WO2016128999A1 - Process of preparation of compounds having chf 2c(o) group - Google Patents

Process of preparation of compounds having chf 2c(o) group Download PDF

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Publication number
WO2016128999A1
WO2016128999A1 PCT/IN2016/050052 IN2016050052W WO2016128999A1 WO 2016128999 A1 WO2016128999 A1 WO 2016128999A1 IN 2016050052 W IN2016050052 W IN 2016050052W WO 2016128999 A1 WO2016128999 A1 WO 2016128999A1
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WIPO (PCT)
Prior art keywords
formula
compound
preparation
chf
group
Prior art date
Application number
PCT/IN2016/050052
Other languages
French (fr)
Inventor
Vaidyanatha Swamy RAMAMOORTHY
Sarathy IYENGAR
Prasannakumar SEETHARAMAN
Radha KUMARASAMY
Raguraman TRICHY SRINIVASAN
Kapil Kumar
Rajdeep Anand
Original Assignee
Srf Limited
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Srf Limited filed Critical Srf Limited
Publication of WO2016128999A1 publication Critical patent/WO2016128999A1/en

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C67/00—Preparation of carboxylic acid esters
    • C07C67/14—Preparation of carboxylic acid esters from carboxylic acid halides

Definitions

  • the present invention relates to the process of preparation of compounds having CHF 2 C(0) group .
  • the U.S. Patent Application No. 2007/0191632 describes a process involving reduction of esters of chlorodifluoroacetic acid with zinc to produce difluoroacetic acid ester. It is further known that the esters of difluoroacetic acid can also be prepared by treating difluoroacetic acid with alcohol in presence of mineral acids such as sulphuric acid or phosphoric acid.
  • the above process suffers from the drawback that the starting material chlorodifluoroacetic acid ester as well as difluoroacetic acid are readily not available. Furthermore, in case of reduction of chlorodifluoroacetic acid ester, the reaction generates zinc waste, thus making it industrially unfavorable.
  • the present inventors have observed that carrying out the reaction of difluoroacetic acid fluoride with ethanol at 50°C makes the reaction unsafe due to the rapid and uncontrolled expulsion of HF gas.
  • the present inventors observed that upon considerable lowering of reaction temperature, the same reaction proceeds to give favourable results without compromising the safety aspects, thus making it more industrially viable.
  • An object of the present invention is to provide a process for the preparation of compound of Formula I,
  • R is selected from hydrogen and Ci-Ce alkyl group
  • the present invention provides a process for the preparation of compound of Formula I, comprising;
  • R is selected from hydrogen and Ci-Ce alkyl group
  • X is selected from fluorine, chlorine, bromine and iodine
  • R is selected from hydrogen and Ci-Ce alkyl group
  • step b) isolating compound of Formula I from the reaction mixture of step wherein step a) takes place at a temperature of not more than about 15°C.
  • the present invention provides a process for the preparation of compound of Formula I, comprising;
  • X is selected from fluorine, chlorine, bromine and iodine
  • R is selected from hydrogen and Ci-Ce alkyl group
  • step b) isolating compound of Formula I from the reaction mixture of step a), wherein step a) takes place at a temperature of not more than about 15°C.
  • the compound of Formula II may be prepared by any method known in the art, for example, known in the Indian Patent No. 262804 or U.S. Patent No. 5,710,317.
  • the step a) is carried out at a temperature of about 8°C to about 15°C, for about 3 hours to about 7 hours.
  • the compound of Formula I is isolated by any of the methods in the art, for example, evaporation, distillation and layer separation or mixture thereof.
  • the compound of Formula I as obtained by present invention, has purity of about 98% to about 99%.
  • the compound of Formula I may be ethyl difluoroacetate.
  • the term 'about' refers to a variation of 10% on the higher and lower side of specified parameter.
  • the difluoroacetyl fluoride (65g) was passed through two towers containing 3 lg ethanol in each at a temperature of 8°C to 10°C at a rate of 16g to 25g per hour till the first tower depletes to level of 0.1% of ethanol by gas chromatography area.
  • the reaction mass in first tower was distilled to separate hydrogen fluoride and ethyl difluoroacetate. Now, the second tower becomes the first tower and new tower containing fresh ethanol was introduced and the process was continued to obtain the title compound.

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

Abstract

The present invention relates to the process of preparation of compounds having CHF2C(O) group.

