Method of producing optically active compound

Patent metadata

Field	Value
Publication number	US-9687833-B2
Application number	US-201414777649-A
Country	US
Kind code	B2
Filing date	Jun 3, 2014
Priority date	Jun 5, 2013
Publication date	Jun 27, 2017
Grant date	Jun 27, 2017

Abstract

An optically active compound production method using a column reactor, a column for column reactor is charged with asymmetric catalyst particles to produce the column reactor, and reaction compound is introduced into column reactor to bring reaction compound into contact with asymmetric catalyst particles, whereby reaction compound is converted to optically active compound. Asymmetric catalyst particles are preferably resin particles that are prepared from a monomer composition containing a proline derivative monomer having unsaturated bond and radical polymerization initiator and serve as catalyst for enamine mechanism reaction. Asymmetric catalyst particles are preferably resin particles prepared by micro-channel method including injecting monomer composition into continuous phase to thereby form droplets of monomer composition in continuous phase and then heating droplets to cause proline derivative monomer having an unsaturated bond to undergo radical polymerization.

First claim

The invention claimed is:

1. An optically active compound production method using a column reactor prepared by charging a column for the column reactor with asymmetric catalyst particles, wherein
the asymmetric catalyst particles have an average particle diameter of 1 to 10 μm as measured by a flow type particle image analysis method and are resin particles prepared from a monomer composition containing a monomer having a chiral source, and
a reaction compound is introduced into the column reactor to bring the reaction compound into contact with the asymmetric catalyst particles, whereby the reaction compound is converted to an optically active compound.

2. The production method according to claim 1 , wherein the asymmetric catalyst particles are resin particles prepared from a monomer composition containing, as the monomer having a chiral source, a proline derivative monomer having an unsaturated bond and further containing a radical polymerization initiator, the resin particles being capable of serving as a catalyst for an aldol reaction.

3. The production method according to claim 2 , wherein the asymmetric catalyst particles are resin particles prepared by a micro-channel method including injecting the monomer composition into a continuous phase to form droplets of the monomer composition in the continuous phase and then heating the droplets to cause the proline derivative monomer having an unsaturated bond to undergo radical polymerization.

4. The production method according to claim 2 , wherein the proline derivative monomer having an unsaturated bond is O-acryloyl-trans-4-hydroxy-L-proline, O-acryloyl-cis-4-hydroxy-L-proline, O-methacryloyl-trans-4-hydroxy-L-proline, O-methacryloyl-cis-4-hydroxy-L-proline, O-(2-methacryloyloxyethylsuccinoyl)-trans-4-hydroxy-L-proline, O-(2-methacryloyloxyethylsuccinoyl)-cis-4-hydroxy-L-proline, N-tert-butyloxycarbonyl-O-acryloyl-trans-4-hydroxy-L-proline, N-tert-butyloxycarbonyl-O-acryloyl-cis-4-hydroxy-L-proline, N-tert-butyloxycarbonyl-O-methacryloyl-trans-4-hydroxy-L-proline, N-tert-butyloxycarbonyl-O-methacryloyl-cis-4-hydroxy-L-proline, N-tert-butyloxycarbonyl-O-(2-methacryloyloxyethylsuccinoyl)-trans-4-hydroxy-L-proline, N-tert-butyloxycarbonyl-O-(2-methacryloyloxyethylsuccinoyl)-cis-4-hydroxy-L-proline, O-acryloyl-trans-4-hydroxy-D-proline,O-acryloyl-cis-4-hydroxy-D-proline, O-methacryloyl-trans-4-hydroxy-D-proline, O-methacryloyl-cis-4-hydroxy-D-proline, O-(2-methacryloyloxyethylsuccinoyl)-trans-4-hydroxy-D-proline, O-(2-methacryloyloxyethylsuccinoyl)-cis-4-hydroxy-D-proline, N-tert-butyloxycarbonyl-O-acryloyl-trans-4-hydroxy-D-proline, N-tert-butyloxycarbonyl-O-acryloyl-cis-4-hydroxy-D-proline, N-tert-butyloxycarbonyl-O-methacryloyl-trans-4-hydroxy-D-proline,N-tert-butyloxycarbonyl-O-methacryloyl-cis-4-hydroxy-D-proline, N-tert-butyloxycarbonyl-O-(2-methacryloyloxyethylsuccinoyl)-trans-4-hydroxy-D-proline, N-tert-butyloxycarbonyl-O-(2-methacryloyloxyethylsuccinoyl)-cis-4-hydroxy-D-proline, N-tert-butyloxycarbonyl-O-(4-vinylbenzyl)-trans-4-hydroxy-L-proline, N-tert-butyloxycarbonyl-O-(4-vinylbenzyl)-cis-4-hydroxy-L-proline, N-tert-butyloxycarbonyl-O-(4-vinylbenzyl)-trans-4-hydroxy-D-proline, or N-tert-butyloxycarbonyl-O-(4-vinylbenzyl)-cis-4-hydroxy-D-proline.

