa),

with methylmagnesium chloride in a glycol ether solvent.

In an embodiment, the present invention provides a process for the preparation of dialkyl alkylphosphonite compound of Formula (I) in a continuous flow reactor,

comprising :
reacting dialkylchlorophosphite of Formula (III) with a Grignard’s reagent of Formula (IV) in a glycol ether solvent;

wherein, R, R’ are as defined above; and X is selected from Cl, Br, F or I.

In an embodiment, the present process for preparing dialkyl alkylphosphonite of Formula (I) as a continuous production process, carried out in a microreactor.

In yet another embodiment, there is provided a continuous flow process for preparation of dialkyl alkylphosphonite compound of Formula (I) comprising the steps of:
a) feeding trialkylphosphite of Formula (II) to a microreactor, in a continuous flow;
b) feeding phosphorus trichloride to the microreactor, in a continuous flow;
c) feeding R’MgX to the microreactor, in a continuous flow;
d) reacting trialkylphosphite of Formula (II) and phosphorus trichloride in microreactor to form in-situ dialkyl chlorophosphite of Formula (III) ;
e) reacting dialkyl chlorophosphite of Formula (III) formed in step d) and R’MgX in a microreactor to form dialkyl alkylphosphonite of Formula (I).

In a subsequent embodiment, wherein the reaction is carried out at a temperature ranging from about 0°C to about 80°C.

In an embodiment, the process is carried out at temperature in the range of about 0°C to about 50°C and a pressure from about 1 to about 10 bar, preferably 1 to 5 bar.

In yet another embodiment, the residence time of the reaction mixture for preparing dialkyl alkylphosphonite of Formula (I) in continuous flow process is from about 30 seconds to about 5 minutes.

In an embodiment, the reaction is carried out with a flow rate of the reactants ranging from about 1ml/min to about 40 ml/min.

In an embodiment, the flow rate of phosphorus trichloride is about 1ml/min to about 15 ml/min.

In an embodiment, the flow rate of trialkyl phosphite of Formula (II) is about 1ml/min to about 25 ml/min.

In an embodiment, the flow rate of dialkylchlorophosphite of Formula (III) is about 10ml/min to about 40 ml/min.

In a prefer embodiment, preparation of dialkyl alkylphosphonite of Formula (I) occurs in shorter reaction time, as compared to the known methods.

In an embodiment, the continuous flow process for the preparation of dialkyl alkylphosphonite compound of Formula (I) is carried out in microreactors selected from the group comprising of Plug Flow Reactor (PFR), Continuous Stirred Tank Reactor (CSTR), Loop reactor, Packed Bed Reactor (PBR), static coil reactor and combinations thereof.

In an embodiment the present process in the microreactor is carried out in a solvent.

In accordance with the above embodiment the process is carried out in a glycol ether solvent.

In accordance with above embodiment, glycol ether solvent used for the reaction is selected from the group comprising of diethylene glycol dibutyl ether, ethylene glycol monobutyl ether, diethylene glycol monobutyl ether, the dimethyl and diethyl ethers of ethylene glycol and diethylene glycol, triethylene glycol dimethyl ether, tetraethylene glycol dimethyl ether, di-n-propyl ether, dipropyleneglycol methyl ether, Ethylene glycol monopropyl ether. Preferably the solvent used is diethylene glycol dibutyl ether.

In accordance with above embodiment, there is provided a continuous flow process for preparation of diethyl methylphosphonite of Formula (Ia) in a glycol ether solvent, the process comprising the steps of:
a) feeding solution of diethylchlorophosphite of Formula (IIIa) in glycol ether solvent to a microreactor, in a continuous flow;
b) feeding solution of methylmagnesium chloride in glycol ether solvent to a microreactor, in a continuous flow;
c) reacting solution of diethylchlorophosphite of Formula (IIIa) and Methylmagnesium chloride in glycol ether solvent in a microreactor to form diethyl methylphosphonite of Formula (Ia), wherein the glycol ether solvent used is diethylene glycol dibutyl ether.

In an embodiment, diethyl methylphosphonite of Formula (Ia) produced in the microreactor is then collected in a vessel connected to the microreactor.

The compound of Formula (III) is prepared according to known method by reacting trialkyl phosphite such as trimethyl phosphite, triethyl phosphite and phosphorus trichloride with or without use of catalyst.

