Field of the invention
The present invention provides a process for preparation of pure fluoroacrylic acid ester and preparation of its intermediate thereof.
Background of the invention
The fluoroacrylic acid ester is a key intermediate for agrochemicals and pharmaceuticals. Crossed Claisen condensation of alkyl monofluoroacetates with ester of formic acid or oxalic acid in the presence of strong bases, followed by a reaction with paraformaldehyde represents one of the most widely used methods for the synthesis of 2-fluoroacrylate.
The PCT publication no. WO 2014/034906 relates to a method for producing a-fluoroacrylic acid ester having the formula H2C=CFCO2R, wherein, R represents the alkyl group that may be substituted by one or more fluorine atoms. The a-fluoroacrylic acid ester is obtained by reacting a compound having the formula H2C=CFX, wherein X is Br or Cl, with an alcohol and carbon monoxide in the presence of a transition metal catalyst and a base.
The PCT publication no. WO 2014/001365 provides a process for the manufacture of an alkylfluoroacrylate, by reacting an alkylfluoroacetate with an ester of formic acid or oxalic acid in the presence of a base in a crossed Claisen condensation resulting in a Claisen salt. The Claisen salt is reacted with paraformaldehyde to isolate alkylfluoroacrylate, using an alkane as solvent. The process disclosed suffers from the disadvantages that the isolated methyl 2-fluoroacrylate (MFA) contains residual methyl fluoroacetate and solvents. Purification of MFA from starting material, residual solvents and side-products is difficult because of very close boiling points and careful column vacuum distillation is required. Also, the starting material methyl monofluoro acetate is highly toxic and hence there is difficulty in handling at the industrial level.
An Indian publication no. 2228/DEL/2015, has been filed by applicant of the present invention, provides an improved process for preparation of methyl 2-fluoroacrylate having high purity by reacting methyl 3-bromo-2-chloro-2-fluoropropionate with Zinc. The said process for preparation of methyl 2-fluoroacrylate is efficient and industrially attractive process. Although, applicant of the present invention observed that there is a scope to improve purity of methyl 2-fluoroacrylate by reducing the level of methyl acrylate impurity.
The methyl 3-bromo-2-chloro-2-fluoropropionate of Formula II is useful as a starting material for preparation of methyl fluoroacrylate, which is a key intermediate for agrochemicals and pharmaceuticals.

Formula II
It is therefore, an object of the present invention to provide an improved process for preparation of pure methyl 2-fluoroacrylate. The present invention provides a process for the reduction of methyl acrylate impurity in methyl 2-fluoroacrylate (MFA) of formula I which is an achievement over known method.
Object of the invention
An object of the present invention is to provide a process for preparation of compound of Formula I,

Formula I
having purity greater than 97%.

Summary of the invention
The present invention provides a process for preparation of a compound of Formula I having purity greater than 97%,

Formula I
comprising;
a) reacting the compound of Formula II,

Formula II
with zinc in the presence of defoamer to produce compound of Formula I; and
b) isolating the compound of Formula I, having purity greater than 97%, from the step a).

The present invention provides a compound of Formula I having purity greater than 97%,

Formula I
prepared by using the process of the present invention.

The present invention provides a process for preparation of a compound of Formula II,

Formula II
comprising;
a) contacting compound of Formula III,

Formula III
with metal fluoride to obtain compound of formula II, and
b) isolating the compound of Formula II from the step a).

The present invention is to provide a process for preparation of a compound of Formula II,

Formula II
comprising;
a) contacting compound of Formula III,

Formula III
with metal fluoride in the absence of solvent to obtain compound of formula I,
b) isolating the compound of Formula I from the step a).

The present invention is to provide a process for preparation of a compound of Formula II,

Formula II
comprising;
a) contacting compound of Formula III,

Formula III
with brominating agent in the presence of hydrogen fluoride to obtain a reaction mixture; and
b) isolating the compound of Formula I from the step a).
Detailed description of the invention
The present invention provides a process for preparation of a compound of Formula I having purity greater than 97%,

Formula I
comprising;
a) reacting the compound of Formula II,

Formula II
with zinc in the presence of defoamer to produce compound of Formula I; and
b) isolating the compound of Formula I, having purity greater than 97%, from the step a).
The compound of Formula I obtained by above process having purity greater than 97% analyzed by Gas Chromatography and having not more than 2 % of methyl acrylate impurity.

