Method for industrial production of optically active fluoroalkyl ethylene oxide

Patent metadata

Field	Value
Publication number	US-10336718-B2
Application number	US-201615739498-A
Country	US
Kind code	B2
Filing date	Jun 24, 2016
Priority date	Jun 25, 2015
Publication date	Jul 2, 2019
Grant date	Jul 2, 2019

Abstract

It is possible to produce an optically active fluoroalkyl chloromethyl alcohol with a high optical purity and a good yield by treating a fluoroalkyl chloromethyl ketone with a microorganism having an activity for asymmetrically reducing the ketone or an enzyme having the activity. Then, it is possible to obtain a fluoroalkyl ethylene oxide by treating the alcohol with a base. Industrial implementation of the production method of the present invention is easy.

First claim

The invention claimed is:

1. A method for producing an optically active fluoroalkyl chloromethyl alcohol represented by formula [2]:

wherein, * represents an asymmetric atom, and Rf is defined as in formula [1],
the method comprising the step of treating a fluoroalkyl chloromethyl ketone represented by formula [1]:

wherein, Rf represents a C 1-6 straight-chain or branched-chain fluoroalkyl group having at least one fluorine atom,
with a microorganism having an activity for asymmetrically reducing the ketone or an enzyme having the activity.

2. The production method as claimed in claim 1 , wherein Rf in the fluoroalkyl chloromethyl ketone represented by formula [1] is a trifluoromethyl (CF 3 ) group or difluoromethyl (CF 2 H) group.

3. The production method as claimed in claim 1 , wherein the microorganism is at least one selected from the group consisting of Cryptococcus curvatus, Pichia farinosa, Torulaspora delbrueckii, Candida cacaoi, Rhodotorula mucilaginosa, Sporidibolus johnsonii , and Trichosporon cutaneum.

4. The production method as claimed in claim 3 , wherein the microorganism is a microorganism having a deposit number shown in the following table:

Deposit

Microorganism
number
Depositary

Cryptococcus

NBRC
National Institute of Technology and

curvatus

1159
Evaluation

Pichia farinosa

NBRC
National Institute of Technology and

0462
Evaluation

Torulaspora

NBRC
National Institute of Technology and

delbrueckii

0381
Evaluation

Candida cacaoi

NBRC
National Institute of Technology and

10231
Evaluation

Rhodotorula

NBRC
National Institute of Technology and

mucilaginosa

0001
Evaluation

Sporidibolus

NBRC
National Institute of Technology and

johnsonii

6903
Evaluation

Trichosporon

NBRC
National Institute of Technology and

cutaneum

1198
Evaluation.

5. The production method as claimed in claim 1 , wherein the enzyme is an alcohol dehydrogenase or carbonyl reductase.

6. The production method as claimed in claim 5 , wherein the alcohol dehydrogenase or carbonyl reductase is a microorganism of Tremellaceae, Saccharomycetaceae, Rhodotorula, Sporidibolus or Trichosporonaceae, a substance treated therewith, a culture thereof, and/or an enzyme obtained from the microorganism.

7. The production method as claimed in claim 1 , wherein temperature in the reaction is 5 to 60° C.

8. The production method as claimed in claim 1 , wherein pH in the reaction is in a range of 4.0 to 8.0.

9. The production method as claimed in claim 1 , comprising the step of distilling a mixed liquid containing the optically active fluoroalcohol obtained after terminating the reaction and an impurity is distilled, thereby separating the impurity from the mixed liquid and purifying the optically active fluoroalcohol.

10. A method for producing an optically active fluoroalkyl ethylene oxide represented by formula [3]:

wherein, * represents an asymmetric atom, and Rf represents a C 1-6 straight-chain or branched-chain fluoroalkyl group having at least one fluorine atom,
wherein the optically active fluoroalkyl chloromethyl alcohol represented by formula [2] is produced by the method of claim 1 , and then the alcohol is treated with a base.

11. The production method as claimed in claim 10 , wherein the base is at least one selected from the group consisting of alkali metal hydrides, alkali-earth metal hydrides, alkali metal hydroxides, alkali-earth metal hydroxides, alkali metal carbonates, alkali-earth metal carbonates, alkali metal hydrogencarbonates, and alkali-earth metal hydrogencarbonates.

12. The production method as claimed in claim 10 , further comprising the step of hydrolyzing the optically active fluoroalkyl ethylene oxide, thereby turning into a fluoroalkyl-1,2-ethanediol represented by formula [4]:

wherein, * represents an asymmetric atom, and Rf represents a C 1-6 straight-chain or branched-chain fluoroalkyl group having at least one fluorine atom.

13. The method as claimed in claim 12 , wherein the hydrolysis is conducted by a treatment with an acid or base.

14. The method as claimed in claim 13 , wherein the step of turning into the fluoroalkyl-1,2-ethanediol is conducted in the presence of the base that is at least one basic compound selected from the group consisting of alkali metal hydrides, alkali-earth metal hydrides, alkali metal hydroxides, alkali-earth metal hydroxides, alkali metal carbonates, alkali-earth metal carbonates, alkali metal hydrogencarbonates, and alkali-earth metal hydrogencarbonates.

15. The production method as claimed in claim 12 , wherein the step of turning into the fluoroalkyl-1,2-ethanediol is conducted by hydrolyzing the optically active fluoroalkyl ethylene oxide, which has been obtained by the reaction, without an isolation thereof.

16. An optically active 1-chloro-3,3-difluoroisopropyl al

Assignees

• Central Glass Co Ltd

Inventors

• Nishii Tetsuro
• Yamaguchi Ayumi
• Ootsuka Takashi
• Sawai Naoki

Classifications

• C07C29/143

  of ketones · CPC title

• C07B53/00

  Asymmetric syntheses · CPC title

• Y02P20/582

  Recycling of unreacted starting or intermediate materials · CPC title

• C12Y101/01184

  Carbonyl reductase (NADPH) (1.1.1.184) · CPC title

• C12R1/645

  Chemistry & Metallurgy · mapped topic