In accordance with the above embodiment the reaction of trialkyl phosphite such as trimethyl phosphite, triethyl phosphite and phosphorus trichloride with phosphorus trichloride is carried out at 20°C to 50°C. In an embodiment, the reaction is performed at temperature in the range from 20°C to 40°C.

In an embodiment, the catalyst used is selected from the group comprising substituted phosphines dimethylbutyl-, dimethylphenyl-, dioctylphenyl- or butyldiphenylphosphine, phosphoric acid-tris-amides, such as tris-alkyl-amides, hexamethylphosphoric triamide or a quaternary ammonium salt or quaternary phosphonium salt known in the field.

In an embodiment, quaternary ammonium salt is selected from the group comprising methyltrioctylammonium chloride, tetrabutylammonium bromide, tetraethylammonium chloride, tetrabutylammonium hydrogen sulfate or the like.

In an embodiment, quaternary phosphonium salt is selected from the group comprising alkyl or aryl-substituted quaternary phosphonium salt; quaternary phosphonium salt supported on a polymer; N-alkyl substituted quaternary phosphonium salt; conjugated ion-type quaternary phosphonium salt or the likes.

In an embodiment, compound of Formula (III) is prepared by reacting trialkyl phosphite of Formula (II) and phosphorus trichloride in presence of a catalyst, wherein the reaction is carried out in a continuous flow reactor.

In an embodiment, compound of Formula (III) is prepared by reacting trialkyl phosphite of Formula (II) and phosphorus trichloride in absence of a catalyst, wherein the reaction is carried out in a continuous flow reactor.

In an embodiment, the present invention provides a process for preparation of dialkyl alkylphosphonite compound of Formula (I)
comprising steps of:
i) reacting trialkyl phosphite of Formula (II) with phosphorus trichloride to obtain compound of formula (III)

wherein R is independently selected from C1 to C8 substituted or unsubstituted alkyl or cycloalkyl group;
ii) reacting dialkylchlorophosphite of Formula (III) with a Grignard’s reagent of Formula (IV) in a glycol ether solvent.

In an embodiment, compound of Formula (II) is selected from trimethyl phosphite or triethyl phosphite.

In an embodiment, step (i) of preparing compound of Formula (III) is carried out in absence of solvent.

In an embodiment, step (i) of preparing compound of Formula (III) is carried out with or without using a catalyst.

In a subsequent embodiment, step (i) or step (ii) of the reaction is carried out in a continuous flow reactor.

In an embodiment, Grignard reagent of Formula (IV) used in step (ii) is prepared by reacting alkylhalide with magnesium in a glycol ether solvent.

In an embodiment, R’MgX is prepared in glycol ether solvent by controlled passing of alkylhalide gas, such as methyl chloride, methyl bromide in the solution of Mg turnings in glycol ether at 20°C to 90°C. In an embodiment, methyl chloride is used for the preparation of Grignard reagent.

In a subsequent embodiment the glycol ether solvent used for the preparation of R’MgX is selected from the group comprising of diethylene glycol dibutyl ether, ethylene glycol monobutyl ether, diethylene glycol monobutyl ether, the dimethyl and diethyl ethers of ethylene glycol and diethylene glycol, triethylene glycol dimethyl ether, tetraethylene glycol dimethyl ether, di-n-propyl ether, dipropyleneglycol methyl ether, ethylene glycol monopropyl ether. In an embodiment, the solvent used is diethylene glycol dibutyl ether.

In another embodiment, compound of Formula (III) and Grignard reagent of Formula (IV) prepared in the present invention are used without further purification for preparing compound of Formula (I).

In an embodiment, the present invention provides a process for preparation of diethyl methylphosphonite of Formula (Ia),

comprising steps of:
i) reacting triethyl phosphite of Formula (IIa) with phosphorus trichloride to obtain diethyl chlorophosphite of Formula (IIIa)

ii) reacting diethyl chlorophosphite of Formula (IIIa) with methylmagnesium chloride in a glycol ether solvent.

In accordance with the above embodiment, step (i) or step (ii) of the reaction is carried out in a continuous flow reactor.

In a subsequent embodiment, glycol ether solvent used for the reaction is diethylene glycol dibutyl ether.

