Method for producing optically active compound having binaphthol moiety and intermediate composition for suppressing deprotection

Abstract

To provide a method for efficiently producing an optically active compound.SOLUTION: There is provided a production method including the steps of: adding a nitrogen-containing basic compound with a pKa of 4 to 10 to prepare an intermediate composition at the end of the reaction to synthesize general formula (III) by reacting general formula (II) with a protecting group introducing agent; reacting the intermediate composition with general formula (IV) to obtain general formula (V); deprotecting (V) to obtain the general formula (VI); and reacting (VI) with a binaphthol which may have substituents. HOOC-A1-OH(II), PG-OOC-A1-OH(III), HOOC-A2-R1(IV), PG-OOC-A1-OOC-A2-R1(V), HOOC-A1-OOC-A2-R1(VI)SELECTED DRAWING: None

Description

[Technical field]

[0001] The present disclosure relates to a method for producing an optically active compound having a binaphthol moiety with a specific structure, and to an intermediate composition for inhibiting deprotection used in the production method. [Background technology]

[0002] In recent years, polymerizable liquid crystal compounds have been used in optically anisotropic films such as polarizing plates, polarizing reflectors, and retardation plates. This is because polymerizable liquid crystal compounds exhibit optical anisotropy in the liquid crystal state, and this anisotropy is fixed by polymerization. Since the optical properties required for optically anisotropic films differ depending on the purpose, various compounds are sometimes combined and used as polymerizable liquid crystal compositions to obtain properties suited to the purpose.

[0003] The addition of an optically active compound to a polymerizable liquid crystal composition induces a helical structure. By controlling the type and amount of the optically active compound, the helical pitch of the optically anisotropic film with twisted orientation can be changed, enabling various applications. The structure of an optically active compound having a binaphthol moiety containing a polymerizable group is disclosed in, for example, Patent Document 1, and a manufacturing method is also outlined. However, the manufacturing method described in Patent Document 1 is likely to produce a large amount of by-products, and purification is performed by column chromatography, which is not suitable for industrialization. There has been a demand for a manufacturing method that can efficiently produce optically active compounds having a binaphthol moiety with a specific structure containing a polymerizable group with few by-products and in high yield. [Prior art documents] [Patent documents]

[0004] [Patent Document 1] JP 2005-263778 A Summary of the Invention [Problem to be solved by the invention]

[0005] In view of the above-mentioned circumstances, an object of the present disclosure is to provide a production method capable of efficiently producing an optically active compound having a binaphthol moiety having a specific structure containing a polymerizable group with little by-products and in high yield. [Means for solving the problem]

[0006] The present disclosure includes the following aspects. [1] The following general formula (I)

[0007] [ka] (In the general formula (I), A 1 each independently represents a 4,4'-biphenylene group, a 1,4-phenylene group, a 1,4-cyclohexylene group, or a naphthalene-2,6-diyl group; A 2 each independently represents a 4,4'-biphenylene group, a 1,4-phenylene group, a 1,4-cyclohexylene group, or a naphthalene-2,6-diyl group; A 1 and A 2 each independently may have a substituent E, R 1 each independently represents a group selected from general formula (R-1), General formula (R-1): -L r1 -R sp1 -Z 1 In general formula (R-1), L r1 represents -O-, -S-, -COO-, -OCO-, -OCOO-, or a single bond; R sp1 represents an alkylene group having 1 to 20 carbon atoms in which one -CH2- or two or more non-adjacent -CH2- may each be independently replaced by -O-, -COO-, or -OCO-, or a single bond; Z 1 represents a polymerizable functional group. Substituents E, E 1 and E 2each independently represents an alkyl group having 1 to 3 carbon atoms or a halogen, and m1 and m2 each independently represent an integer of 0 to 2. A method for producing an optically active compound having a binaphthol moiety represented by the following formula: The following general formula (II)

[0008] [ka] (In the formula, A 1 has the same meaning as above.) and a carboxylic acid protecting group introducing agent to obtain a compound represented by the following general formula (III):

[0009] [ka] (In the formula, PG represents a protecting group, A 1 has the same meaning as above.) Upon completion of a protecting group introduction reaction for synthesizing a compound represented by the general formula (III), a nitrogen-containing basic compound having a pKa of 4 to 10 is added to prepare an intermediate composition for suppressing deprotection, which contains the compound represented by the general formula (III) and a nitrogen-containing basic compound having a pKa of 4 to 10; The deprotection inhibiting intermediate composition is added to the compound represented by the following general formula (IV):

[0010] [ka] (In the formula, A 2 , and R 1 Each has the same meaning as above.) and reacting the compound represented by the following general formula (V):

[0011] [ka] (Wherein, PG, A 1 , A 2 , and R 1 Each has the same meaning as above.) and obtaining a compound represented by the formula: By deprotecting the protecting group in the compound represented by the general formula (V), a compound represented by the following general formula (VI) can be obtained:

[0012] [ka] (In the formula, A 1 , A 2 , and R 1 Each has the same meaning as above.) and obtaining a compound represented by the formula: A compound represented by the general formula (VI) and a substituent E 1 and E 2 with a binaphthol which may have at least one of the following: The present invention relates to a method for producing an optically active compound having a binaphthol moiety represented by the general formula (I).

[0013] [2] The method for producing an optically active compound having a binaphthol moiety according to [1] above, wherein the nitrogen-containing basic compound is at least one selected from the group consisting of 4-dimethylaminopyridine, morpholine, pyridine, 1-naphthylamine, 4,4'-diaminodiphenyl ether, N-methylimidazole, tributylamine, N,N-dimethylaniline, N,N-diethylaniline and aniline. [3] The method for producing an optically active compound having a binaphthol moiety according to [1] or [2] above, wherein the nitrogen-containing basic compound is used in an amount of 0.1 mol to 1.5 mol per 1 mol of the compound represented by general formula (III). [4] The method for producing an optically active compound having a binaphthol moiety according to any one of the above [1] to [3], wherein the protecting group in the compound represented by the above general formula (III) is at least one selected from the group consisting of an ethoxymethyl group, a methoxymethyl group, a methoxyethoxymethyl group, a benzyloxymethyl group, a tetrahydropyranyl group, a 2,2,2-trichloroethyl group, an alkyl group having 1 to 4 carbon atoms, a benzyl group, and a triphenylmethyl group. [5] The following general formula (III)

[0014] [ka] (In the formula, PG represents a protecting group, A 1 has the same meaning as above.) and a nitrogen-containing basic compound having a pKa of 4 to 10. [6] The deprotection suppressing intermediate composition according to [5], wherein the nitrogen-containing basic compound is at least one selected from the group consisting of 4-dimethylaminopyridine, morpholine, pyridine, 1-naphthylamine, 4,4'-diaminodiphenyl ether, N-methylimidazole, tributylamine, N,N-dimethylaniline, N,N-diethylaniline, and aniline. [7] The intermediate composition for suppressing deprotection according to [5] or [6], containing the nitrogen-containing basic compound in an amount of 0.1 mol to 1.5 mol per 1 mol of the compound represented by general formula (III). [8] The intermediate composition for suppressing deprotection according to any one of the items [5] to [7], wherein the protecting group in the compound represented by the general formula (III) is at least one selected from the group consisting of an ethoxymethyl group, a methoxymethyl group, a methoxyethoxymethyl group, a benzyloxymethyl group, a tetrahydropyranyl group, a 2,2,2-trichloroethyl group, an alkyl group having 1 to 4 carbon atoms, a benzyl group, and a triphenylmethyl group. Effect of the Invention

[0015] According to an embodiment of the present disclosure, it is possible to provide a production method that can efficiently produce an optically active compound having a binaphthol moiety with a specific structure containing a polymerizable group with little by-products and in high yield. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0016] Hereinafter, embodiments and examples of the present disclosure will be described with reference to chemical formulas, etc. However, the present disclosure can be implemented in many different forms, and should not be construed as being limited to the description of the embodiments and examples exemplified below. In the present disclosure, (meth)acrylic refers to either acrylic or methacrylic, (meth)acrylate refers to either acrylate or methacrylate, and (meth)acryloyl refers to either acryloyl or methacryloyl. In addition, in this specification, the use of "to" indicating a numerical range is used to mean that the numerical values ​​before and after it are included as the lower limit and upper limit.

[0017] The method for producing an optically active compound having a binaphthol moiety represented by the following general formula (I) of the present disclosure includes the steps of: A step 1 of reacting a compound represented by the following general formula (II) with a carboxylic acid protecting group introducing agent to synthesize a compound represented by the following general formula (III) and adding a nitrogen-containing basic compound having a pKa of 4 to 10 at the end of the protecting group introduction reaction to prepare an intermediate composition for suppressing deprotection, which contains the compound represented by the general formula (III) and the nitrogen-containing basic compound having a pKa of 4 to 10; Step 2 of adding a compound represented by the following general formula (IV) to the intermediate composition and reacting to obtain a compound represented by the following general formula (V); Step 3 of obtaining a compound represented by the following general formula (VI) by deprotecting the protecting group in the compound represented by the general formula (V); A compound represented by the general formula (VI) and a substituent E 1 and E 2 Step 4 of reacting a binaphthol having at least one of the following formula (1) and (2); The manufacturing method includes the steps of:

[0018] [ka] (In the formula, A 1each independently represents a 4,4'-biphenylene group, a 1,4-phenylene group, a 1,4-cyclohexylene group, or a naphthalene-2,6-diyl group; A 2 each independently represents a 4,4'-biphenylene group, a 1,4-phenylene group, a 1,4-cyclohexylene group, or a naphthalene-2,6-diyl group; A 1 and A 2 each independently may have a substituent E, R 1 each independently represents a group selected from general formula (R-1), General formula (R-1): -L r1 -R sp1 -Z 1 In general formula (R-1), L r1 represents -O-, -S-, -COO-, -OCO-, -OCOO-, or a single bond; R sp1 represents an alkylene group having 1 to 20 carbon atoms in which one -CH2- or two or more non-adjacent -CH2- may each be independently replaced by -O-, -COO-, or -OCO-, or a single bond; Z 1 represents a polymerizable functional group. Substituents E, E 1 and E 2 each independently represents an alkyl group having 1 to 3 carbon atoms or a halogen; m1 and m2 each independently represent 0 to 2. PG represents a protecting group.

