Method of producing optically active compound

{
  "publication_number": "US9687833B2",
  "country": "US",
  "kind": "B2",
  "title": "Method of producing optically active compound",
  "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.",
  "claims": [
    "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 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; and the optically active compound is further subjected to optical resolution in the column reactor.",
    "15. 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 by a micro-channel method including: injecting a monomer composition into a continuous phase to thereby form droplets of the monomer composition in the continuous phase, the 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; and then heating the droplets to cause such a proline derivative monomer having an unsaturated bond to undergo radical polymerization, the resin particles being capable of serving as a catalyst for an aldol reaction; 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; and the optically active compound is further subjected to optical resolution in the column reactor.",
    "16. A column reactor production method comprising charging a column for the column reactor and asymmetric catalyst particles, wherein the asymmetric catalyst particles used 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 proline derivative monomer having an unsaturated bond, divinylbenzene as a polyunsaturated compound monomer, and a radical polymerization initiator, the resin particles being capable of serving as a catalyst for an aldol reaction.",
    "17. The production method according to claim 16, wherein the asymmetric catalyst particles used are 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.",
    "18. A column reactor production method comprising charging a column for a column reactor with asymmetric catalyst particles, wherein the asymmetric catalyst particles used 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 by: injecting a monomer composition into a continuous phase to thereby form droplets of the monomer composition in the continuous phase, the monomer composition containing, as a proline derivative monomer having an unsaturated bond, 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; and then heating the droplets to cause the proline derivative monomer having an unsaturated bond to undergo radical polymerization, the resin particles being capable of serving as a catalyst for an aldol reaction."
  ],
  "description_excerpt": "The present invention relates to a method of producing an optically active compound using a column reactor.\n\nIt has been found that proline and derivatives thereof act as organocatalysts for organic synthesis. Particularly, proline and derivatives thereof have advantages in that an optically active proline skeleton is easily available, no metal is used, and their use environment is not limited. Proline and derivatives thereof exhibit catalytic activity for reactions useful for synthesis of raw materials of pharmaceuticals etc., such as a Michael reaction, a Diels-Alder reaction, and reactions including an aldol reaction and a Mannich reaction that proceed through an enamine mechanism, with high yield and high enantioselectivity (Non-Patent Literature 1). As for such proline derivatives, solid-phase catalysts using the proline derivatives are also known. For example, it has been proposed to obtain an asymmetric aldol reaction product in a batch process in the following manner (Non-Patent Literature 2). Resin particles obtained by suspension polymerization of a monomer composition containing an acrylate derivative monomer having a proline structure in its molecule, an unsaturated compound such as styrene or divinylbenzene, and a radical polymerization initiator are used as solid-phase asymmetric catalyst particles. The resin particles are charged into a reaction container charged with a solution in which a carbonyl compound having an α hydrogen is dissolved, and then the reaction solution mixture is heated while being mixed uniformly to thereby obtain the asymmetric aldol reaction product.",
  "cpc": [
    "B01J 31/062",
    "B01J 2208/02",
    "B01J 2231/342",
    "B01J 31/06",
    "B01J 37/00",
    "B01J 8/02",
    "C07B 2200/07",
    "C07B 53/00",
    "C07C 201/12",
    "C07C 201/16",
    "C07C 205/19",
    "C07C 205/48",
    "C07C 2101/14",
    "C07C 2601/10",
    "C07C 2601/14"
  ],
  "ipc": [
    "B01J 31/06",
    "B01J 8/02",
    "C07C 201/12",
    "B01J 31/00",
    "B01J 37/00",
    "C07B 53/00",
    "C07C 201/16",
    "C07C 205/48"
  ],
  "assignees": [
    "Dexerials Corp"
  ],
  "inventors": [
    "Hiroki Kanaya",
    "Mamiko Nomura"
  ],
  "filing_date": "2014-06-03",
  "publication_date": "2017-06-27",
  "grant_date": "2017-06-27",
  "priority_date": "2013-06-05",
  "application_number": "US-201414777649-A",
  "family_id": "52008180",
  "cited_by_count": 7,
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}