METHOD OF PRODUCING OPTICALLY ACTIVE ß-AMINOCARBONYL COMPOUND

Patent metadata

Field	Value
Publication number	US-2016159729-A1
Application number	US-201514939571-A
Country	US
Kind code	A1
Filing date	Nov 12, 2015
Priority date	Dec 3, 2014
Publication date	Jun 9, 2016
Grant date	—

Abstract

In a method of producing an optically active β-aminocarbonyl compound using a column reactor, a column for a column reactor is charged with asymmetric catalyst particles to form a column reactor. Compounds for a Mannich-type reaction are introduced into the column reactor to be brought into contact with the asymmetric catalyst particles, to thereby convert the compounds to an optically active β-aminocarbonyl compound. The preferable asymmetric catalyst particles are resin particles that are prepared from a monomer composition containing a proline derivative monomer having an unsaturated bond and a radical polymerization initiator, and that act as a catalyst for an asymmetric Mannich-type reaction.

First claim

The invention claimed is:

1 . A method of producing an optically active β-aminocarbonyl compound by an asymmetric Mannich-type reaction using a column reactor in which a column is charged with asymmetric catalyst particles, wherein
the asymmetric catalyst particles are resin particles prepared from a monomer composition containing a monomer having an asymmetric source, and

the method comprises introducing compounds for a Mannich-type reaction into the column reactor to bring the compounds into contact with the asymmetric catalyst particles, to thereby convert the compounds for a Mannich-type reaction to an optically active β-aminocarbonyl compound.

2 . The method of producing an optically active β-aminocarbonyl compound according to claim 1 , wherein the asymmetric catalyst particles are resin particles that are prepared from a monomer composition containing a proline derivative monomer having an unsaturated bond as a monomer having an asymmetric source and a radical polymerization initiator, and that act as a catalyst for an asymmetric Mannich-type reaction.

3 . The method of producing an optically active β-aminocarbonyl compound according to claim 1 , wherein the asymmetric catalyst particles are resin particles that are prepared through a microchannel method in which the monomer composition is discharged into a continuous phase to form droplets of the monomer composition in the continuous phase, and the droplets are heated to radically polymerize the proline derivative monomer having an unsaturated bond.

4 . The method of producing an optically active β-aminocarbonyl compound according to claim 1 , wherein the proline derivative monomer having an unsaturated bond is one selected from the group consisting of 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, and N-tert-butyloxycarbonyl-O-(4-vinylbenzyl)-cis-4-hydroxy-D-proline.

5 . The method of producing an optically active β-aminocarbonyl compound according to claim 1 , wherein the proline derivative monomer having an unsaturated bond is one selected from the group consisting of N-tert-butyloxycarbonyl-O-(2-methacryloyloxyethylsuccinoyl)-trans-4-hydroxy-L-proline, N-tert-butyloxycarbonyl-O-(2-methacryloyloxyethylsuccinoyl)-cis-4-hydroxy-D-proline, and N-tert-butyloxycarbonyl-O-(4-vinylbenzyl)-trans-4-hydroxy-L-proline.

6 . The method of producing an optically active β-aminocarbonyl compound according to claim 1 , wherein the monomer composition further contains any of a monovalent unsaturated compound monomer and a polyvalent unsaturated compound monomer.

7 . The method of producing an optically active β-aminocarbonyl compound according to claim 1 , wherein the monomer composition further contains divinylbenzene as a polyvalent unsaturated compound monomer.

8 . The method of producing an optically active β-aminocarbonyl compound according to claim 1 , wherein the compounds for a Mannich-type reaction include an amine compound represented by the formula (1), an aldehyde compound that reacts with the amine compound to produce an imine compound or an iminium cation compound and is represented by the formula (2), and a carbonyl compound having an α-hydrogen that is converted into an enol compound that reacts with the imine compound or the iminium cation compound and is represented by the formula (3),

where in the formulas, R1, R2, and R3 are each independently a hydrogen atom, an aryl group, an aroyl group, a hetero-ring group, an alkyl group, an alkenyl group, or an alkynyl group, provided that R1 and R2 are not simultaneously hydrogen atoms; R4 and R5 are each independently a hydrogen atom, an alkyl group, an alkenyl group, or an alkynyl group; and R4 and R5 may be bonded together to form a ring.

9 . The method of producing an optically active β-aminocarbonyl compound according to claim 8 , wherein in the column reactor, the amine compound of the formula (1) reacts with the aldehyde compound of the formula (2) to produce an imine compound or an iminium cation compound, and the carbonyl compound of the formula (3) is enolized and reacts with the imine compound or the iminium cation compound in the presence of the asymmetric catalyst particles, to thereby obtain the optically active β-aminocarbonyl compound.

10 . The method of producing an optically active β-aminocarbonyl compound according to claim 1 , wherein the amine compound of the formula (1) is p-anisidine, the aldehyde compound of the formula (2) is dimethoxyacetaldehyde, and the carbonyl compound having an α-hydrogen of the formula (3) is cyclohexanone.

11 . The method of producing an optically active β-aminocarbonyl compound according to claim 10 , wherein the optically active β-aminocarbonyl compound is (1′S,2S),2-(2′,2′-dimethoxy-1′-(4″-methoxyphenylamino)ethyl)cyclohexanone.

12 . The method of producing an optically active β-aminocarbonyl compound according to claim 1 , wherein the optically active β-aminocarbonyl compound converted from the compounds for a Mannich-type reaction is further subjected to optical resolution in the column reactor.

13 . A method of producing an optically active β-aminocarbonyl compound by an asymmetric Mannich-type reaction using a column reactor in which a column is charged with asymmetric catalyst particles, wherein
the asymmetric catalyst particles are resin particles that are prepared from a monomer composition containing 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 as a monomer having an asymmetric source, and a radical polymerization initiator, and act as a catalyst for the asymmetric Mannich-type reaction, and
the method comprises introducing compounds for a Mannich-type reaction into the column reactor to bring the compounds into contact with the asymmetric catalyst particles, to thereby convert the compounds for a Mannich-type reaction to an optically active β-ami

Assignees

• Dexerials Corp

Inventors

• Kanaya Hiroki

Classifications

• C07C2601/18

  with a ring being at least seven-membered · CPC title

• C07B2200/07

  Optical isomers · CPC title

• C07C2601/14

  The ring being saturated · CPC title

• C07C221/00 Primary

  Preparation of compounds containing amino groups and doubly-bound oxygen atoms bound to the same carbon skeleton · CPC title

• B01J2208/06

  Details of tube reactors containing solid particles · CPC title