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WO2010056058A2 - Procédé de préparation d'un dérivé de binaphtol-aldéhyde et son intermédiaire - Google Patents

Procédé de préparation d'un dérivé de binaphtol-aldéhyde et son intermédiaire Download PDF

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Publication number
WO2010056058A2
WO2010056058A2 PCT/KR2009/006675 KR2009006675W WO2010056058A2 WO 2010056058 A2 WO2010056058 A2 WO 2010056058A2 KR 2009006675 W KR2009006675 W KR 2009006675W WO 2010056058 A2 WO2010056058 A2 WO 2010056058A2
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Prior art keywords
formula
compound
halogen
aryl
amino
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PCT/KR2009/006675
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English (en)
Korean (ko)
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WO2010056058A3 (fr
Inventor
김관묵
안윤수
박현정
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AMINOLUX Inc
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AMINOLUX Inc
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Publication of WO2010056058A3 publication Critical patent/WO2010056058A3/fr
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
    • C07C45/27—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by oxidation
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C39/00—Compounds having at least one hydroxy or O-metal group bound to a carbon atom of a six-membered aromatic ring
    • C07C39/12—Compounds having at least one hydroxy or O-metal group bound to a carbon atom of a six-membered aromatic ring polycyclic with no unsaturation outside the aromatic rings
    • C07C39/14—Compounds having at least one hydroxy or O-metal group bound to a carbon atom of a six-membered aromatic ring polycyclic with no unsaturation outside the aromatic rings with at least one hydroxy group on a condensed ring system containing two rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C49/00—Ketones; Ketenes; Dimeric ketenes; Ketonic chelates
    • C07C49/76—Ketones containing a keto group bound to a six-membered aromatic ring
    • C07C49/82—Ketones containing a keto group bound to a six-membered aromatic ring containing hydroxy groups
    • C07C49/825—Ketones containing a keto group bound to a six-membered aromatic ring containing hydroxy groups all hydroxy groups bound to the ring
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C69/00—Esters of carboxylic acids; Esters of carbonic or haloformic acids
    • C07C69/76—Esters of carboxylic acids having a carboxyl group bound to a carbon atom of a six-membered aromatic ring
    • C07C69/94—Esters of carboxylic acids having a carboxyl group bound to a carbon atom of a six-membered aromatic ring of polycyclic hydroxy carboxylic acids, the hydroxy groups and the carboxyl groups of which are bound to carbon atoms of six-membered aromatic rings