The step a) of the present invention may be carried out at a temperature in the range of 55oC to 100oC.
The step a) of present invention may be carried out in the presence of water and polymerization inhibitors.
The polymerization inhibitors may be selected from 2,6-bis(1,1-dimethylethyl)-4-methylphenol (BHT), methyl hydroquinone, hydroquinone, phenothiazine or other polymerization inhibitors known in the art.
A defoamer or an anti-foaming agent is a chemical additive that reduces and hinders the formation of foam in industrial process liquids. The terms anti-foam agent and defoamer are often used interchangeably.
The object of the present invention is to minimize the formation of methyl acrylate impurity in the final product by using defoamer or anti-foaming agent.
Defoamer or anti-foaming agent used in the step a) may be selected from zinc stearate, polyethylene glycol, alkyl polyacrylates, or other anti-foaming agents known in the art.
The completion of reaction may be monitored by gas chromatography or high performance liquid chromatography or thin layer chromatography.
After completion of the reaction, the final product is isolated by any isolation techniques known in the art.
Isolation of final product described here in the present invention may be effected, if desired, by any suitable separation or purification procedure such as, for example, column chromatography, distillation, azeotropic distillation, filtration, extraction, slurry wash, solvent-antisolvent system, carbon treatment or combination of these procedures.
The purification process may be used to enhance the purity of the compound and to remove the undesired impurities to acceptable limits.
The present invention provides a compound of Formula I, having purity greater than 97%, prepared by using the process of the present invention.
The compound of Formula II may be prepared by the methods of the present invention.
The present invention provides a process for preparation of a compound of Formula II by contacting compound of Formula III with metal fluoride to obtain compound of Formula II.
The compound of Formula III, used in the present invention, may be obtained commercially or may be prepared by any of the methods known in the art.
The reaction of compound of Formula III with metal fluoride is carried out in the absence of solvent and in the presence of metal chloride.
The metal fluoride may be selected from antimony trifluoride (SbF3), antimony trifluoridechloride (SbF3Cl2), stannic fluoride (SnF4), potassium fluoride (KF), zinc fluoride (ZnF2) and a like or mixture thereof.
The reaction of compound of formula III with metal fluoride may be carried out in the presence of metal chloride catalyst such as antimony pentachloride (SbCl5), antimony trichloride (SbCl3).
The reaction of compound of formula III with metal fluoride may be carried out at a temperature in the range of 140ºC to 180ºC, preferably may be carried out at a temperature of 150ºC.
The present invention provides another alternative process for preparation of a compound of Formula II by contacting compound of Formula III with brominating agent in the presence of hydrogen fluoride to obtain compound of Formula II.
The reaction may take place at a temperature range of -33ºC to 10ºC.
The brominating agents used in the reaction may be selected from bromine, bromine trifluoride, bromotrichlorornethane, carbon tetrabromide, and dibromo-dichloromethane and the like or mixture thereof. The brominating agent may be added separately or may be generated in-situ within the reaction.
The hydrogen fluoride used in the reaction is anhydrous. The hydrogen fluoride used as a solvent in the reaction.
The completion of reaction can be monitored by gas chromatography or high performance liquid chromatography or thin layer chromatography.
The compound of Formula I and intermediates thereof may be isolated by any known isolation techniques such as distillation, evaporation, decantation and layer separation or combination of said isolation techniques thereof.
The unreacted compound of Formula III, present in the product formula II, may be recycled to increase the overall yield of product.
The compound of Formula III may be obtained commercially or may be prepared by the methods known in the art.
Examples
Example 1: Preparation of methyl 3-bromo-2-chloro-2-fluoropropionate
Method 1: Methyl-2,3-dibromo-3-chloropropionate (20.8g, 0.074 mol), antimony pentachloride (1.1g, 0.007 mol) and antimony trifluoride (13.2g, 0.074 mol) were added to the reactor. Then the reactor was slowly heated to 150°C, and maintained at this temperature for 14 hours. Then the reaction mixture was poured into the cold water, filtered. The aqueous layer was extracted with dichloromethane to give the titled compound. The product was analyzed by gas chromatography which contains:
Methyl 3-bromo-2-chloro-2-fluoropropionate yield: 42.6%
Unreacted methyl-2,3-dibromo-3-chloropropionate yield: 12.5%
The unreacted methyl-2,3-dibromo-3-chloropropionate may be recycled to increase the overall yield of product.
Method 2: Methyl-2,3-dibromo-2-chloropropionate (150g, 0.54 mol) and bromine (129g, 0.81 mol) were added into reactor at 29 ºC to obtain a reaction mass. Hydrogen fluoride (107g, 5.35 mol) was added to the reaction mass at -33 ºC to -25 ºC, followed by 10% fluorine/nitrogen mixture (15.5g, 0.41 mol) was purged into that reaction mass at -10 to -5 ºC. The progress of the reaction was monitored by gas chromatography. After the completion of reaction, residual bromine in the reaction mixture were quenched using saturated sodium metabisulfite to obtain the title compound.
Yield: 65% ; Purity: 80%
Example 2: Preparation of methyl 2-fluoroacrylate (MFA)
The pre mixed mixture of Zinc (19.8g, 0.304 mol) and water (70g, 3.88 mol) were added to the mixture of methyl 3-bromo-2-chloro-2-fluoropropionate (50g, 0.229 mol), Zinc Stearate (5g, 0.008 mol) and 2,6-bis(1,1-dimethylethyl)-4-methylphenol (0.1g) in the reaction vessel with constant stirring. The reaction mixture was heated to 70°C at the constant vacuum. The product methyl 2-fluoroacrylate was azeotropically collected with water. The product was analyzed by Gas chromatography which contains
Methyl 2-fluoroacrylate: 80%
Methyl Acrylate: 0.8%
Comparative Example: Preparation of methyl 2-fluoroacrylate
Zinc (6g, 0.092 mol), water (20g, 1.11 mol), con. H2SO4 (0.2g, 0.002 mol) and phenothiazine (0.5g, 0.002 mol) were added sequentially in a reaction vessel. The reaction mixture was heated to 82°C to 86°C and methyl 3-bromo-2-chloro-2-fluoropropionate (15g, 0.068 mol) was added to the reaction mass slowly over a period of 20 minutes. An azeotropic mixture was distilled off at 55°C and 550 mbar simultaneously. Then, saturated calcium chloride (10 ml) solution was added to the azeotropic mixture and the organic layer was separated and dried to give methyl 2-fluoroacrylate as a clear colourless liquid.
Yield: 85%
Purity: 94%
Acrylate Impurity: 4-5%