[0019] According to the method for producing an optically active compound having a binaphthol moiety of the present disclosure, an optically active compound having a binaphthol moiety can be produced efficiently in high yield with few by-products, while having a specific side chain represented by general formula (I) which contains at least two ester bonds and a polymerizable group at its terminal. As a method for producing an optically active compound having a binaphthol moiety with a specific side chain represented by the general formula (I) containing at least two ester bonds and a polymerizable group at the end, there is a method for sequentially synthesizing the side chain portions by reacting the binaphthol moiety with a compound having a carboxy group and a hydroxyl group to form a first ester bond, and then reacting the carboxy group with a compound having a polymerizable group at the end to form a second ester bond. However, in the case of this method, when synthesizing an optically active compound having (R)-naphthol and an optically active compound having (S)-naphthol, which is an enantiomer, it is necessary to synthesize the side chain portions separately, which increases the number of synthesis steps and reduces productivity. On the other hand, a method of producing the compound by synthesizing the entire side chain portion having a carboxy group at one end in advance and reacting the side chain portion having a carboxy group at one end with the binaphthol moiety to form an ester bond is desirable from the viewpoint of productivity, since an optically active compound having an (R)-naphthol body and an optically active compound having an (S)-naphthol body can be synthesized by synthesizing a common side chain and condensing it. Also, a method of synthesizing the entire side chain portion having a carboxy group at one end in advance and reacting it with the binaphthol moiety is desirable from the viewpoint of productivity, compared with a method of synthesizing the entire side chain portion having a carboxylic acid chloride at the end in advance and reacting it with the binaphthol moiety. This is because a side chain having a carboxy group has high storage stability and can be easily synthesized since there is no step of preparing an acid chloride. As per the original application, HOOC-A 1 -OOC-A 2 -R 1 When synthesizing a side chain containing an ester bond such as HOOC-A, 1 -OH and HOOC-A 2 -R 1 and HOOC-A are condensed. 1 In order to prevent the condensation reaction of -OH with each other and the production of a large amount of impurities, HOOC-A 1 A protecting group was introduced to the carboxyl group of -OH to give PG-OOC-A 1 -OH, then HOOC-A 2 -R 1However, it is preferable to carry out a condensation reaction with PG-OOC-A 1 It was found that -OH is a problem in that it is easy to generate impurities due to the acidity of the hydroxyl group, and the protecting group is removed and side reactions proceed. 1 Not only does this reduce the yield of --OH, but it also requires tedious purification by column chromatography. In contrast, in this disclosure, 1 After the -OH protecting group introduction reaction is completed, a nitrogen-containing basic compound with a pKa of 4 to 10 is added to PG-OOC-A 1 The method further comprises the step of preparing an intermediate composition for inhibiting deprotection, the intermediate composition comprising -OH and a nitrogen-containing basic compound having a pKa of 4 to 10. 1 At the end of the -OH protecting group introduction reaction, a nitrogen-containing basic compound with a pKa of 4 to 10 was added to produce PG-OOC-A. 1 This can suppress the elimination of the -OH protecting group and the generation of impurities due to the progression of side reactions. 1 Not only does this improve the yield of -OH, it also eliminates the need for cumbersome purification by column chromatography, and it also makes it possible to synthesize in advance the entire side chain portion having a carboxy group at one end in one pot (within the same reaction vessel) (the symbols in the formulae above are as defined above).

[0020] In this manner, the production method of the present disclosure can efficiently produce an optically active compound having a binaphthol moiety with a specific structure containing a polymerizable group with little by-product production and in high yield. The production method of the present disclosure is suitable for industrial scale production since it can produce an optically active compound having a binaphthol moiety with a specific structure containing a polymerizable group without requiring column purification, which is a complicated procedure. The optically active compound having a binaphthol moiety with a specific structure including a polymerizable group obtained by the production method of the present disclosure can be obtained with high purity, and therefore it is possible to form a liquid crystal coating film in which inhibition of liquid crystal alignment and a cholesteric liquid crystal coating film in which pitch variation is reduced.

[0021] Hereinafter, the optically active compound having a binaphthol moiety having a specific structure obtained by the production method of the present disclosure will be described, and then each step of the production method of the optically active compound having a binaphthol moiety having a specific structure of the present disclosure will be described.

[0022] 1. Optically active compounds containing a binaphthol moiety In the optically active compound having a binaphthol moiety represented by the general formula (I) produced by the present invention, 1 each independently represents a 4,4'-biphenylene group, a 1,4-phenylene group, a 1,4-cyclohexylene group, or a naphthalene-2,6-diyl group. From the viewpoint of compatibility with the liquid crystal compound to be used in combination, 1 may each independently be a 4,4'-biphenylene group, a 1,4-phenylene group, or a naphthalene-2,6-diyl group, or may be a 4,4'-biphenylene group or a 1,4-phenylene group. In the general formula (I), A 2 each independently represents a 4,4'-biphenylene group, a 1,4-phenylene group, a 1,4-cyclohexylene group, or a naphthalene-2,6-diyl group. From the viewpoint of compatibility with the liquid crystal compound to be used in combination, 2 may each independently be a 4,4'-biphenylene group, a 1,4-phenylene group, or a naphthalene-2,6-diyl group, or may be a 4,4'-biphenylene group or a 1,4-phenylene group. A 1 and A 2 In the formula, 1,4-cyclohexylene is L 1 , L 2 Or L r1 There may be stereoisomers of cis and trans configurations based on the difference in the configuration of the carbon atom bonded to 1,4-cyclohexylene. 1,4-cyclohexylene may be either cis or trans, or may be a mixture of cis and trans isomers, but because of good orientation, it is preferably trans or cis, and more preferably trans.

[0023] A 1 and A 2 may each independently have a substituent E, that is, an alkyl group having 1 to 3 carbon atoms, or a halogen. The alkyl group having 1 to 3 carbon atoms may be either linear or branched, and examples thereof include a methyl group, an ethyl group, an n-propyl group, and an i-propyl group. The halogen may be fluorine, chlorine, bromine or iodine, preferably fluorine, chlorine or bromine.

[0024] In the general formula (I), R 1 each independently represents a group selected from the general formula (R-1). General formula (R-1): -L r1 -R sp1 -Z 1 In general formula (R-1), L r1 represents -O-, -S-, -COO-, -OCO-, -OCOO-, or a single bond; R sp1 represents an alkylene group having 1 to 20 carbon atoms in which one -CH2- or two or more non-adjacent -CH2- may each be independently replaced by -O-, -COO-, or -OCO-, or a single bond; Z 1 represents a polymerizable functional group.

[0025] In general formula (R-1), L r1 represents -O-, -S-, -COO-, -OCO-, -OCOO-, or a single bond; however, from the viewpoint of availability of raw materials and ease of synthesis, it is preferable that each independently represent -O-, -COO-, -OCO-, -OCOO-, or a single bond, and when a plurality of these are present, they may be the same or different.

[0026] In general formula (R-1), R sp1Specifically, from the viewpoint of availability of raw materials and ease of synthesis, it is more preferable that each independently represent an alkylene group having 1 to 12 carbon atoms which may be replaced by one -CH2- or two or more non-adjacent -CH2-, each independently represent an alkylene group having 1 to 12 carbon atoms or a single bond, further more preferably each independently represent an alkylene group having 2 to 10 carbon atoms, and particularly preferably each independently represent an alkylene group having 2 to 6 carbon atoms, and when there are a plurality of -CH2-, they may be the same or different.

[0027] In general formula (R-1), Z 1 represents a polymerizable functional group. The polymerizable functional group used in the present disclosure can be any group used in conventional polymerizable liquid crystal compounds without any restrictions. Examples of the polymerizable functional group include cyclic ether-containing groups such as oxirane rings and oxetane rings, and ethylenic double bond-containing groups. Among them, ethylenic double bond-containing groups are preferred because they exhibit photocurability and are easy to handle. Z 1 The polymerizable functional groups in each of the formulas (Z-1) to (Z-7) are preferably independently selected from the following formulas (Z-1) to (Z-7). In the following formulas (Z-1) to (Z-7), * (asterisk) represents R sp1 The bond position is shown.

[0028] [ka] (In formulas (Z-1) to (Z-7), R z are each independently a hydrogen atom, a fluorine atom, a chlorine atom, a bromine atom, an iodine atom, a methyl group, an ethyl group, or a trifluoromethyl group.

