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Practical Method For Manufacturing 3 3 Difluoro 2 Hydroxypropionic Acid

Abstract: 2Provided is a practical method for manufacturing 3 3 difluoro 2 hydroxypropionic acid which is important as an intermediate for medical and agricultural chemicals. By reacting a 4 4 difluoro 3 oxobutanoic acid ester with chlorine (Cl) a 4 4 difluoro 2 2 dichloro 3 oxobutanoic acid ester is obtained. By then reacting with an acid 3 3 difluoro 1 1 dichloro 2 propanone is obtained. Finally by reacting with a basic aqueous solution 3 3 difluoro 2 hydroxypropionic acid can be manufactured.

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Patent Information

Application #
Filing Date
11 September 2017
Publication Number
41/2017
Publication Type
INA
Invention Field
CHEMICAL
Status
Email
Parent Application
Patent Number
Legal Status
Grant Date
2019-12-31
Renewal Date

Applicants

CENTRAL GLASS COMPANY LIMITED
5253 Oaza Okiube Ube shi Yamaguchi 7550001

Inventors

1. YAMAZAKI Takako
c/o Chemical Research Center of CENTRAL GLASS COMPANY LIMITED 17 5 Nakadai 2 chome Kawagoe shi Saitama 3501159
2. OKAMOTO Ryuichi
c/o Chemical Research Center of CENTRAL GLASS COMPANY LIMITED 17 5 Nakadai 2 chome Kawagoe shi Saitama 3501159
3. ISHII Akihiro
c/o Chemical Research Center of CENTRAL GLASS COMPANY LIMITED 17 5 Nakadai 2 chome Kawagoe shi Saitama 3501159

Specification

Entitled practical production method of 3,3-difluoro-2-hydroxypropionic acid Technical field [0001] The present invention relates to a practical method for producing 3,3-difluoro-2-hydroxypropionic acid. Background technique [0002] 3,3-difluoro-2-hydroxypropionic acid is an important compound as a pharmaceutical and agrochemical intermediates. For example, can be easily derived from the compound 3,3-difluoro-2-hydroxypropionic acid amide, they are used as intermediates for phosphodiesterase 10 inhibitors (Patent Document 1). [0003] As a typical preparation method of 3,3-difluoro-2-hydroxypropionic acids, there is a method oxidation decomposing furan skeleton (Non-patent Document 1). [0004] As a conventional technique related to the chlorination step of the present invention, the 4,4,4-trifluoro-3-oxobutanoic acid ester from 4,4,4-trifluoro-2,2-dichloro-3-oxobutanoic acid ester there is a method for producing (Patent Document 2, non-Patent Document 2). [0005] As the prior art related to reducing coal process of the present invention, 3,3,3-trifluoro-1,1 from 4,4,4-trifluoro-2,2-dichloro-3-oxobutanoic acid ester there is a method of producing a dichloro-2-propanone (Patent Document 2). [0006] Further, as the prior art related to the pressurized alkali decomposition process of the present invention, 3,3,3 trifluoromethoxy 1,1-dichloro-2-propanone 3,3,3-trifluoro-2-hydroxypropionic acid there is a method of producing the (Patent Document 3). CITATION Patent Document [0007] Patent Document 1: International Publication Patent Publication No. 2014-078220 Patent Document 2: Laid-Open Publication No. 9-227440 Patent Document 3: Laid-Open Patent Publication No. 2004-018503 Non-patent literature [0008] Non-Patent Document 1: Cryst Eng Comm (UK), 2006, Vol. 8, p. 320-326 Non-Patent Document 2: Tetrahedron (Netherlands), 2009, Vol. 65, p. 7538-7552 Disclosure of the Invention Problems that the Invention is to Solve [0009] The method according to Non-Patent Document 1, the number of reaction steps were not longer practical. [0010] An object of the present invention, medical important 3,3-difluoro-2-hydroxy acid as a pesticide intermediates, under mild reaction conditions which can be employed industrially, short steps and high productivity over the prior art in is to manufacture. Means for Solving the Problems [0011] The present inventors have made intensive studies to solve the above problems, 4,4-difluoro-3-oxobutanoate ester by reaction with chlorine gas 4,4-difluoro-2,2-dichloro -3 - converted into oxobutanoic acid ester, by subsequently reacted with an acid to give 3,3-difluoro-1,1-dichloro-2-propanone, by finally reacting with a basic aqueous solution 3,3-difluoro 2-hydroxypropionic acid was newly found can be produced. The present invention consists of three steps shown in Scheme 1, the first step chlorination step, the second step Gensumi step, the third step is a pressurized alkaline decomposition process. Further, as useful intermediates in the production process of the present invention, 4,4-difluoro-2,2-dichloro-3-oxobutanoic acid ester of the novel compounds was also newly found. [Formula 1] [0012] In each step employed in the present invention, when comparing with Patent Document 2 and Patent Document 3 and Non-Patent Document 2, there has been chemically it is expected from problems. [0013] For example, the invention is described in Patent Document 2, and severe reaction conditions are employed in the chlorination step, and the ester moiety is also considerably chlorinated as a side reaction (see the following scheme). 4,4-difluoro-3-oxobutanoate ester as the starting material substrate of the invention, the 4-position and further comprising a hydrogen atom, alpha-position proton of the carbonyl group, are recognized as likely functional group is halogenated there. Therefore, employing the reaction conditions of Patent Document 2 as it is, in the raw substrate material of the present invention, to think that even 4-position as well as the ester moiety is chlorinated are common. In the industrial practice, the amount of chlorine gas is increased by side reactions, undesirable from the standpoint of cost and chlorinated waste. Of course, the purification operation is also complicated due to the purity of the desired product. [Formula 2] [0014] Further, Patent Document 2, harsh reaction conditions also in reducing coal process has been adopted in the industrial practice, there is a material limitations and a large amount of waste sulfuric acid treatment problem for high temperature reactions. [0015] The invention described in Non-Patent Document 2, a relatively expensive sulfuryl chloride as the chlorinating agent is used in large excess, it is moderate yield even by further long reaction time. Further with diethyl ether special flammables as the reaction solvent. [0016] Patent Document 3, the raw material substrate is 3,3,3-trifluoro-1,1-dichloro-2-propanone, is an object of the present invention 3,3-difluoro-1,1-dichloro-2-propanone the difference revealed structural features (see the following scheme). Comparing the both sides of the substituent of the carbonyl group, whereas in the substrate of Patent Document 3 is a clear area to be alkali decomposition pressure (CF 3 groups