5. The production method according to claim 2 , wherein the proline derivative monomer having an unsaturated bond is N-tert-butyloxycarbonyl-O-(2-methacryloyloxyethylsuccinoyl)-trans-4-hydroxy-L-proline, N-tert-butyloxycarbonyl-O-(2-methacryloyloxyethylsuccinoyl)-cis-4-hydroxy-D-proline, or N-tert-butyloxycarbonyl-O-(4-vinylbenzyl)-trans-4-hydroxy-L-proline.

6. The production method according to claim 2 , wherein the monomer composition further contains a monounsaturated or polyunsaturated compound monomer.

7. The production method according to claim 2 , wherein the monomer composition further contains divinylbenzene as a polyunsaturated compound monomer.

8. The production method according to claim 2 , wherein the reaction compound comprises a carbonyl compound having an α hydrogen.

9. The production method according to claim 2 , wherein the reaction compound comprises cyclohexanone as a carbonyl compound having an α hydrogen and one of 4-nitrobenzaldehyde, 3-nitrobenzaldehyde, and 4-trifluoromethylbenzaldehyde.

10. The production method according to claim 9 , wherein the optically active compound is 2-(hydroxy(4-nitrophenyl)methyl)cyclohexan-1-one, 2-(hydroxy(3-nitrophenyl)methyl)cyclohexan-1-one, or 2-(hydroxy(4-trifluoromethylphenyl)methyl)cyclohexan-1-one.

11. The production method according to claim 1 , wherein the optically active compound converted from the reaction compound is further subjected to optical resolution in the column reactor.

12. An optically active compound production method using a column reactor prepared by charging a column for the column reactor with asymmetric catalyst particles, wherein
the asymmetric catalyst particles have an average particle diameter of 1 to 10 μm as measured by a flow type particle image analysis method and are resin particles prepared from a monomer composition containing, as a monomer having a chiral source, N-tert-butyloxycarbonyl-O-(2-methacryloyloxyethylsuccinoyl)-trans-4-hydroxy-L-proline, N-tert-butyloxycarbonyl-O-(2-methacryloyloxyethylsuccinoyl)-cis-4-hydroxy-D-proline, or N-tert-butyloxycarbonyl-O-(4-vinylbenzyl)-trans-4-hydroxy-L-proline, divinylbenzene as a polyunsaturated compound monomer, and further containing a radical polymerization initiator, the resin particles being capable of serving as a catalyst for an aldol reaction, and
a reaction compound comprising a carbonyl compound having an α hydrogen is introduced into the column reactor to bring the reaction compound into contact with the asymmetric catalyst particles, whereby the reaction compound is converted to an optically active compound.

13. An optically active compound production method using a column reactor prepared by charging a column for the column reactor with asymmetric catalyst particles, wherein
the asymmetric catalyst particles have an average particle diameter of 1 to 10 μm as measured by a flow type particle image analysis method and are resin particles prepared from a monomer composition containing, as a monomer having a chiral source, N-tert-butyloxycarbonyl-O-(2-methacryloyloxyethylsuccinoyl)-trans-4-hydroxy-L-proline, N-tert-butyloxycarbonyl-O-(2-methacryloyloxyethylsuccinoyl)-cis-4-hydroxy-D-proline, or N-tert-butyloxycarbonyl-O-(4-vinylbenzyl)-trans-4-hydroxy-L-proline, divinylbenzene as a polyunsaturated compound monomer, and further containing a radical polymerization initiator, the resin particles being capable of serving as a catalyst for an aldol reaction, and
reaction compounds comprising cyclohexanone as a carbonyl compound having an α hydrogen and one of 4-nitrobenzaldehyde, 3-nitrobenzaldehyde, and 4-trifluoromethylbenzaldehyde are introduced into the column reactor to bring the reaction compounds into contact with the asymmetric catalyst particles, whereby the reaction compounds are converted to an optically active compound, the optically active compound being 2-(hydroxy(4-nitrophenyl)methyl)cyclohexan-1-one, 2-(hydroxy(3-nitrophenyl)methyl)cyclohexan-1-one, or 2-(hydroxy(4-trifluoromethylphenyl)methyl)cyclohexan-1-one.

14. An optically active compound production method using a column reactor prepared by charging a column for the column reactor with asymmetric catalyst particles, wherein:
the asymmetric catalyst particles have an average particle diameter of 1 to 10μm as measured by a flow type particle image analysis method and are resin particles prepared from a monomer composition containing, as a m

Assignees

• Dexerials Corp

Inventors

• Kanaya Hiroki
• Nomura Mamiko

Classifications

• C07C201/12

  by reactions not involving the formation of nitro groups · CPC title

• C07C201/16

  Separation; Purification; Stabilisation; Use of additives · CPC title

• B01J31/06

  containing polymers {(organometallic polymers B01J31/123; polymer-bound organometallic complexes B01J31/165; coordination polymers B01J31/1691)} · CPC title

• B01J2208/02

  with stationary particles · CPC title

• C07C205/48

  the carbon skeleton being further substituted by singly-bound oxygen atoms · CPC title