[0029] When using ultraviolet polymerization as the polymerization method, Z 1is preferably the formula (Z-1), the formula (Z-2), the formula (Z-3), the formula (Z-5), or the formula (Z-7), more preferably the formula (Z-1), the formula (Z-3), or the formula (Z-7), further preferably the formula (Z-1). In the formula (Z-1), R z It is more preferable that is a hydrogen atom, a methyl group or a trifluoromethyl group.

[0030] In the general formula (I), the binaphthalene ring may have a substituent E 1 and E 2 each independently represents an alkyl group having 1 to 3 carbon atoms or a halogen; m1 and m2 each independently represent 0 to 2. Substituent E 1 and E 2 Examples of the alkyl group having 1 to 3 carbon atoms or the halogen in the above include the same as those exemplified for the substituent E. m1 and m2 each independently represent 0 to 2, and may be 0 or 1.

[0031] The optically active compound having a binaphthol moiety represented by general formula (I) produced in the present disclosure is a chiral polymerizable binaphthol derivative. 1 -OOC-A 2 -L r1 -R sp1 -Z 1 Specific examples of the compound include the optically active compounds having a binaphthol moiety with a side chain shown in Ch-1 to Ch-48 in the following table, but are not limited thereto. In addition, in the following Ch-1 to Ch-48, R sp1 -(CH2) n The n in - represents an integer of 1 to 20, but may be an integer of 2 or more, an integer of 12 or less, an integer of 10 or less, or an integer of 6 or less. In addition, in the following Ch-1 to Ch-48, Z 1 R in formula (Z-1) zis preferably a hydrogen atom or a methyl group, and more preferably a hydrogen atom. In addition, in the optically active compounds having a binaphthol moiety with a side chain shown in Ch-1 to Ch-48 in the following table, 1 , and A 2 At least one of the substituents E, E 1 and E 2 It may have at least one of the following.

[0032] [Table 1]

[0033] 2. Each step of the manufacturing process In the following explanation, each symbol in the general formula, except for PG, is the same as explained in the optically active compound having a binaphthol moiety represented by the general formula (I) above, and therefore explanation here will be omitted. In each step, the A of the compounds represented by general formula (II), general formula (III), general formula (V), and general formula (VI) 1 is the A of the optically active compound having a binaphthol moiety represented by the general formula (I) to be produced. 1 and A of the compounds represented by general formula (IV), general formula (V), and general formula (VI) used 2 and R 1 and A of the optically active compound having a binaphthol moiety represented by the general formula (I) to be produced. 2 and R 1 is the same as: However, in the optically active compound having a binaphthol moiety represented by the general formula (I), the two side chains may be the same or different, and when the two side chains are different, two or more types of the compound represented by the general formula (II) and the compound represented by the general formula (IV) may be used. From the viewpoint of improving the yield, the two side chains in the optically active compound having a binaphthol moiety represented by the general formula (I) may be the same.

[0034] (1) Process 1 In the production method of the present disclosure, the compound represented by the general formula (II) (HOOC-A 1 The compound represented by the general formula (III) (PG-OOC-A-OH) is reacted with a carboxylic acid protecting group introducing agent to obtain a compound represented by the general formula (III) (PG-OOC-A-OH). 1 Upon completion of the protecting group introduction reaction to synthesize the compound represented by the general formula (III) (PG-OOC-A 1 The method includes a step of preparing an intermediate composition for inhibiting deprotection, the intermediate composition comprising a nitrogen-containing basic compound having a pKa of 4 to 10 and a substituted or unsubstituted alkyl group.

[0035] The compound represented by the general formula (II) (HOOC-A 1 -OH, where A 1 A is a 4,4'-biphenylene group, a 1,4-phenylene group, a 1,4-cyclohexylene group, or a naphthalene-2,6-diyl group) and can be selected from commercially available products. 1 When has a substituent E, for example, 3-methyl-1,4-phenylene group, 3-chloro-1,4-phenylene group, etc. can be mentioned, and for example, it is possible to synthesize by referring to Liquid Crystals (2018), 45(4), 634-640, Liquid Crystals (2018), 45(8), 1155-1163, etc.

[0036] Examples of carboxylic acid protecting group introducing agents used in the production method of the present disclosure include chloromethyl ethyl ether, chloromethyl methyl ether, 2-methoxyethoxymethyl chloride, benzyl chloromethyl ether, dichloromethyl methyl ether, 3,4-dihydro-2H-pyran, 2,2,2-trichloroethanol, tert-butyl alcohol, ethanol, methanol, benzyl bromide, and trityl chloride. In view of excellent reaction selectivity during introduction of a protecting group, the carboxylic acid protecting group introducing agent used in the production method of the present disclosure may be at least one selected from the group consisting of chloromethyl ethyl ether and chloromethyl methyl ether.

[0037] In the above-mentioned protecting group introduction reaction, 1 The amounts of the carboxylic acid protecting group introducing agent and the carboxylic acid protecting group introducing agent used are not particularly limited, but may be 0.9 mol to 1.5 mol, or 1.0 mol to 1.1 mol, per 1 mol of the compound represented by the general formula (II).

[0038] The compound represented by the general formula (II) (HOOC-A 1 When reacting the carboxylic acid protecting group-introducing agent with the carboxylic acid protecting group-introducing agent, a base having a pKa of more than 10 may be used in order to improve the reactivity of the protecting group-introducing reaction. Examples of the base having a pKa of more than 10 include N,N-diisopropylethylamine, triethylamine, sodium hydroxide, and potassium hydroxide.

[0039] The compound represented by the general formula (II) (HOOC-A 1 The reaction between the carboxylic acid protecting group-introducing agent and the carboxylic acid protecting group-introducing agent is preferably carried out in an organic solvent. Examples of organic solvents used in the protective group introduction reaction include ketones such as acetone, 2-butanone, methyl isobutyl ketone, and cyclopentanone; cyclic ethers such as tetrahydrofuran (THF), 2-methyltetrahydrofuran, 4-methyltetrahydropyran, tetrahydropyran, 1,3-dioxolane, and 1,4-dioxane; amides such as N-methyl-2-pyrrolidone (NMP), N,N-dimethylformamide (DMF), and N,N-dimethylacetamide (DMAc); sulfur-containing solvents such as dimethyl sulfoxide (DMSO) and sulfolane; and mixed solvents thereof. Among these, from the viewpoint of the influence of the residual solvent in the next step, the organic solvent may be at least one selected from the group consisting of cyclic ethers such as tetrahydrofuran (THF), 2-methyltetrahydrofuran, 4-methyltetrahydropyran, tetrahydropyran, 1,3-dioxolane, and 1,4-dioxane.

[0040] The amount of the organic solvent used is appropriately adjusted depending on the type of each compound to be reacted, and is not particularly limited. 1 The amount of the organic solvent is preferably 10% by mass to 95% by mass, and more preferably 60% by mass to 80% by mass, based on the total amount of the reaction solution used when reacting the carboxylic acid protecting group-introducing agent with the carboxylic acid protecting group-introducing agent.

[0041] In the production method of the present disclosure, the compound represented by the general formula (II) (HOOC-A 1 When reacting the carboxylic acid protecting group-introducing agent with the carboxylic acid protecting group-introducing agent, it is preferable to carry out the reaction under an inert atmosphere such as a nitrogen stream in order to prevent side reactions. In the production method of the present disclosure, the compound represented by the general formula (II) (HOOC-A 1 The reaction temperature when reacting the carboxylic acid protecting group-introducing agent with the carboxylic acid protecting group-introducing agent in the presence of a base having a pKa of more than 10 may be in the range of 1° C. to 30° C., or in the range of 5° C. to 20° C., in order to improve the reaction yield. The reaction time may be appropriately selected depending on the scale, and may be in the range of 10 minutes to 24 hours, or in the range of 30 minutes to 2 hours.

[0042] In the compound represented by the general formula (III) obtained by reacting the compound represented by the general formula (II) with a carboxylic acid protecting group introducing agent, examples of the introduced protecting group (PG) include an ethoxymethyl group, a methoxymethyl group, a methoxyethoxymethyl group, a benzyloxymethyl group, a tetrahydropyranyl group, a 1-chloro-1-methoxymethyl group, a 2,2,2-trichloroethyl group, an alkyl group having 1 to 4 carbon atoms, a benzyl group, and a triphenylmethyl group. 1 represents the A in the compound represented by the general formula (II) used. 1 is the same as:

[0043] In step 1, a nitrogen-containing basic compound having a pKa of 4 to 10 is added at the completion of a protecting group introduction reaction for synthesizing a compound represented by general formula (III) to prepare an intermediate composition for suppressing deprotection, which contains the compound represented by general formula (III) and a nitrogen-containing basic compound having a pKa of 4 to 10. In this step, a nitrogen-containing basic compound having a pKa of 4 to 10 is used as a deprotection inhibitor for suppressing the elimination of a protecting group. If the nitrogen-containing basic compound used has a pKa of 4 or more, it is easy to suppress the elimination of a protecting group, and the pKa may be 5 or more, or may be 6 or more. On the other hand, since cleavage of an ester bond does not occur, the pKa is set to 10 or less, but the pKa may be 9.5 or less, or may be 9.0 or less. In the present invention, pKa refers to a value determined by acid-base titration as described below. In an environment of 25°C, 0.100g of the sample to be measured for pKa is precisely weighed into a 250mL conical beaker, 150mL of tetrahydrofuran / water = 6 / 4 (volume ratio) is added, and the solution is dissolved for 30 minutes to obtain a measurement solution. 10μL of 0.1mol / L potassium hydroxide ethyl alcohol solution (e.g. Fuji Film Wako) is added in increments of 10μL, and titration is performed while reading the pH each time. 0.1mol / L potassium hydroxide ethyl alcohol solution is added until the pH becomes 10 or higher and there is no change in the pH even after adding 30μL. From the results obtained, the pH is plotted against the amount of 0.1mol / L potassium hydroxide ethyl alcohol solution added to obtain a titration curve. The point where the slope of the pH change is greatest from the obtained titration curve is determined as the neutralization point, and the pH at half the amount of 0.1mol / L potassium hydroxide ethyl alcohol solution added required to reach the neutralization point is read from the titration curve, and the pH value read is determined as the pKa.

