Method for producing fluorine-containing cyclopropane carboxylic acid compound

Patent metadata

Field	Value
Publication number	US-10450291-B2
Application number	US-201615741020-A
Country	US
Kind code	B2
Filing date	Jun 24, 2016
Priority date	Jun 29, 2015
Publication date	Oct 22, 2019
Grant date	Oct 22, 2019

Abstract

The present invention provides an industrially applicable method for production of a fluorine-containing cyclopropane carboxylic acid compound useful as an intermediate for pharmaceutical and agrichemical products. A fluorine-containing cyclopropane monoester is obtained by: forming a fluorine-containing cyclic sulfate with the use of a fluorine-containing dial compound and sulfuryl fluoride (as a cyclic sulfuric esterification step); reacting the fluorine-containing cyclic sulfate with a malonic diester, thereby forming a fluorine-containing cyclopropane diester (as a cyclopropanation step); and hydrolyzing the fluorine-containing cyclopropane diester (as a hydrolysis step). The fluorine-containing cyclopropane carboxylic acid compound, such as fluorine-containing cyclopropane monoester or its salt, can be obtained with high chemical and optical purity by mixing the fluorine-containing cyclopropane monoester with an amine and subjecting the resulting salt of the fluorine-containing cyclopropane monoester and amine to recrystallization purification.

First claim

The invention claimed is:

1. A method of producing a salt of fluorine-containing cyclopropane monoester and 1-phenylethylamine as represented by the general formula [11],

where R 2 represents a C 1 -C 18 alkyl group or substituted alkyl group having a linear or branched structure or a cyclic structure (in the case of three or more carbon atoms), or a C 6 -C 18 aromatic ring group or substituted aromatic ring group; and * represents an asymmetric carbon atom,
the method comprising the following steps:
[cyclic sulfuric esterification step] reacting a fluorine-containing diol compound of the formula [12] with an alkali metal hydride, an alkali metal carbonate or an alkali metal hydrogencabonate, and sulfuryl fluoride, thereby forming a fluorine-containing cyclic sulfate of the formula [13],

where * represents an asymmetric carbon atom
[cyclopropanation step] reacting the fluorine-containing cyclic sulfate obtained in the cyclic sulfuric esterification step with a malonic diester of the general formula [3] in the presence of an alkali metal or an alkali metal hydride, thereby forming a fluorine-containing cyclopropane diester of the general formula [15]

where R 1 and R 2 each independently represent a C 1 -C 18 alkyl group or substituted alkyl group having a linear or branched structure or a cyclic structure (in the case of three or more carbon atoms), or a C 6 -C 18 aromatic ring group or substituted aromatic ring group

where R 1 and R 2 represents the same groups as defined in the general formula [3]; and * represents an asymmetric carbon atom
[hydrolysis step] hydrolyzing the fluorine-containing cyclopropane diester obtained in the cyclopropanation step in the presence of an alkali metal hydroxide, an alkali metal carbonate or a quaternary ammonium hydroxide of the general formula [6], thereby forming a fluorine-containing cyclopropane monoester of the general formula [16]

where R 3 , R 4 , R 5 and R 6 each independently represent a C 1 -C 18 alkyl group or substituted alkyl group having a linear or branched structure or a cyclic structure (in the case of three or more carbon atoms), or a C 6 -C 18 aromatic ring group or substituted aromatic ring group; and two or more of R 3 , R 4 , R 5 and R 6 may form a part of the same aliphatic ring or aromatic ring

where R 2 represents the same group as defined in the general formula [3]; and * represents an asymmetric carbon atom; and
[recrystallization step] adding optically active 1-phenylethylamine to the fluorine-containing cyclopropane monoester formed in the hydrolysis step, thereby forming a salt of the fluorine-containing cyclopropane monoester and 1-phenylethylamine as represented by the formula [11], and then, purifying the salt by recrystallization

where R 2 represents the same group as defined in the general formula [3].

2. A salt of fluorine-containing cyclopropane monoester and 1-phenylethylamine as represented by the formula [18]

where Et represents an ethyl group.

3. A salt of fluorine-containing cyclopropane monoester and 1-phenylethylamine as represented by the formula [19]

where Et represents an ethyl group.

4. The method according to claim 1 , wherein the salt represented by the general formula [11] is a salt of fluorine-containing cyclopropane monoester and 1-phenylethylamine as represented by the formula [18]

where Et represents an ethyl group.

5. The method according to claim 1 , wherein the salt represented by the general formula [11] is a salt of fluorine-containing cyclopropane monoester and 1-phenylethylamine as represented by the formula [19]

where Et represents an ethyl group.

Assignees

• Central Glass Co Ltd

Inventors

• Kashiwaba Takashi
• Yamazaki Takako
• Ishii Shoko
• Mimura Shunsuke
• Fushimi Masanori
• Okamoto Ryuichi
• Kobayashi Haruki
• Yasumoto Manabu

Classifications

• C07B57/00

  Separation of optically-active compounds · CPC title

• C07C67/313

  by introduction of doubly bound oxygen containing functional groups, e.g. carboxyl groups · CPC title

• C07D327/10 Primary

  two oxygen atoms and one sulfur atom, e.g. cyclic sulfates · CPC title

• C07C67/343

  by increase in the number of carbon atoms · CPC title

• C07C67/08

  by reacting carboxylic acids or symmetrical anhydrides with the hydroxy or O-metal group of organic compounds · CPC title