Advantages of the present invention:
1. The present process eliminates the usage of solvents such as Tetrahydrofuran (THF) and its loss during the product isolation, leading to cost saving and preventing environmental hazards as well as human hazards.
2. The present process uses only glycol ether as a solvent which helps to keep the reaction mass a clear solution. This helps in conducting safer operation in terms of better heat transfer, better mixing, better conversion and also helps to eliminate the choking hazard during the distillation of the product.
3. The present process avoids usage of multiple solvent system and recovering the reaction solvent of the reaction upto 7 to 9 batches, making the process more economical.
4. The present process can be easily scaled up in continuous mode/flow reactor due to clear solution of the reaction mass at each stage of the reaction.

EXAMPLES
The embodiments of the present invention are illustrated by below given examples. However, the scope of the present invention is not limited by the examples.

Example 1
Preparation of diethylchlorophosphite of Formula (IIa):
Charged triethylphosphite (313.5 g; 1.8867 moles) in the reactor and hexamethylphosphoramide (1.6 g). The reaction mass was cooled to 15°C to 20°C. Phosphorus trichloride (126.5 g; 0.9212 moles) was added to obtained solution in a controlled manner in 1 hour at the same temperature and maintained for 1 to 2 hours to complete the reaction. The title product thus obtained (440 g) was then taken for next step to prepare diethyl methylphosphonite.

Example 2
Preparation of Methylmagnesium chloride (Grignard reagent):
Charged diethylene glycol dibutyl ether in a reactor (850 g/ 960 ml), followed by addition of magnesium turnings (70 g) and the reaction mass was heated to 65°C to 75°C. Purged methyl chloride gas slowly in the reaction mass at this temperature for 3 to 4 hours. Maintained reaction at 80°C to 90°C for 1 hour. The clear solution (1170 g) thus obtained was having 18 to 20 % concentration of the title compound. This solution was used in the preparation of diethyl methylphosphonite.

Example 3
Preparation of Diethyl methylphosphonite of Formula (Ia):
Charged diethylene glycol dibutyl ether (765 g/865ml) in the reactor and cooled the mass to 5°C to 10°C. Diethylchlorophosphite (440 g; 2.8110 moles) was added to the reactor to obtain a solution. Methylmagnesium chloride solution ( ? 20 %, 1083 g; 2.76 moles, prepared in diethylene glycol dibutyl ether) was then added to the above solution in a controlled manner at the same temperature in 3 to 4 hours. After completion of addition, the reaction mass temperature was raised to 20°C to 25°C and maintained for 2 hours. The reaction mass was then taken for flash distillation to get the crude product as a distillate. This distillate was then subjected to fractional distillation to get pure title compound (330 g based on PCl3) (GC purity 97.8%).

Example 4
Preparation of Diethyl methylphosphonite of Formula (Ia) in a continuous flow reactor:
35 % diethylchlorophosphite solution in diethylene glycol dibutyl ether (24.11 g; 0.0558 moles) was fed to the flow reactor at the rate of 26.06 ml/min to a continuous flow reactor to perform the reaction. 19 % solution of methylmagnesium chloride in diethylene glycol dibutyl ether (27.3 g; 0.0676 moles) was fed to the flow reactor at the rate of 28 ml/min. The mass was maintained at 10°C to 15°C to obtain diethyl methylphosphonite for residence time of 1.11 minutes.
Purity 96.85% by GC.

Example 5
Preparation of diethyl methylphosphonite of Formula (Ia) in a continuous flow reactor
Continuous flow reactor was used to perform reaction. 50 % triethylphosphite (12.48 g; 0.0373 moles) as a solution in diethylene glycol dibutyl ether was charged to the flow reactor at the rate of 13.7 ml/min. 23 % solution of phosphorus trichloride in diethylene glycol dibutyl ether (10.9 g; 0.0183 moles) was charged to the flow reactor at the rate of 11.28 ml/min. The mixture was maintained at 40°C to 45°C to form diethylchlorophosphite for residence time of 2 minutes. The resulted stream of feed 1 and feed 2 was directly charged to the flow reactor. A solution of methylmagnesium chloride in diethylene glycol dibutyl ether (19 %, 27.23 g; 0.0691 moles) was then charged to the flow reactor at the rate of 27.93 ml/min. and was maintained at 10°C to 15°C to form diethyl methylphosphonite for residence time of 1.11 minutes.