[0044] In this step, examples of the nitrogen-containing basic compound having a pKa of 4 to 10 include 4-dimethylaminopyridine, morpholine, pyridine, 1-naphthylamine, 4,4'-diaminodiphenyl ether, N-methylimidazole, tributylamine, N,N-dimethylaniline, N,N-diethylaniline, and aniline. In this step, the nitrogen-containing basic compound having a pKa of 4 to 10 used may be at least one selected from the group consisting of 4-dimethylaminopyridine, morpholine, N,N-dimethylaniline, and N,N-diethylaniline, since it is inexpensive and does not easily volatilize from the solution due to its high boiling point.

[0045] The amount of the nitrogen-containing basic compound having a pKa of 4 to 10 may be in the range of 0.1 mol to 2.0 mol, 0.1 mol to 1.0 mol, or 0.1 mol to 0.5 mol, relative to 1 mol of the compound represented by general formula (III).

[0046] In the present invention, the end of the reaction for introducing a protecting group by adding a nitrogen-containing basic compound having a pKa of 4 to 10 is the time when the raw material (HOOC-A) is dissolved in water by HPLC (high performance liquid chromatography). 1 The time period refers to within 120 minutes from the time of sampling (end point of reaction) of the reaction solution at which the peak of the ion exchange group (—OH) is 0.1 Area % or less. Although it takes, for example, 45 minutes to obtain the results of HPLC measurement of the sampled reaction solution, it is preferable to add the nitrogen-containing basic compound having a pKa of 4 to 10 as soon as possible from the end point of the reaction so that the elimination reaction of the protecting group and the side reactions associated therewith do not proceed. The nitrogen-containing basic compound having a pKa of 4 to 10 may be added within 90 minutes from the end point of the reaction, within 60 minutes from the end point of the reaction, or within 45 minutes from the end point of the reaction, within 5 minutes, within 1 minute, or immediately after (within 5 seconds) after the end point of the reaction is confirmed. The HPLC measurement is performed by sampling the reaction solution every 15 minutes after 30 minutes from the start of the reaction, and then performing HPLC measurement on the reaction solution sample. The start of the reaction here refers to the time when the dropwise addition of the base having a pKa of more than 10 is completed after mixing the compound represented by the general formula (II) and the carboxylic acid protecting group introducing agent when a base having a pKa of more than 10 is used in the reaction, and refers to the time when the mixing of the compound represented by the general formula (II) and the carboxylic acid protecting group introducing agent is completed when a base having a pKa of more than 10 is not used in the reaction. The measurement conditions for the HPLC measurement are as follows. HPLC (High Performance Liquid Chromatograph): Shimadzu LC2010CHT Column: YMC-Pack Pro C18 s 4.6 x 250 mm Column temperature: 40℃ Mobile phase A: acetonitrile / water (volume ratio 50:50) Mobile phase B: Acetonitrile / THF (volume ratio 50:50) Concentration gradient of mobile phase A and B (volume ratio): 0 min (A / B = 80 / 20) → 20 min (A / B = 0 / 100) → 25 min (A / B = 0 / 100) → 30 min (A / B = 80 / 20) → 35 min (A / B = 80 / 20) Flow rate: 1.0 mL / min Detection wavelength: 224 nm (UV)

[0047] The thus obtained intermediate composition for suppressing deprotection, which contains the compound represented by the general formula (III) and a nitrogen-containing basic compound having a pKa of 4 to 10, is a composition used for suppressing deprotection of the compound represented by the general formula (III) and improving storage stability. Therefore, the intermediate composition for suppressing deprotection contains the compound represented by the general formula (IV) (HOOC-A) for condensation reaction with the hydroxyl group of the compound represented by the general formula (III). 2 -R 1 ) and a condensing agent. The deprotection inhibiting intermediate composition may be used immediately in the next step, or may be stored before being used in the next step. When the deprotection inhibiting intermediate composition is stored, it is typically stored at 0° C. to 40° C. for up to 72 hours. Since the intermediate composition for inhibiting deprotection can be stored, there is no need to immediately carry out step 2 thereafter, which increases the flexibility of the production schedule and is a great advantage in terms of industrial production.

[0048] (2) Process 2 In the production method of the present disclosure, the deprotection inhibiting intermediate composition obtained in the step 1 is added with a compound represented by general formula (IV) (HOOC-A 2 -R 1 ) is added and reacted to obtain a compound represented by general formula (V) (PG-OOC-A1 -OOC-A 2 -R 1 ) is obtained. The step 2 is a step of reacting a compound represented by the general formula (III) (PG-OOC-A 1 -OH) and the compound represented by the general formula (IV) (HOOC-A 2 -R 1 ) with the carboxy group of the ester.

[0049] The compound represented by the general formula (III) (PG-OOC-A 1 A compound represented by general formula (IV) (HOOC-A -OH) is added to an intermediate composition for inhibiting deprotection, in which a nitrogen-containing basic compound having a pKa of 4 to 10 is coexisted as a deprotection inhibitor. 2 -R 1 ) is added to the reaction mixture, which suppresses side reactions and produces the compound represented by general formula (V) (PG-OOC-A 1 -OOC-A 2 -R 1 The yield of the product can be improved.

[0050] The compound represented by the general formula (IV) (HOOC-A 2 -R 1 ) can be appropriately selected and used as a commercially available product, or can be synthesized by referring to JP-A-2008-214269, EP-A-1174411, etc.

[0051] In the esterification step, the amounts of the compound represented by the general formula (III) and the compound represented by the general formula (IV) used are not particularly limited, but the compound represented by the general formula (IV) is preferably used in a ratio of 0.9 mol to 3.0 mol, more preferably 1.1 to 2.5 mol, per 1 mol of the compound represented by the general formula (III).

[0052] In the esterification step, a condensing agent may be used to carry out esterification by dehydration condensation of the compound represented by general formula (III) and the compound represented by general formula (IV).

[0053] Examples of the condensing agent include, but are not limited to, the condensing agents represented by the following chemical formulas (CA-1) to (CA-7).

[0054] [ka]

[0055] The condensing agent may be at least one selected from the condensing agents represented by the formula (CA-1), the condensing agents represented by the formula (CA-2), the condensing agents represented by the formula (CA-4), and the condensing agents represented by the formula (CA-5), and may be the condensing agent represented by the formula (CA-2), in terms of being inexpensive, easily available, and having excellent reactivity.

[0056] As the condensation agent, commercially available products may be used, and examples thereof include product codes D0436, D0437, D4029, D5347, D1601, D0254, B2771, and C0793 manufactured by Tokyo Chemical Industry Co., Ltd., and carbodiimide-based condensation agents manufactured by Wako Pure Chemical Industries, Ltd. The condensing agent may be used alone or in combination of two or more kinds.

[0057] The amount of the condensing agent used is not particularly limited, but may be 1.0 to 2.0 moles, or 1.2 to 1.7 moles, per mole of the compound represented by the general formula (III).

[0058] In the esterification step, a catalyst may be used in order to accelerate the reaction. The catalyst includes compounds having a pyridine skeleton, such as pyridine and 4-(dimethylamino)pyridine. The catalysts may be used alone or in combination of two or more.

[0059] When the catalyst is used, the amount of the catalyst used is not particularly limited, but may be 0.01 to 0.2 moles, or 0.02 to 0.1 moles, per mole of the compound represented by general formula (III).

[0060] When the deprotection suppression intermediate composition obtained in step 1 contains a compound having a pyridine skeleton capable of functioning as a catalyst in the esterification step as the nitrogen-containing basic compound having a pKa of 4 to 10, it is not necessary to further add a compound having a pyridine skeleton as a catalyst in step 2. The composition in which a compound having a pyridine skeleton functions as a catalyst in the esterification step is a compound represented by general formula (IV) (HOOC-A 2 -R 1 ) and a condensing agent, and is a composition different from the deprotection inhibiting intermediate composition obtained in step 1.

[0061] In the production method of the present disclosure, the reaction between the compound represented by the general formula (III) and the compound represented by the general formula (IV) is preferably carried out in an organic solvent. Examples of the organic solvent used in the esterification step include ketones such as acetone, 2-butanone, methyl isobutyl ketone, and cyclopentanone; cyclic ethers such as tetrahydrofuran (THF), tetrahydropyran, 1,3-dioxolane, and 1,4-dioxane; amides such as N-methyl-2-pyrrolidone (NMP), N,N-dimethylformamide (DMF), and N,N-dimethylacetamide (DMAc); sulfur-containing solvents such as dimethyl sulfoxide (DMSO) and sulfolane; and mixed solvents thereof. The organic solvent used in the esterification step may be the organic solvent contained in the deprotection suppression intermediate composition obtained in the step 1, and an appropriately selected organic solvent may be further added as necessary.

