PROCESS FOR THE PREPARATION OF ALKYL HALO-SUBSTITUTED
PROPANOATE
Field of the invention
The present invention provides a process for the preparation of methyl 3-bromo-2-chloro-2-
fluoropropanoate of Formula I.
Background of the invention
The methyl 3-bromo-2-chloro-2-fluoropropanoate is useful as a starting material for the
preparation of methyl fluoroacrylate, which is a key intermediate for agrochemicals and
pharmaceuticals.
O
CH3
Cl
O
F
Br
Formula I
The present invention provides a process of preparation of methyl 3-bromo-2-chloro-2-
fluoropropanoate of Formula I which is simple, economically viable and industrially doable.
Summary of the invention
The present invention provides a process for the preparation of a compound of Formula I,
comprising;
a) reacting a compound of Formula II with bromine and bromine trifluoride to obtain the
compound of Formula I; and
b) isolating the compound of Formula I from step a).
3
O
CH3
Cl
O
F
Br
Formula I
O
CH3
Cl
O
Br
Br
Formula II
O
CH3
Cl
O
H2C
Formula III
In an aspect the present invention provides a process of preparation of a compound of
Formula I having purity greater than 96%, comprising:
a) reacting a compound of Formula III with bromine to obtain a compound of Formula
II,
b) optionally, isolating the compound of Formula II from step a),
c) contacting bromine and bromine trifluoride with step a) or b) to obtain a compound of
Formula I having purity greater than 96%, and
d) isolating the compound of Formula I having purity greater than 96% from step c).
Detailed description of the invention
The present invention provides a process for the preparation of a compound of Formula I,
comprising;
4
a) reacting a compound of Formula II with bromine and bromine trifluoride to obtain the
compound of Formula I; and
b) isolating the compound of Formula I from step a).
O
CH3
Cl
O
F
Br
Formula I
O
CH3
Cl
O
Br
Br
Formula II
O
CH3
Cl
O
H2C
Formula III
The compound of Formula II was reacted with bromine and bromine trifluoride at a
temperature in the range of 15oC to 40oC.
In an aspect the present invention provides a process of preparation of a compound of
Formula I having purity greater than 96%, comprising:
a) reacting a compound of Formula III with bromine to obtain a compound of
Formula II,
b) optionally, isolating the compound of Formula II from step a),
c) contacting bromine and bromine trifluoride with step a) or b) to obtain a
compound of Formula I having purity greater than 96%, and
d) isolating the compound of Formula I having purity greater than 96% from step c).
5
The step a) and step b) is carried out at a temperature in the range of 15oC to 40oC.
The step a) may be carried out in the presence of polymerization inhibitors such as 2,6-Bis(1,1-dimethylethyl)-4-methylphenol (BHT), methyl hydroquinone, hydroquinone, phenothiazine or other polymerization inhibitors known in the art.
The compound of Formula III may be obtained commercially or can be prepared by any of the methods known in the art, for example, as in the Japanese Patent Publication no. 61-134349.
The bromine may be in gaseous form or liquid form. The bromine utilized in present invention is greater than 90% pure. The ratio of bromine trifluoride and bromine used in the present invention is in the range of 10%:90% to 5%:95%.
The isolation of the compound of Formula I is carried out by distillation, evaporation, decantation and layer separation or mixture thereof.
The compound of Formula I, obtained by the process of the present invention has a purity greater than 97% by gas chromatography.
The compound of Formula I, as prepared by the process of the present invention, is used to prepare methyl 2-fluoroacrylate by any method known in the art.
While the present invention has been described in terms of its specific embodiments, certain modifications and equivalents will be apparent to those skilled in the art and are intended to be included within the scope of the present invention.
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 methyl 3-bromo-2-chloro-2-fluoropropanoate
6
a) Methyl-2-chloroacrylate (496 g, 4.13 mol) and BHT (3.65 g, 0.016 mol) were added into a reaction vessel fitted with a stirrer. Bromine (670 g, 4.18 mol) was added drop wise to the reaction mass over a period of 5 hours while maintaining the temperature not more than 40°C. Progress of the reaction was monitored by gas chromatography. The reaction mass was purified by distillation at 86°C and 8mm of mercury pressure to give a pale yellow liquid.
b) The step a) product (400g, 1.43mol) and 600g of Bromine were added into a reaction vessel fitted with a stirrer. Then, 1725 g of 10% of BrF3/Br2 (175g, 1.28mol) was added to the reaction mass slowly at 20°C. Progress of the reaction was monitored by gas chromatography. After completion of the reaction, the reaction mass was subjected to distillation to remove the excess bromine and washed with saturated Sodium meta-bisulfite solution to give the crude product. The crude product was further purified by distillation at 58°C and 10mm of mercury pressure to give methyl 3-bromo-2-chloro-2-fluoropropionate as a colourless liquid.
Yield: 70%
Purity : 97%

We claim:
1. A process for the preparation of a compound of Formula I, comprising;
a) reacting a compound of Formula II with bromine and bromine trifluoride to obtain the
compound of Formula I; and
b) isolating the compound of Formula I from step a).
O
CH3
Cl
O
F
Br
Formula I
O
CH3
Cl
O
Br
Br
Formula II
2. The process as claimed in claim 1, wherein step a) takes place at a temperature in the range
of 15oC to 40oC.
3. A process of preparation of a compound of Formula I having purity greater than 96%,
comprising:
a) reacting a compound of Formula III with bromine to obtain a compound of
Formula II,
b) optionally, isolating the compound of Formula II from step a),
c) contacting bromine and bromine trifluoride with step a) or b) to obtain a
compound of Formula I having purity greater than 96%, and
d) isolating the compound of Formula I having purity greater than 96% from step c).
8
O
CH3
Cl
O
H2C
Formula III
4. The process as claimed in claim 3, wherein step a) and/or step b) are carried out at a
temperature in the range of 15oC to 40oC.
5. The process as claimed in claim 3, wherein step a) is carried out in the presence of
polymerization inhibitors selected from group consisting of 2,6-Bis(1,1-dimethylethyl)-4-
methylphenol (BHT), methyl hydroquinone, hydroquinone and phenothiazine or mixture
thereof.
6. The process as claimed in claim 1 or claim 2, wherein the isolation of the compound of
Formula I is carried out by distillation, evaporation, decantation and layer separation or
mixture thereof.