Documents

Application Documents

# Name Date
1 201737031998-TRANSLATIOIN OF PRIOIRTY DOCUMENTS ETC. [11-09-2017(online)].pdf 2017-09-11
2 201737031998-STATEMENT OF UNDERTAKING (FORM 3) [11-09-2017(online)].pdf 2017-09-11
3 201737031998-PROOF OF RIGHT [11-09-2017(online)].pdf 2017-09-11
4 201737031998-POWER OF AUTHORITY [11-09-2017(online)].pdf 2017-09-11
5 201737031998-FORM 1 [11-09-2017(online)].pdf 2017-09-11
6 201737031998-DECLARATION OF INVENTORSHIP (FORM 5) [11-09-2017(online)].pdf 2017-09-11
7 201737031998-COMPLETE SPECIFICATION [11-09-2017(online)].pdf 2017-09-11
8 201737031998-FORM 18 [18-09-2017(online)].pdf 2017-09-18
9 201737031998-FORM 3 [02-02-2018(online)].pdf 2018-02-02
10 201737031998-FER.pdf 2019-04-29
11 201737031998-FORM 3 [31-05-2019(online)].pdf 2019-05-31
12 201737031998-PETITION UNDER RULE 137 [14-10-2019(online)].pdf 2019-10-14
13 201737031998-OTHERS [14-10-2019(online)].pdf 2019-10-14
14 201737031998-MARKED COPIES OF AMENDEMENTS [14-10-2019(online)].pdf 2019-10-14
15 201737031998-FORM 13 [14-10-2019(online)].pdf 2019-10-14
16 201737031998-FER_SER_REPLY [14-10-2019(online)].pdf 2019-10-14
17 201737031998-COMPLETE SPECIFICATION [14-10-2019(online)].pdf 2019-10-14
18 201737031998-CLAIMS [14-10-2019(online)].pdf 2019-10-14
19 201737031998-AMMENDED DOCUMENTS [14-10-2019(online)].pdf 2019-10-14
20 201737031998-ABSTRACT [14-10-2019(online)].pdf 2019-10-14
21 201737031998-HearingNoticeLetter-(DateOfHearing-19-12-2019).pdf 2019-12-04
22 201737031998-Correspondence to notify the Controller (Mandatory) [16-12-2019(online)].pdf 2019-12-16
23 201737031998-Written submissions and relevant documents (MANDATORY) [20-12-2019(online)].pdf 2019-12-20
24 201737031998-PatentCertificate31-12-2019.pdf 2019-12-31
25 201737031998-IntimationOfGrant31-12-2019.pdf 2019-12-31
26 201737031998-PROOF OF ALTERATION [05-05-2021(online)].pdf 2021-05-05
27 201737031998-RELEVANT DOCUMENTS [25-09-2021(online)].pdf 2021-09-25
28 201737031998-RELEVANT DOCUMENTS [29-07-2022(online)].pdf 2022-07-29
29 201737031998-RELEVANT DOCUMENTS [27-07-2023(online)].pdf 2023-07-27

Search Strategy

1 SearchStrategy201637031998_29-04-2019.pdf

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