WE CLAIM:
1. A process for preparation of a compound of Formula I having purity greater than 97%,

Formula I
comprising;
a) reacting the compound of Formula II,

Formula II
with zinc in the presence of defoamer to produce compound of Formula I;
b) isolating the compound of Formula I, having purity greater than 97%, from the step a).
2. The process as claimed in claim 1, wherein the step a) is carried out at a temperature in the range of 55 ºC to 100 ºC.
3. The process as claimed in claim 1, wherein the defoamer used in the step a) is selected from zinc stearate, polyethylene glycol and alkyl polyacrylates.
4. The process as claimed in claim 1, wherein the step a) is carried out in the presence of water and polymerization inhibitor selected from 2,6-bis(1,1-dimethylethyl)-4-methylphenol (BHT), methyl hydroquinone, hydroquinone and phenothiazine.
5. A process for preparation of a compound of Formula II,

Formula II
comprising;
a) contacting compound of Formula III,

Formula III
with metal fluoride to obtain compound of formula II, and
b) isolating the compound of Formula II from the step a).
6. The process as claimed in claim 5, wherein metal fluoride is selected from antimony trifluoride (SbF3), antimony trifluoridechloride (SbF3Cl2), stannic fluoride (SnF4), potassium fluoride (KF) and zinc fluoride (ZnF2) or mixture thereof.
7. The process as claimed in claim 5, wherein the step a) is carried out in the presence of metal chloride catalyst selected from antimony pentachloride (SbCl5), antimony trichloride (SbCl3).
8. A process for preparation of a compound of Formula II,

Formula II
comprising;
a) contacting compound of Formula III,

Formula III
with brominating agent in the presence of hydrogen fluoride to obtain a reaction mixture; and
b) isolating the compound of Formula I from the step a).
9. The process as claimed in claim 8, whrein the brominating agent is selected from bromine, bromine trifluoride, bromotrichlorornethane, carbon tetrabromide, and dibromo-dichloromethane; wherein the brominating agent is added separately in the reaction or may be generated in-situ within the reaction.
10. The compound of Formula I, prepared by the process as claimed in claim 1, having purity greater than 97% and having not more than 2 % of methyl acrylate impurity.