Practical method for manufacturing 3,3-difluoro-2-hydroxypropionic acid

Patent metadata

Field	Value
Publication number	US-10273200-B2
Application number	US-201615551640-A
Country	US
Kind code	B2
Filing date	Mar 15, 2016
Priority date	Mar 27, 2015
Publication date	Apr 30, 2019
Grant date	Apr 30, 2019

Abstract

Disclosed is a practical method for production of 3,3-difluoro-2-hydroxypropionic acid, which is important as pharmaceutical and agrichemical intermediates. The method includes forming a 4,4-difluoro-2,2-dichloro-3-oxobutanoic acid ester by reaction of a 4,4-difluoro-3-oxobutanoic acid ester with chlorine (Cl2), forming 3,3-difluoro-1,1-dichloro-2-propanone by reaction of the chlorination product with an acid, and then, reacting the degradation product with a basic aqueous solution.

First claim

The invention claimed is:

1. A method for producing 3,3-difluoro-2-hydroxypropionic acid of the formula [4]

the method comprising the following steps:
[first step] reacting a 4,4-difluoro-3-oxobutanoic acid ester of the general formula [1] with chlorine, thereby forming a 4,4-difluoro-2,2-dichloro-3-oxobutanoic acid ester of the general formula [2]

where R is a C 1 -C 6 alkyl group;

where R is a C 1 -C 6 alkyl group;
[second step] reacting the 4,4-difluoro-2,2-dichloro-3-oxobutanoic acid ester with an acid, thereby forming 3,3-difluoro-1,1-dichloro-2-propanone of the formula [3]

and
[third step] reacting the 3,3-difluoro-1,1-dichloro-2-propanone with a basic aqueous solution to obtain the 3,3-difluoro-2-hydroxypropionic acid of the formula [4]
wherein the first step includes: converting the 4,4-difluoro-3-oxobutanoic acid ester of the general formula [1] to a 4,4-difluoro-2-chloro-3-oxobutanoic acid ester of the general formula [5] by reaction with chlorine in the absence of water; and then, converting the 4,4-difluoro-2-chloro-3-oxobutanoic acid ester to the 4,4-difluoro-2,2-dichloro-3-oxobutanoic acid ester of the general formula [2] by reaction with chlorine in the presence of water

where R is a C 1 -C 6 alkyl group.

2. The method according to claim 1 , wherein the acid used in the second step is an acidic aqueous solution.

3. The method according to claim 1 , wherein the first step is performed at a reaction temperature of +50 to −30° C.

4. The method according to claim 2 , wherein the acidic aqueous solution has a concentration of 0.3 to 90%.

5. The method according to claim 2 , wherein the acid reacted with the 4,4-difluoro-2,2-dichloro-3-oxobutanoic acid ester in the second step is hydrogen chloride remaining the 4,4-difluoro-2,2-dichloro-3-oxobutanoic acid ester after the first step.

6. The method according to claim 1 , wherein the second step is performed at a reaction temperature of +135 to 0° C.

Assignees

• Central Glass Co Ltd

Inventors

• Yamazaki Takako
• Okamoto Ryuichi
• Ishii Akihiro

Classifications

• C07C59/115

  containing halogen · CPC title

• C07C49/16

  containing halogen · CPC title

• C07C51/295

  with inorganic bases, e.g. by alkali fusion · CPC title

• C07C67/307 Primary

  by introduction of halogen; by substitution of halogen atoms by other halogen atoms · CPC title

• C07C69/716

  Esters of keto-carboxylic acids {or aldehydo-carboxylic acids} · CPC title