Description

PROCESS OF PREPARATION OF COMPOUNDS HAVING
CHF2C(0) GROUP
Field of Invention
The present invention relates to the process of preparation of compounds having CHF2C(0) group .
Background of Invention
The U.S. Patent Application No. 2007/0191632 describes a process involving reduction of esters of chlorodifluoroacetic acid with zinc to produce difluoroacetic acid ester. It is further known that the esters of difluoroacetic acid can also be prepared by treating difluoroacetic acid with alcohol in presence of mineral acids such as sulphuric acid or phosphoric acid. The above process suffers from the drawback that the starting material chlorodifluoroacetic acid ester as well as difluoroacetic acid are readily not available. Furthermore, in case of reduction of chlorodifluoroacetic acid ester, the reaction generates zinc waste, thus making it industrially unfavorable.
The U.S. Patent No. 5,710,317 describes a process for the preparation of ethyl difluoroacetate by reacting difluoroacetic acid fluoride with ethanol at 50°C.
The present inventors have observed that carrying out the reaction of difluoroacetic acid fluoride with ethanol at 50°C makes the reaction unsafe due to the rapid and uncontrolled expulsion of HF gas. The present inventors observed that upon considerable lowering of reaction temperature, the same reaction proceeds to give favourable results without compromising the safety aspects, thus making it more industrially viable.
Object of the Invention
An object of the present invention is to provide a process for the preparation of compound of Formula I,
Figure imgf000003_0001
Formula I
Wherein R is selected from hydrogen and Ci-Ce alkyl group
Summary of the Invention
The present invention provides a process for the preparation of compound of Formula I, comprising;
Figure imgf000003_0002
Formula I
Wherein R is selected from hydrogen and Ci-Ce alkyl group
a) reacting compound of Formula II with compound of Formula III, and
Figure imgf000003_0003
Formula II Formula III
where X is selected from fluorine, chlorine, bromine and iodine; R is selected from hydrogen and Ci-Ce alkyl group
b) isolating compound of Formula I from the reaction mixture of step wherein step a) takes place at a temperature of not more than about 15°C. Detailed Description of the Invention
In an aspect, the present invention provides a process for the preparation of compound of Formula I, comprising;
Figure imgf000004_0001
Formula I a) reacting compound of Formula II with compound of Formula III to obtain a reaction mixture, and
Figure imgf000004_0002
Formula II Formula III
where X is selected from fluorine, chlorine, bromine and iodine; R is selected from hydrogen and Ci-Ce alkyl group
b) isolating compound of Formula I from the reaction mixture of step a), wherein step a) takes place at a temperature of not more than about 15°C.
The compound of Formula II may be prepared by any method known in the art, for example, known in the Indian Patent No. 262804 or U.S. Patent No. 5,710,317. The step a) is carried out at a temperature of about 8°C to about 15°C, for about 3 hours to about 7 hours. The compound of Formula I is isolated by any of the methods in the art, for example, evaporation, distillation and layer separation or mixture thereof.
The compound of Formula I, as obtained by present invention, has purity of about 98% to about 99%. The compound of Formula I may be ethyl difluoroacetate. The term 'about' refers to a variation of 10% on the higher and lower side of specified parameter.
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.
Example
Preparation of Ethyl difluoroacetate
The difluoroacetyl fluoride (65g) was passed through two towers containing 3 lg ethanol in each at a temperature of 8°C to 10°C at a rate of 16g to 25g per hour till the first tower depletes to level of 0.1% of ethanol by gas chromatography area. After completion of addition, the reaction mass in first tower was distilled to separate hydrogen fluoride and ethyl difluoroacetate. Now, the second tower becomes the first tower and new tower containing fresh ethanol was introduced and the process was continued to obtain the title compound.
Yield (%): 85
Purity (%): 99.5

Claims

We claim:
1. A process for the preparation of compound of Formula I, comprising:
Figure imgf000006_0001
Formula I where R is selected from hydrogen and Ci-Ce alkyl group a) reacting compound of Formula II with compound of Formula III to obtain a reaction mixture, and
Figure imgf000006_0002
Formula II Formula III where X is selected from fluorine, chlorine, bromine and iodine; R is selected from hydrogen and Ci-Ce alkyl group
b) isolating compound of Formula I from the reaction mixture of step a), wherein step a) takes place at a temperature of not more than about 15°C.
2. The process as claimed in claim 1, wherein the step a) is carried out at a temperature in the range of 8°C to 15°C.
3. The process as claimed in claim 1, wherein the step a) is carried out for a time period in the range of 3 hours to about 7 hours.
4. The process as claimed in claim 1, wherein the isolation of compound of Formula I is carried out by evaporation, distillation and layer separation or mixture thereof.
5. The compound of Formula I, as obtained from process as claimed in claim 1, having purity of about 98% to about 99%.
PCT/IN2016/050052 2015-02-11 2016-02-11 Process of preparation of compounds having chf 2c(o) group WO2016128999A1 (en)

Applications Claiming Priority (2)

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IN393/DEL/2015 2015-02-11
IN393DE2015 2015-02-11

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN109336767A (en) * 2018-11-26 2019-02-15 山东永浩新材料科技有限公司 A kind of dehydration synthetic method of ethyl difluoro

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0694526A1 (en) * 1994-07-27 1996-01-31 Rohm And Haas Company Process for preparation of fluorinated beta-keto ester
WO2006005612A1 (en) * 2004-07-14 2006-01-19 Syngenta Participations Ag Process for the preparation of 4,4-difluoro-3-oxobutanoic acid esters

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0694526A1 (en) * 1994-07-27 1996-01-31 Rohm And Haas Company Process for preparation of fluorinated beta-keto ester
WO2006005612A1 (en) * 2004-07-14 2006-01-19 Syngenta Participations Ag Process for the preparation of 4,4-difluoro-3-oxobutanoic acid esters

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN109336767A (en) * 2018-11-26 2019-02-15 山东永浩新材料科技有限公司 A kind of dehydration synthetic method of ethyl difluoro

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