Definitions

  • the present invention relates to a process for preparing binaphthol aldehyde derivatives and intermediates thereof which is useful for optical resolution of amino acids or amino alcohols and optical transformation of D and L-forms of amino acids.
  • Optically pure amino acids and amino alcohols are of great industrial importance because they are widely used as ligands for asymmetric catalysts or as starting materials or intermediates for the synthesis of various pharmaceuticals and bioactive substances.
  • the binaphthol derivative is a PLP compound (a) Shaw, JP; Petsko, GA Ringe, D. Biochemistry, 1997, 36, 1329-1342; (b) Walsh, CTJ, which plays a central role in the activity of an enzyme called amino acid lasmaze. Biol. Chem. 1989, 264, 2393-2396).
  • the binaphthol derivatives can be very useful for separating amino alcohols or amino acids into their respective optical isomers, or for preparing optically pure amino acids that have been difficult to prepare by other methods.
  • a known method for producing the binaphthol derivative is to introduce a formyl group (-CHO) using (b) an optically pure binaphthol as a starting material, followed by (ii) a R 3 benzyl group.
  • R is located at the hydrogen position of the 2'hydroxy group of 2,2'-binaphthol-3-aldehyde in which a formyl group is introduced into binaptol. 3 Is substituted
  • the process of introducing benzyl groups is carried out with 2,2'-binaphtol-3-aldehyde. By reacting (Z: halogen) directly.
  • Z halogen
  • the selectivity of 2,2'-binapht-3-aldehyde to 2'hydroxy group is low, resulting in a problem that a product in which a substituent of 2 hydroxy group to hydrogen and a substituent to 2 'hydroxy group is mixed is obtained. . Therefore, there is a need for a technique of increasing the selectivity to hydrogen of the 2 ′ hydroxyl group so that no by-products are generated.
  • the present invention is to solve the above problems of the prior art, to provide a method for producing a binaphthol aldehyde derivative and the intermediate thereof of the formula (8) by a safe method without using a dangerous substance such as n-butyllithium
  • a dangerous substance such as n-butyllithium
  • 2,2'-binaphthol-3-aldehyde (2,2'-binaphthol-3-aldehyde) increases the selectivity to the hydrogen position of the 2 'hydroxy group of the binaphthol aldehyde derivative of formula (8) with high efficiency without generating by-products It is an object to provide a method for producing a.
  • the present invention provides a method for preparing the compound of formula 1, comprising the step of reducing the compound of formula 3 to obtain a compound of formula 2 and oxidizing the compound of formula 2 obtained in the step.
  • each X is independently hydrogen; halogen; Amino; Nitro; Cyano; Formyl; Carboxyl; C1-C10 alkyl unsubstituted or substituted with one or more substituents selected from the group consisting of halogen, hydroxy, amino, cyano, nitro, and C6-C10 aryl; C1-C10 alkylcarbonyl; Aryl of C6 ⁇ C10; And C 1 -C 10 alkoxy;
  • Each Y is independently hydrogen; halogen; Amino; Nitro; Cyano; Formyl; Carboxyl; C1-C10 alkyl unsubstituted or substituted with one or more substituents selected from the group consisting of halogen, hydroxy, amino, cyano, nitro, and C6-C10 aryl; C1-C10 alkylcarbonyl; Aryl of C6 ⁇ C10; And C 1 -C 10 alkoxy; N and m are integers of
  • It provides a method for preparing a compound of Formula 8 including the step of hydrolyzing the compound of Formula 7 obtained in the above step.
  • X is each independently hydrogen; halogen; Amino; Nitro; Cyano; Formyl; Carboxyl; C1-C10 alkyl unsubstituted or substituted with one or more substituents selected from the group consisting of halogen, hydroxy, amino, cyano, nitro, and C6-C10 aryl; C1-C10 alkylcarbonyl; Aryl of C6 ⁇ C10; And C 1 -C 10 alkoxy; Each Y is independently hydrogen; halogen; Amino; Nitro; Cyano; Formyl; Carboxyl; C1-C10 alkyl unsubstituted or substituted with one or more substituents selected from the group consisting of halogen, hydroxy, amino, cyano, nitro, and C6-C10 aryl; C1-C10 alkylcarbonyl; Aryl of C6 ⁇ C10; And C 1 -C 10 alkoxy; N and m
  • the manufacturing method of the present invention unlike the conventional technology, since it does not use a dangerous substance such as n-butyllithium, it is possible to safely manufacture the binaphthol aldehyde derivative of Formula 8 and its intermediate.
  • the present invention relates to a method for preparing the compound of formula 1, comprising the step of reducing the compound of formula 3 to obtain a compound of formula 2 and oxidizing the compound of formula 2 obtained in the step.
  • each X is independently hydrogen; halogen; Amino; Nitro; Cyano; Formyl; Carboxyl; C1-C10 alkyl unsubstituted or substituted with one or more substituents selected from the group consisting of halogen, hydroxy, amino, cyano, nitro, and C6-C10 aryl; C1-C10 alkylcarbonyl; Aryl of C6 ⁇ C10; And C 1 -C 10 alkoxy;
  • Each Y is independently hydrogen; halogen; Amino; Nitro; Cyano; Formyl; Carboxyl; C1-C10 alkyl unsubstituted or substituted with one or more substituents selected from the group consisting of halogen, hydroxy, amino, cyano, nitro, and C6-C10 aryl; C1-C10 alkylcarbonyl; Aryl of C6 ⁇ C10; And C 1 -C 10 alkoxy; N and m are integers of
  • n and m are 0; More preferably, R1 is methyl.
  • the reaction a refers to a reaction proceeding by dissolving a reducing agent (eg, LiAlH 4 , NaBH 4 ) in a solvent (eg, THF), and then adding the compound of Formula 3 above.
  • a reducing agent eg, LiAlH 4 , NaBH 4
  • a solvent eg, THF
  • the reaction is preferably performed for about 3 to 7 hours.
  • the reaction b means dissolving the compound of Formula 2 and an oxidizing agent (for example, pyridinium chlorochromate (PCC), DMSO / Ac 2 O) in a solvent (for example, methylene chloride), and then reacting for about 1 to 6 hours. do.