[0062] The amount of the organic solvent used is appropriately adjusted depending on the type of each compound to be reacted, and is not particularly limited; however, the amount of the organic solvent is preferably 50 to 98 mass%, and more preferably 70 to 90 mass%, of the total amount of the reaction liquid used when the compound represented by the general formula (III) and the compound represented by the general formula (IV) are subjected to a dehydration condensation reaction.

[0063] In the production method of the present disclosure, the method of reacting the compound represented by the general formula (III) with the compound represented by the general formula (IV) in the presence of a condensing agent may be, for example, a method of adding the compound represented by the general formula (IV), a condensing agent, and if necessary, a catalyst to the deprotection suppression intermediate composition obtained in the step 1 containing the compound represented by the general formula (III), and stirring the whole. Alternatively, a method of dropping a condensing agent solution obtained by dissolving a condensing agent in an organic solvent into a mixed solution obtained by adding and dissolving the compound represented by the general formula (IV) and, if necessary, a catalyst to the deprotection suppression intermediate composition obtained in the step 1 containing the compound represented by the general formula (III).

[0064] In the production method of the present disclosure, when the compound represented by the general formula (III) and the compound represented by the general formula (IV) are reacted in the presence of a condensing agent, it is preferable to carry out the reaction under an inert atmosphere such as a nitrogen stream in order to suppress side reactions. In the production method of the present disclosure, the reaction temperature when reacting the compound represented by the general formula (III) with the compound represented by the general formula (IV) in the presence of a condensing agent may be in the range of 1° C. to 30° C., or in the range of 5° C. to 20° C., in order to improve the reaction yield. The reaction time may be appropriately selected depending on the scale, and may be in the range of 10 minutes to 24 hours, or in the range of 1 hour to 20 hours.

[0065] In the manner described above, the compound represented by the general formula (III) (PG-OOC-A 1—OH) and a compound represented by the general formula (IV) (HOOC-A 2 -R 1 ) is subjected to dehydration condensation to cause an esterification reaction, thereby obtaining the compound represented by the general formula (V) (PG-OOC-A 1 -OOC-A 2 -R 1 ) can be obtained.

[0066] (3) Process 3 In the production method of the present disclosure, the compound represented by the general formula (V) (PG-OOC-A 1 -OOC-A 2 -R 1 By deprotecting the protecting group PG in the above-mentioned compound (HOOC-A), a compound represented by the following general formula (VI) (HOOC-A 1 -OOC-A 2 -R 1 ) is obtained.

[0067] In the deprotection reaction for removing the protecting group PG, it is preferable to use an acid as a deprotecting agent since it does not cleave the ester, and an inorganic acid may be used since it is inexpensive. Examples of inorganic acids include hydrochloric acid, sulfuric acid, and nitric acid, and hydrochloric acid is particularly preferable. As an acid, trifluoroacetic acid may be used from the viewpoint of promoting the reaction due to its high miscibility with the reaction solvent.

[0068] The amount of the deprotecting agent used is not particularly limited, but may be 0.1 to 4.0 moles, or 1.0 to 2.5 moles, per mole of the compound represented by the general formula (V).

[0069] In the production method of the present disclosure, the deprotection reaction is preferably carried out in an organic solvent. The organic solvent used in the deprotection reaction step may be the same as the organic solvent used in the esterification step. The organic solvent used in the deprotection reaction step may be the organic solvent contained in the reaction solution obtained in the step 2, and an appropriately selected organic solvent may be further added, if necessary.

[0070] The amount of the organic solvent used is appropriately adjusted depending on the type of each compound to be reacted, and is not particularly limited. However, the amount of the organic solvent is preferably 50 to 98 mass %, and more preferably 70 to 90 mass %, of the total amount of the reaction solution used in the deprotection reaction of the compound represented by general formula (V).

[0071] In the production method of the present disclosure, a method for deprotecting the compound represented by the general formula (V) may be, for example, a method in which a deprotecting agent is added to a solution containing the compound represented by the general formula (V) and the whole is stirred.

[0072] In the production method of the present disclosure, the deprotection reaction is preferably carried out under an inert atmosphere such as a nitrogen stream in order to suppress side reactions. In the production method of the present disclosure, the reaction temperature during the deprotection reaction may be in the range of 0° C. to 66° C., or in the range of 0° C. to 15° C., in order to improve the reaction yield. The reaction time may be appropriately selected depending on the scale, and may be in the range of 15 minutes to 48 hours, or in the range of 15 minutes to 24 hours.

[0073] From the viewpoint of removing impurities after the deprotection reaction, it is preferable to further include a step of precipitating the compound represented by the general formula (VI) from a solution containing the compound represented by the general formula (VI) (in the present disclosure, this step may be referred to as a precipitation step). As a method for precipitating the compound represented by the general formula (VI), from the viewpoint of removing impurities, a method of adding a poor solvent for the compound represented by the general formula (VI) to a solution containing the compound represented by the general formula (VI) and cooling it as necessary can be mentioned. After the precipitating step, the target compound can be obtained as a solid by obtaining the precipitate by filtration or the like.

[0074] The solution containing the compound represented by the general formula (VI) may be a filtrate obtained by removing unnecessary substances by filtration as necessary, or may be a concentrated solution of the solution containing the compound represented by the general formula (VI), a concentrated solution of the filtrate, or a solution obtained by distilling off the solvent from the filtrate and redissolving the solid in a different solvent. From the viewpoint of improving the yield of the compound represented by the general formula (VI), the solution containing the compound represented by the general formula (VI) to which a poor solvent is added may be about 5 g to 50 g, or may be 10 g to 20 g, relative to the theoretical yield (mass 1 g) of the compound represented by the general formula (VI).

[0075] The poor solvent is selected with a solubility (25° C.) of less than 3 g / 100 g (compound represented by the general formula (VI) above / solvent) as a guide. The poor solvent may be an alcohol-based solvent, since it is inexpensive, has a low risk of electrostatic fire, and has a high purification effect. Examples of the alcohol solvent used in the precipitation step include methanol, ethanol, 1-propanol, 2-propanol, 1-butanol, and 2-butanol. The alcohol-based solvent may be selected from the group consisting of methanol, ethanol, 2-propanol, and combinations thereof, particularly from the viewpoint of ease of removal by drying, and may further be selected from the group consisting of methanol, 2-propanol, and combinations thereof.

[0076] The method for adding the poor solvent to the solution containing the compound represented by the general formula (VI) is not particularly limited, and the poor solvent may be added all at once or dropwise. The amount of the alcohol solvent added is not particularly limited, but from the viewpoint of improving the yield, it is about 5 to 50 times (mass ratio), preferably 10 to 20 times (mass ratio), and more preferably 10 to 15 times (mass ratio) relative to the solution containing the compound represented by the general formula (VI).

[0077] The temperature of the solution containing the compound represented by the general formula (VI) after adding a poor solvent is preferably kept in the range of 0 to 25°C, more preferably in the range of 0 to 10°C, in terms of improving the yield. From the viewpoint of improving the yield, the solution after the addition of the alcohol solvent is preferably stirred for an appropriate time at 0 to 25° C. The stirring time is not particularly limited and varies depending on conditions such as the reaction scale, the amount of solvent, and the temperature, but is usually 1 to 24 hours.

[0078] The method for recovering the precipitated solid is not particularly limited, and may be, for example, a method by filtration. As the filtration method, for example, a known method such as reduced pressure filtration, pressure filtration, centrifugal filtration, etc. may be applied, and is not particularly limited. In addition, after filtering the solid compound represented by the general formula (VI), the solid may be washed with a washing solvent, which may be a poor solvent such as the alcohol-based solvent. The obtained solid is preferably dried at 15°C to 70°C, for example, by a blower dryer. The purity of the solid obtained by drying can be confirmed by HPLC, and the structure of the solid obtained by drying can be identified by NMR, mass spectrometry, or the like.

[0079] (4) Process 4 The manufacturing method of the present disclosure includes: 1 and E 2 With a binaphthol which may have at least one of the following. Substituent E 1 and E 2 The binaphthol which may have at least one of the following substituents can be appropriately selected and used from commercially available products. 1 and E 2 Binaphthol which may have at least one of the above can be synthesized by referring to JP-A-2003-231659, etc.

[0080] A compound represented by the general formula (VI) and a substituent E1 and E 2 As a method for obtaining an optically active compound having a binaphthol moiety represented by the general formula (I) by reacting a compound represented by the general formula (VI) with a binaphthol which may have at least one of the substituents E 1 and E 2 and a binaphthol which may have at least one of the following in an organic solvent, thereby obtaining an optically active compound having a binaphthol moiety represented by the general formula (I). In step 4, a compound represented by the general formula (VI) and a substituent E 1 and E 2 The amount of binaphthol used may be determined by the amount of the substituent E 1 and E 2 It is preferable that the compound represented by the general formula (VI) is used in an amount of 2.0 to 3.0 moles per mole of the binaphthol which may have at least one of the following.

[0081] In step 4, the compound represented by the general formula (VI) and the substituent E 1 and E 2 The condensation agent used in the esterification in step 4 may be the same as the condensation agent used in the esterification in step 2. The amount of the condensation agent used is appropriately adjusted and is not particularly limited, but may be 1.0 mol to 2.5 mol per mol of the compound represented by the general formula (VI).