Example 6
Preparation of diethylchlorophosphite of Formula (IIa) in a continuous flow reactor
Continuous flow reactor was used to perform reaction, 50% triethylphosphite (12.46 g; 0.0374 moles) as a solution in diethylene glycol dibutyl ether was fed to the flow reactor at the rate of 13.7 ml/min. 23 % solution of phosphorus trichloride in diethylene glycol dibutyl ether (11 g; 0.0184 moles) was fed to the flow reactor at the rate of 11.4 ml/min. The reaction mass temperature was maintained at 40°C to 45°C to form diethylchlorophosphite for residence time of 2 minutes. Purity : 96.16 % by GC.

Example 7
Preparation of diethylchlorophosphite of Formula (IIa) in a continuous flow reactor
Continuous flow reactor was used to perform reaction. A solution of triethylphosphite and methyltrioctylammonium chloride having 99.49 % triethylphosphite (18.98 g; 0.1143 mmoles) was fed to the flow reactor at the rate of 20.2 ml/min. phosphorus trichloride (7.55 g; 0.055 moles) was fed to the flow reactor at the rate of 4.92 ml/min. The reaction mass temperature was maintained at 40°C to 45°C to form diethylchlorophosphite for residence time of 2 minutes. Purity : 89.7 % by GC.
,CLAIMS:
1. A process for preparation of dialkyl alkylphosphonite compound of Formula (I),

wherein R and R’ are independently selected from C1 to C8 substituted or unsubstituted alkyl or cycloalkyl group;
comprising :
reacting dialkylchlorophosphite of Formula (III) with a Grignard’s reagent of Formula (IV) in a glycol ether solvent;

wherein, R, R’ are as defined above; and X is selected from Cl, Br, F or I.

2. The process as claimed in claim 1, wherein said compound of Formula (I) is dialkyl methylphosphonites selected from diethyl methylphosphonite, dipropyl methylphosphonite, dibutyl methylphosphonite.

3. The process as claimed in claim 1, wherein said compound of Formula (III) is dialkyl chlorophosphite selected from dimethyl chlorophosphite, diethyl chlorophosphite, dipropyl chlorophosphite , dibutyl chlorophosphite.

4. The process as claimed in claim 1, wherein the glycol ether solvent is selected from the group comprising of diethylene glycol dibutyl ether, ethylene glycol monobutyl ether, diethylene glycol monobutyl ether, the dimethyl and diethyl ethers of ethylene glycol and diethylene glycol, triethylene glycol dimethyl ether, tetraethylene glycol dimethyl ether, di-n-propyl ether, dipropyleneglycol methyl ether, ethylene glycol monopropyl ether.

5. A process for preparation of dialkyl alkylphosphonite compound of Formula (I) in a continuous flow reactor,

wherein R and R’ are independently selected from C1 to C8 substituted or unsubstituted alkyl or cycloalkyl group;
comprising :
reacting dialkylchlorophosphite of Formula (III) with a Grignard’s reagent of Formula (IV) in a glycol ether solvent;

wherein, R, R’ are as defined above; and X is selected from Cl, Br, F or I.

6. The process as claimed in claim 5, wherein the reaction is carried out with a flow rate of the reactants ranging from about 1ml/min to about 40 ml/min.

7. The process as claimed in claim 5, wherein the reaction is carried out at a temperature ranging from about 0°C to about 80°C.

8. A process for the preparation of compound of Formula (Ia),

comprising :
reacting compound of Formula (IIIa),

with methylmagnesium chloride in a glycol ether solvent.

9. A process for preparation of dialkyl alkylphosphonite of Formula (I)
comprising steps of:
i) reacting trialkyl phosphite of Formula (II) with phosphorus trichloride to obtain compound of formula (III)

wherein R is independently selected from C1 to C8 substituted or unsubstituted alkyl or cycloalkyl group;
ii) reacting dialkylchlorophosphite of Formula (III) with a Grignard’s reagent of Formula (IV) in a glycol ether solvent.

10. The process as claimed in claim 9, wherein said compound of Formula (II) is selected from trimethyl phosphite or triethyl phosphite.

11. The process as claimed in claim 9, wherein step (i) of the reaction is carried out in absence of solvent.

12. The process as claimed in claim 9, wherein step (i) of the reaction is carried out with or without using a catalyst.

13. The process as claimed in claim 9 wherein step (i) or step (ii) of the reaction is carried out in a continuous flow reactor.

14. The process as claimed in claim 9 wherein said Grignard reagent used in step ii) is prepared by reacting alkylhalide with magnesium in a glycol ether solvent.