  • an oxidizing agent for example, pyridinium chlorochromate (PCC), DMSO / Ac 2 O
  • a solvent for example, methylene chloride
  • the compound represented by Chemical Formula 3 may be prepared by a method of reacting the compound represented by Chemical Formula 4 with the compound represented by Chemical Formula 5 using CuCl (OH) -TMEDA (Tetramethylethylenediamine).
  • each X is independently hydrogen; halogen; Amino; Nitro; Cyano; Formyl; Carboxyl; C1-C10 alkyl unsubstituted or substituted with one or more substituents selected from the group consisting of halogen, hydroxy, amino, cyano, nitro, and C6-C10 aryl; C1-C10 alkylcarbonyl; Aryl of C6 ⁇ C10; And C 1 -C 10 alkoxy;
  • Each Y is independently hydrogen; halogen; Amino; Nitro; Cyano; Formyl; Carboxyl; C1-C10 alkyl unsubstituted or substituted with one or more substituents selected from the group consisting of halogen, hydroxy, amino, cyano, nitro, and C6-C10 aryl; C1-C10 alkylcarbonyl; Aryl of C6 ⁇ C10; And C 1 -C 10 alkoxy; N and m are integers of
  • the reaction is carried out using known methods (Hovorka, M .; Sci gel, R .; gunterova, J .; Tichy, M .; Zavada, J. Tetrahedron 1992, 48, 9503) using very inexpensive compounds of formulas (4) and (5). -9516). Briefly, the reaction is characterized in that the compound of formula 4 is dissolved in THF, and then the compound of formula 5 is added, followed by addition of CuCl (OH) -TMED to the mixed solution and reacted under oxygen. See Example 1).
  • Compounds represented by Formulas 4 and 5 are inexpensive and can be purchased in large quantities, unlike expensive binapitol used in the prior art, thereby economically preparing the compound of Formula 1, which is the target compound of the present invention.
  • the compound of Chemical Formula 3 is hydrolyzed to obtain 2,2'-dihydroxy-3-binaphthoic acid, which is obtained by cinchonidine. It may further comprise the step of preparing in an optically pure form by resolution ().
  • the compound of Chemical Formula 3 is hydrolyzed to make a 2,2'-dihydroxy-3-binaphtholic acid (2,2'-dihydroxy-3-binaphtholic acid) derivative to be resolved.
  • Such separation techniques are described by Hovorka, M. et al. (Hovorka, M .; Stibor, I; Holakovsky, R .; Smiskova, I .; Struzka, Vr Czech Rep. (2001), CZ 287879 B6 20010314 Patent written in Czech.Application: CZ 96-64 19960109).
  • the isolated (S) -2,2'-dihydroxy-3-binaphtholic acid derivatives are simply converted into R1 esters by esterification and thus form (S). Pure compound of 4 can be obtained.
  • R separate
  • It relates to a method for preparing the compound of formula 8 comprising the step of hydrolyzing the compound of formula 7 obtained in the above step.
  • X is each independently hydrogen; halogen; Amino; Nitro; Cyano; Formyl; Carboxyl; C1-C10 alkyl unsubstituted or substituted with one or more substituents selected from the group consisting of halogen, hydroxy, amino, cyano, nitro, and C6-C10 aryl; C1-C10 alkylcarbonyl; Aryl of C6 ⁇ C10; And C 1 -C 10 alkoxy; Each Y is independently hydrogen; halogen; Amino; Nitro; Cyano; Formyl; Carboxyl; C1-C10 alkyl unsubstituted or substituted with one or more substituents selected from the group consisting of halogen, hydroxy, amino, cyano, nitro, and C6-C10 aryl; C1-C10 alkylcarbonyl; Aryl of C6 ⁇ C10; And C 1 -C 10 alkoxy; N and m
  • halogen examples include Br, Cl, I and the like.
  • the above-described information may be applied to the process up to the preparation of the compound of Formula 1.
  • N, N-dimethylformamide N, N-dimethylformamide, DMF
  • THF tetrahydrofuran
  • CH 2 Cl 2 tetrahydrofuran
  • Examples of the base used in the reaction a include organic or inorganic bases such as Et 3 N, NaH, NaOH, and NEt 3 or NaH.
  • the reaction a is made at 0 ⁇ 30 °C, preferably carried out at room temperature.
  • reaction a Is mainly substituted at the hydrogen position of 2 hydroxy
  • Some compounds are produced in which both are substituted at the hydrogen positions of the 2 hydroxy group and the 2 'hydroxy group.
  • reaction by-products can be recycled by hydrolysis to form the compound of Formula 1 again.
  • the compound of Chemical Formula 6 may be obtained by recrystallization with a purity of 98% or more and a yield of 90% or more.
  • the compound of Formula 1 in the presence of a base Reaction with (Z: halogen) gives a compound of the formula (7).
  • N, N-dimethylformamide (N, N-dimethylformamide, DMF), tetrahydrofuran (THF), CH 2 Cl 2, etc. may be used as a solvent for the reaction in the reaction b, and DMF is preferable.
  • the base used in the reaction b include organic or inorganic bases such as Et 3 N, NaH, NaOH, and NEt 3 or NaH.
  • the obtained compound of formula 7 is hydrolyzed in a conventional manner to obtain a compound of formula 8.
  • the yield is at least 90%.
  • Compound 3 was synthesized according to the synthesis method of the known paper (Hovorka, M .; Sci gel, R .; gunterova, J .; Tichy, M .; Zavada, J. Tetrahedron 1992, 48, 9503-9516). That is, 3-hydroxy-2-naphthalate methyl ester (2.0 g, 9.89 mmol) was dissolved in THF (20 ml), followed by 2-naphthol (1.42 g, 9.89 mmol). Added. CuCl (OH) -TMEDA (1.15 g, 4.94 mmol) was added to this mixed solution at room temperature and stirred for 3 days under oxygen.
  • Lithium aluminum hydride (LiAlH 4 , 0.51 g, 13.3 mmol) was dissolved in THF (30 ml), and then 2,2'-dihydroxy-1,1'-binafphyl-3 prepared in Example 1 was used.
  • -Carboxylic acid methyl ester (3.07 g, 8.89 mmol) was added in an ice bath. After stirring for 5 hours at room temperature, the precipitate was filtered off and the resulting solution was evaporated to give a 2,2, -dihydroxy-3-hydroxymethyl-1,1'-binaphthalene compound (2.53 g, yield: 90%).