[0082] Furthermore, in order to accelerate the reaction, a catalyst may be used in the esterification step in step 4. As the catalyst, the same catalyst as that used in the esterification step in step 2 can be used. When the catalyst is used, the amount of the catalyst used is not particularly limited, but may be 0.01 to 0.2 moles, or 0.02 to 0.1 moles, per mole of the compound represented by general formula (VI).

[0083] In the production method of the present disclosure, a compound represented by the general formula (VI) and a substituent E 1 and E 2 The reaction with binaphthol, which may have at least one of the following, is preferably carried out in an organic solvent. Examples of the organic solvent used in the esterification step include ketones such as acetone, 2-butanone, methyl isobutyl ketone, and cyclopentanone; cyclic ethers such as tetrahydrofuran (THF), tetrahydropyran, 1,3-dioxolane, and 1,4-dioxane; amides such as N-methyl-2-pyrrolidone (NMP), N,N-dimethylformamide (DMF), and N,N-dimethylacetamide (DMAc); sulfur-containing solvents such as dimethyl sulfoxide (DMSO) and sulfolane; and mixed solvents thereof.

[0084] The amount of the organic solvent used is appropriately adjusted and is not particularly limited, but may be 3 parts by mass to 50 parts by mass relative to 1 part by mass of the compound represented by general formula (VI), It may be used in an amount of 5 parts by weight to 10 parts by weight.

[0085] In the production method of the present disclosure, a compound represented by the general formula (VI) and a substituent E 1 and E 2 When reacting the binaphthol, which may have at least one of the following, in the presence of a condensing agent, it is preferable to carry out the reaction in an inert atmosphere such as a nitrogen stream in order to suppress side reactions. A compound represented by the general formula (VI) and a substituent E 1 and E 2 The reaction temperature when reacting with binaphthol which may have at least one of the following is preferably -20°C to 30°C, more preferably -10°C to 20°C. The reaction time is appropriately adjusted depending on the reaction scale, etc., but is usually 30 minutes to 24 hours.

[0086] As described above, the compound represented by the general formula (VI) (HOOC-A 1-OOC-A 2 -R 1 ) and the substituent E 1 and E 2 By dehydration condensation with a binaphthol which may have at least one of the above, an esterification reaction occurs, and an optically active compound having a binaphthol moiety represented by the above general formula (I) can be obtained.

[0087] The solution containing the optically active compound having a binaphthol moiety represented by the general formula (I) is preferably neutralized with an acid in order to improve the purity. The acid used for neutralization is not particularly limited, and examples thereof include acetic acid, hydrochloric acid, sulfuric acid, and phosphoric acid.

[0088] It is preferable to isolate the optically active compound having a binaphthol moiety represented by the general formula (I) from the solution containing the optically active compound having a binaphthol moiety represented by the general formula (I) after neutralization. As a method for isolating an optically active compound having a binaphthol moiety represented by the general formula (I), in terms of ease of operation, it is preferable to include a step of adding a poor solvent for the optically active compound having a binaphthol moiety represented by the general formula (I) to a solution containing the optically active compound having a binaphthol moiety represented by the general formula (I), thereby precipitating the optically active compound having a binaphthol moiety represented by the general formula (I). The step of precipitating the optically active compound having a binaphthol moiety represented by the general formula (I) by adding an alcoholic solvent as a poor solvent may be the same as the step of precipitating the compound represented by the general formula (VI) by adding a poor solvent in the step 3. After the precipitation step, the precipitate is obtained by filtration or the like, whereby the optically active compound having a binaphthol moiety represented by the general formula (I) can be obtained as a solid.

[0089] The purity of the solid obtained by drying can be confirmed by HPLC, and the structure of the solid obtained by drying can be identified by NMR, mass spectrometry, or the like.

[0090] (5) Process 5 The production method of the present disclosure may further include a step of recrystallizing and purifying the optically active compound having a binaphthol moiety represented by general formula (I) obtained in step 4 in order to achieve higher purity. For the recrystallization purification of the optically active compound having a binaphthol moiety represented by the general formula (I), for example, the following mixture may be prepared in terms of yield and impurity removal ability: That is, a mixture may be prepared by adding an ester-based, ether-based, ketone-based, or halogen-based solvent such as isopropyl acetate, 1,3-dioxolane, cyclopentanone, or chloroform as an organic solvent for dissolving the compound to the compound represented by the general formula (VI), and further adding dibutylhydroxytoluene, methylhydroquinone, or the like as a polymerization inhibitor, and activated clay, activated carbon, or the like as an impurity adsorbent or decolorizing agent.

[0091] The amount of the organic solvent may be about 5 g to 30 g, or may be 5 g to 15 g, per 1 g of the mass of the optically active compound having a binaphthol moiety represented by the general formula (I). The amount of the polymerization inhibitor may be about 0.00001 g to 0.1 g, or may be 0.0001 g to 0.0005 g, per 1 g of the mass of the optically active compound having a binaphthol moiety represented by the general formula (I). The amount of the impurity adsorbent or decolorizing agent may be about 0.01 g to 10 g, or may be 0.05 g to 0.5 g, per 1 g of the mass of the optically active compound having a binaphthol moiety represented by the general formula (I).

[0092] In order to improve the purity, the mixture may be heated to 30° C. to 100° C. and filtered through diatomaceous earth to remove dust and recover the filtrate. By performing diatomaceous earth filtration, the content of impurities can be reduced. In addition, diatomaceous earth filtration refers to filtration using diatomaceous earth as a filter aid. In the diatomaceous earth filtration performed in the manufacturing method of the present disclosure, it is preferable to use a precoat method in which diatomaceous earth is filled or attached to the surface of a filter medium such as filter paper in advance to form a diatomaceous earth layer. In the diatomaceous earth filtration step, the diatomaceous earth used as a filter aid is not particularly limited, but examples thereof include Celite (registered trademark), Dicalite (registered trademark), Radiolite (registered trademark), and Cellpure (registered trademark). For example, commercially available Celite (registered trademark) products include, for example, Filter-Cel, Celite 505, Standard Super-Cel, Celite 512, Hyflo Super-Cel, Celite 503, Celite 535, Celite 545, and Celite 577 manufactured by Imerys; Celite 535, Celite 545, Standard Super-Cel, and Hyflo Super-Cel manufactured by Junsei Chemical Co., Ltd.; and Celite, Celite 503, Celite 535, and Celite 545 manufactured by Kanto Chemical Co., Ltd. The diatomaceous earth may be used alone or in combination of two or more kinds.

[0093] It is preferable to include a step of adding an alcohol-based solvent, which is a poor solvent for the optically active compound having a binaphthol moiety represented by the general formula (I), to the recovered filtrate, thereby precipitating a solid of the optically active compound having a binaphthol moiety represented by the general formula (I). The step of precipitating a solid of the optically active compound having a binaphthol moiety represented by the general formula (I) by adding an alcoholic solvent as a poor solvent may be the same as the step of precipitating a solid of the compound represented by the general formula (VI) by adding a poor solvent in the step 3.

[0094] In the present disclosure, the structure of each compound can be analyzed by an appropriate combination of nuclear magnetic resonance spectroscopy (NMR), pyrolysis-type gas chromatography-mass spectrometry (Py-GC-MS), matrix-assisted laser desorption / ionization time-of-flight mass spectrometry (MALDI-TOFMS), elemental analysis, and the like.

[0095] 3.Applications The optically active compound having a binaphthol moiety represented by the general formula (I) obtained by the production method of the present disclosure can be suitably used in a polymerizable cholesteric liquid crystal composition. In addition, the polymerizable cholesteric liquid crystal composition containing the optically active compound having a binaphthol moiety represented by the general formula (I) obtained by the production method of the present disclosure can be suitably used for various optical component applications such as electromagnetic wave reflection films, brightness improvement films for displays, and heat ray shielding films. EXAMPLES

[0096] <pKa measurement of nitrogen-containing basic compounds> The pKa was determined by acid-base titration as follows: In an environment of 25°C, 0.100g of a sample to be measured for pKa was precisely weighed into a 250mL conical beaker, 150mL of tetrahydrofuran / water = 6 / 4 (volume ratio) was added, and the solution was dissolved for 30 minutes to obtain a measurement solution. 10μL of 0.1mol / L potassium hydroxide ethyl alcohol solution (e.g. Fuji Film Wako) was added at a time, and titration was performed while reading the pH each time. 0.1mol / L potassium hydroxide ethyl alcohol solution was added until the pH became 10 or higher and there was no change in pH even after adding 30μL. From the obtained results, the pH was plotted against the amount of 0.1mol / L potassium hydroxide ethyl alcohol solution added, and a titration curve was obtained. The point where the slope of the pH change was the largest from the obtained titration curve was determined as the neutralization point, and the pH at half the amount of 0.1mol / L potassium hydroxide ethyl alcohol solution added required to reach the neutralization point was read from the titration curve, and the pH value read was determined as the pKa.

[0097] In the following, the compounds prepared and isolated are 1The chemical structure was confirmed by H-NMR measurement. <NMR measurement conditions> NMR (nuclear magnetic resonance apparatus): AVANCE (400 MHz) manufactured by Bruker Approximately 5 mg of the sample was dissolved in 0.6 mL of a deuterated solvent and sealed in an NMR sample tube. The nuclei measured by NMR 1 H was measured with 16 accumulations, and the obtained signals were analyzed with the TMS signal added to the deuterated solvent set at 0.00 ppm.

[0098] Also, the purity of the compound in each synthesis step was analyzed by high performance liquid chromatography (HPLC). <HPLC measurement conditions> HPLC (high performance liquid chromatograph): LC2010CHT manufactured by Shimadzu Corporation · Column: YMC-Pack Pro C18 s 4.6×250 mm · Column temperature: 40 °C · Mobile phase A: acetonitrile / water (volume ratio 50:50) · Mobile phase B: acetonitrile / THF (volume ratio 50:50) · Concentration gradient of mobile phases A and B (volume ratio): 0 min (A / B = 80 / 20) → 20 min (A / B = 0 / 100) → 25 min (A / B = 0 / 100) → 30 min (A / B = 80 / 20) → 35 min (A / B = 80 / 20) · Flow rate: 1.0 mL / min Detection wavelength: 224 nm (UV)

[0099] Also, the optical purity of the optically active compound was analyzed by high performance liquid chromatography (HPLC) under the following measurement conditions. <HPLC measurement conditions> · Column: CHIRALPACK IB 4.6×250 mm · Column temperature: 40 °C · Mobile phase A: acetonitrile / water (volume ratio 50:50) · Mobile phase B: acetonitrile / THF (volume ratio 50:50) Concentration gradient of mobile phase A and B (volume ratio): 0 min (A / B=80 / 20) → 20 min (A / B=50 / 50) → 30 min (A / B=0 / 100) → 45 min (A / B=80 / 20) → 50 min (A / B=80 / 20) Flow rate: 1.0mL / min Detection wavelength: 224nm (UV)

[0100] [Example 1] (1) Step 1: Synthesis of compound a1 (preparation of intermediate composition for suppressing introduction of protecting group and deprotection) 2.0 g of 4-(4-hydroxyphenyl)benzoic acid (Tokyo Chemical Industry Co., Ltd.) and 13.3 g of tetrahydrofuran (THF, Kanto Chemical Co., Ltd.) were added to the flask, stirring was started, and the mixture was cooled to 15°C. After cooling, 1.0 g of chloromethyl ethyl ether (Tokyo Chemical Industry Co., Ltd.) was added to the flask. Next, 1.4 g of N,N-diisopropylethylamine (Tokyo Chemical Industry Co., Ltd.) was added dropwise to the flask, and the mixture was stirred and reacted at 15°C to obtain a THF solution of the following compound a1. The reaction was started when the addition of N,N-diisopropylethylamine was completed, and the reaction solution was sampled every 15 minutes from 30 minutes after the start of the reaction, and the reaction solution samples were subjected to HPLC measurement. The reaction was completed when the peak of the raw material 4-(4-hydroxyphenyl)benzoic acid was 0.1 Area% or less. The reaction was completed 60 minutes after the start of the reaction. Immediately after (within 5 seconds) confirming the end point of the reaction by HPLC measurement, i.e., 45 minutes after sampling at the end point of the reaction, 0.1 g of 4-dimethylaminopyridine (DMAP, Tokyo Chemical Industry Co., Ltd.) was added to the THF solution of compound a1 to prepare intermediate composition 1 for inhibiting deprotection. When confirmed by HPLC, the purity of compound a1 in deprotection suppressing intermediate composition 1 was 97.5 Area % (the raw material 4-(4-hydroxyphenyl)benzoic acid was 0.1 Area %).

[0101] [ka]

[0102] (2) Step 2: Synthesis of compound b1 While the deprotection suppression intermediate composition 1 (a THF solution of compound a1 and DMAP) in the flask obtained in step 1 was maintained at 15 ° C., 180 minutes after the deprotection suppression intermediate composition 1 was obtained (45 minutes after the end of the reaction), 3.0 g of 4-(4-acryloyloxybutoxy)benzoic acid (Fujifilm Wako Pure Chemical Industries, Ltd.) and 1.4 g of N,N'-diisopropylcarbodiimide (DIC, Tokyo Chemical Industry Co., Ltd.) were added at 15 ° C. The mixture was stirred at 15 ° C. for 10 hours to react, and a THF solution of compound b1 was obtained. The amount of 4-(4-acryloyloxybutoxy)benzoic acid charged was calculated on the assumption that the theoretical amount of compound a1 in the THF solution was 2.54 g. When confirmed by HPLC, the purity of compound b1 in the solution was 97.0 Area % (compound a1 was 2.0 Area %).

[0103] [ka]

[0104] (3) Step 3: Synthesis of compound c1 (deprotection reaction) 2.4 g of 35% hydrochloric acid (Kanto Chemical Co., Ltd.) was added to the THF solution of compound b1 in the flask obtained in step 2 at 15° C., and the mixture was stirred at 15° C. for 8 hours to react. 60.2 g of methanol was added dropwise to the obtained reaction solution, and a white solid was obtained by filtration. The white solid was then dried at 50° C. with a blower dryer to obtain 4.2 g of compound c1. The amount of 35% hydrochloric acid charged was calculated assuming that the theoretical amount of compound b1 in the THF solution was 4.8 g.

[0105] When the quality was confirmed by HPLC, the purity of compound c1 in the solution was 99.0 Area %. 1H-NMR of compound c1 (DMSO-D6):σ(ppm) 1.75-1.90(m,4H),4.10-4.20(t,2H),4.20-4.30(t,2H),5.90-6.00(dd,1H),6.10-6.25(m,1H),6.25-6.40(dd, 1H), 7.05-7.15(m, 2H), 7.35-7.50(m, 2H), 7.75-7.95(m, 4H), 8.00-8.10(m, 2H), 8.10-8.20(m, 2H), 13.00(s, 1H)

[0106] [ka]

[0107] (4) Step 4: Synthesis of optically active compound 1 having a binaphthol moiety Into a flask, 0.4 g of (R)-(+)-1,1'-bi-2-naphthol ((R)-BINOL, Tokyo Chemical Industry Co., Ltd.), 1.46 g of compound c1, 0.03 g of DMAP, and 9.3 g of 1,3-dioxolane were added, and the mixture was cooled to 10°C. After cooling, 0.5 g of DIC was added dropwise to the mixture, and the mixture was reacted at 10°C for 15 hours. The resulting reaction solution was cooled to 0°C, and 0.03 g of 35% hydrochloric acid was added to the reaction solution to neutralize it, and then 11.1 g of methanol was added dropwise to the reaction solution over 1 hour. After adding methanol dropwise, the reaction solution was stirred for 1 hour, and then a white solid was obtained by filtration. Next, the white solid was dried at 50°C with a blower dryer, and 1.3 g of optically active compound 1 having a binaphthol moiety was obtained.

[0108] When confirmed by HPLC, the purity of Compound 1 in the solution was 99.5%. In addition, when the optical purity was measured, no enantiomers were detected. 1H-NMR of compound 1 (CDCl3):σ(ppm) 1.80-2.00(m,8H),4.05-4.20(t,4H),4.20-4.35(t,4H),5.80-5.90(dd,2H),6.05-6.2(m,2H),6.35-6.50(dd,2H),6.90-7.05(m,4H) , 7.20-7.30(m, 4H), 7.30-7.50(m, 10H), 7.50-7.70(m, 6H), 7.70-7.80(m, 4H), 7.90-7.95(m, 2H), 8.00-8.05(m, 2H), 8.10-8.20(m, 4H)

[0109] [ka]

[0110] (5) Step 5: Recrystallization purification of compound 1 In a flask, 1.3 g of the optically active compound 1 having a binaphthol moiety obtained in the above step 4, 0.0005 g of dibutylhydroxytoluene (BHT, Tokyo Chemical Industry Co., Ltd.), 9.0 g of isopropyl acetate (Tokyo Chemical Industry Co., Ltd.), 0.1 g of activated clay (Fujifilm Wako Pure Chemical Industries, Ltd.), and 0.1 g of activated carbon (Darco G-60, Fujifilm Wako Pure Chemical Industries, Ltd.) were added, and the mixture was heated to 60 ° C. The mixture was filtered to remove dust using Celite (Celite 503, Kanto Chemical Co., Ltd.), and the filtrate was collected. After cooling the filtrate to 25 ° C., 15 g of methanol was added, and after confirming that the solution was a slurry, the mixture was filtered and the solid was collected. The collected solid was dried at 50 ° C. with a blower dryer to obtain 1.2 g of a purified product of the optically active compound 1 having a binaphthol moiety. When the quality was confirmed by HPLC, the purified product of the optically active compound 1 having a binaphthol moiety in the solution had a purity of 99.9%. In addition, when the optical purity was measured, no enantiomers were detected. The yield of the optically active compound 1 having a binaphthol moiety relative to 4-(4-hydroxyphenyl)benzoic acid was 65%.

[0111] [Example 2] In Example 1, except that 0.4 g of (S)-(-)-1,1'-bi-2-naphthol ((S)-BINOL, Tokyo Chemical Industry Co., Ltd.) was used instead of 0.4 g of (R)-(+)-1,1'-bi-2-naphthol ((R)-BINOL, Tokyo Chemical Industry Co., Ltd.), 1.3 g of an optically active compound 2 having a binaphthol moiety was obtained as a white solid in the same manner as in Example 1. After recrystallization and purification, the quality was confirmed by HPLC, and the purified product of the optically active compound 2 having a binaphthol moiety in the solution had a purity of 99.5 Area %. In addition, when the optical purity was measured, no enantiomers were detected. The yield of the optically active compound 2 having a binaphthol moiety relative to 4-(4-hydroxyphenyl)benzoic acid was 65%.