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

Abstract

La présente invention concerne un procédé de préparation d'un composé représenté par la formule chimique 1 suivante et un procédé identique de préparation d'un dérivé de binaphtol-aldéhyde. Le procédé de préparation d'un composé représenté par la formule chimique 1 suivante comprend les étapes consistant à : réduire un composé représenté par la formule chimique 3 suivante pour obtenir un composé représenté par la formule chimique 2 suivante ; et oxyder le composé représenté par la formule chimique 2 suivante obtenu à l'étape précédente.
PCT/KR2009/006675 2008-11-14 2009-11-13 Procédé de préparation d'un dérivé de binaphtol-aldéhyde et son intermédiaire Ceased WO2010056058A2 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
KR1020080113616A KR101087500B1 (ko) 2008-11-14 2008-11-14 바이나프톨 알데히드 유도체 및 그의 중간체의 제조방법
KR10-2008-0113616 2008-11-14

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WO2010056058A2 true WO2010056058A2 (fr) 2010-05-20
WO2010056058A3 WO2010056058A3 (fr) 2010-08-19

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KR101270586B1 (ko) 2010-11-26 2013-06-03 주식회사 아미노로직스 광학적으로 순수한 2,2'-디히드록시-1,1'-바이나프틸-3-카르복실산의 제조방법

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KR100661280B1 (ko) * 2005-02-01 2006-12-26 이화여자대학교 산학협력단 바이나프톨 유도체, 및 광학적 분할 또는 광학적 변환을위한 그의 용도

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KR101087500B1 (ko) 2011-11-28
KR20100054628A (ko) 2010-05-25

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