[0112] [Example 3] (1) Step 1: Synthesis of compound a1 (preparation of intermediate composition for suppressing introduction of protecting group and deprotection) 2.0 g of 4-(4-hydroxyphenyl)benzoic acid (Tokyo Chemical Industry Co., Ltd.) and 13.4 g of THF were added to the flask, stirring was started, and the mixture was cooled to 15°C. After cooling, 1.0 g of chloromethyl ethyl ether was added to the flask. Next, 1.4 g of N,N-diisopropylethylamine was added dropwise to the flask, and the mixture was stirred at 15°C to react, thereby obtaining a THF solution of the following compound a1. The reaction was started when the addition of N,N-diisopropylethylamine was completed, and the reaction solution was sampled every 15 minutes from 30 minutes after the start of the reaction, and the reaction solution samples were subjected to HPLC measurement. The reaction was completed when the reaction solution was sampled at a peak of 0.1 Area% or less of the raw material 4-(4-hydroxyphenyl)benzoic acid. The reaction was completed 60 minutes after the start of the reaction. Immediately after (within 5 seconds) confirming the end of the reaction by HPLC measurement, i.e., 45 minutes after sampling at the end of the reaction, 0.07 g of morpholine (Kanto Chemical Co., Ltd.) was added to the THF solution of compound a1 to prepare intermediate composition 3 for inhibiting deprotection. When confirmed by HPLC, the purity of compound a1 in deprotection suppression intermediate composition 3 was 98.7 Area % (the raw material 4-(4-hydroxyphenyl)benzoic acid was 0.1 Area %).

[0113] [ka]

[0114] (2) Step 2: Synthesis of compound b1 While the deprotection suppression intermediate composition 3 (a THF solution of compound a1 and morpholine) in the flask obtained in step 1 was maintained at 15 ° C., 180 minutes after the deprotection suppression intermediate composition 3 was obtained (45 minutes after the end of the reaction), 3.0 g of 4-(4-acryloyloxybutoxy)benzoic acid (Fujifilm Wako Pure Chemical Industries, Ltd.), 1.4 g of N,N'-diisopropylcarbodiimide (DIC, Tokyo Chemical Industry Co., Ltd.), and 0.11 g of DMAP were added at 15 ° C. The mixture was reacted for 10 hours at 15 ° C. to obtain a THF solution of compound b1. The amount of 4-(4-acryloyloxybutoxy)benzoic acid charged was calculated on the assumption that the theoretical amount of compound a1 in the THF solution was 2.54 g. When the quality was confirmed by HPLC, the purity of compound b1 in the solution was 97.9 Area % (compound a1 was 2.0 Area %).

[0115] (3) Process 3~Process 5 Steps 3 to 5 were carried out in the same manner as in Example 1. After the recrystallization purification in step 5, the quality was confirmed by HPLC, and the purified product of the optically active compound 1 having a binaphthol moiety in the solution had a purity of 99.9 Area %. In addition, when the optical purity was measured, no enantiomers were detected. The yield of the optically active compound 1 having a binaphthol moiety relative to 4-(4-hydroxyphenyl)benzoic acid was 70%.

[0116] [Example 4] (1) Step 1: Synthesis of compound a1 (preparation of intermediate composition for suppressing introduction of protecting group and deprotection) Step 1 was carried out in the same manner as in Example 1. (2) Step 2: Synthesis of compound b1 While the deprotection suppression intermediate composition 1 (a THF solution of compound a1 and DMAP) in the flask obtained in step 1 was maintained at 15 ° C., 16 hours after the deprotection suppression intermediate composition 1 was obtained (45 minutes after the end of the reaction), 3.0 g of 4-(4-acryloyloxybutoxy)benzoic acid (Fujifilm Wako Pure Chemical Industries, Ltd.) and 1.4 g of N,N'-diisopropylcarbodiimide (DIC, Tokyo Chemical Industry Co., Ltd.) were added at 15 ° C. The mixture was reacted for 10 hours at 15 ° C. to obtain a THF solution of compound b1. The amount of 4-(4-acryloyloxybutoxy)benzoic acid charged was calculated on the assumption that the theoretical amount of compound a1 in the THF solution was 2.54 g. When the quality was confirmed by HPLC, the purity of compound b1 in the solution was 97.0 Area % (compound a1 was 2.0 Area %).

[0117] (3) Process 3~Process 5 Steps 3 to 5 were carried out in the same manner as in Example 1. After the recrystallization purification in step 5, the quality was confirmed by HPLC, and the purified product of the optically active compound 1 having a binaphthol moiety in the solution had a purity of 99.9 Area %. In addition, when the optical purity was measured, no enantiomers were detected. The yield of the optically active compound 1 having a binaphthol moiety relative to 4-(4-hydroxyphenyl)benzoic acid was 65%.

[0118] [Comparative Example 1] (1) Step 1: Synthesis of compound a1 (introduction of a protecting group) Compound a1 was synthesized in the same manner as in step 1 of Example 1, except that in step 1 of Example 1, 0.1 g of 4-dimethylaminopyridine was not added and the intermediate composition for inhibiting deprotection was not prepared. The THF solution of compound a1 was kept at 15°C, and 16 hours after the THF solution of compound a1 was obtained (45 minutes after the end of the reaction), the quality was confirmed by HPLC, and the purity of compound a1 in the solution was 60.0 Area% (the raw material 4-(4-hydroxyphenyl)benzoic acid was 0.1 Area%). Furthermore, it was revealed that by-product 1 having the following structure was produced at 37.0 Area%.

[0119] By-product 1 was isolated and 1 Identification was performed using H-NMR. By-product 1 1 H-NMR (heavy DMSO): σ(ppm)1.10-1.20(d,3H),3.65-3.75(q,2H), 5.32(s,2H), 7.10-7 .20(d,2H), 7.70-7.80(d,2H), 8.10-8.20(d,2H), 8.20-8.30(d,2H), 13.0(s, 1H)

[0120] [ka] (2) Step 2: Synthesis of compound b1 While the THF solution of compound a1 in the flask obtained in step 1 was maintained at 15°C, 16 hours after the THF solution of compound a1 was obtained (reaction end point + 45 minutes), 3.0g of 4-(4-acryloyloxybutoxy)benzoic acid (Fujifilm Wako Pure Chemical Industries, Ltd.), 1.4g of N,N'-diisopropylcarbodiimide (DIC, Tokyo Chemical Industry Co., Ltd.), and 0.11g of DMAP were added at 15°C. The mixture was reacted for 10 hours at 15°C to obtain a THF solution of compound b1. The amount of 4-(4-acryloyloxybutoxy)benzoic acid charged was calculated assuming that the theoretical amount of compound a1 in the THF solution was 2.54g. When the quality was confirmed by HPLC, the purity of compound b1 in the solution was 60.1 Area % (compound a1 was 2.0 Area %). Furthermore, it was revealed that by-product 2 having the following structure, which is generated by condensation of by-product 1 with compound a1, was generated at 14.5 Area %.

[0121] By-product 2 was isolated and 1 Identification was performed using H-NMR. By-product 2 1 H-NMR (heavy DMSO): σ (ppm) 1.10-1.20 (dt, 6H), 3.65-3.75 (q, 2H), 3.75-3.85 (q, 2H), 5.32 (s, 2H), 5.54 (s, 2H), 7. 10-7.20(d,2H), 7.40-7.50(d,2H), 7.70-7.80(d,2H), 7.85-8.0(m,6H), 8.10-8.20(d,2H), 8.20-8.30(d,2H)

[0122] [ka]

[0123] (3) Process 3~Process 5 Steps 3 to 5 were carried out in the same manner as in Example 1. After the recrystallization purification in step 5, the quality was confirmed by HPLC, and the purified product of the optically active compound 1 having a binaphthol moiety in the solution had a purity of 60.0 Area %. In addition, when the optical purity was measured, no enantiomers were detected. The yield of the optically active compound 1 having a binaphthol moiety relative to 4-(4-hydroxyphenyl)benzoic acid was 33%.

[0124] [Comparative Example 2] (1) Step 1: Synthesis of compound a1 (introduction of a protecting group) Compound a1 was synthesized in the same manner as in step 1 of Example 1, except that in step 1 of Example 1, 0.1 g of 4-dimethylaminopyridine was not added and the intermediate composition for inhibiting deprotection was not prepared. When confirmed by HPLC, the purity of compound a1 in the solution was 97.4 Area % (the raw material 4-(4-hydroxyphenyl)benzoic acid was 0.1 Area %). Furthermore, it was revealed that the by-product 1 was generated at 0.03 Area %.

[0125] (2) Step 2: Synthesis of compound b1 While the THF solution of compound a1 in the flask obtained in step 1 was maintained at 15°C, 180 minutes after the THF solution of compound a1 was obtained (reaction end point + 45 minutes), 3.0g of 4-(4-acryloyloxybutoxy)benzoic acid (Fujifilm Wako Pure Chemical Industries, Ltd.), 1.4g of N,N'-diisopropylcarbodiimide (DIC, Tokyo Chemical Industry Co., Ltd.), and 0.11g of DMAP were added at 15°C. The mixture was reacted for 10 hours at 15°C to obtain a THF solution of compound b1. The amount of 4-(4-acryloyloxybutoxy)benzoic acid charged was calculated on the assumption that the theoretical amount of compound a1 in the THF solution was 2.54g. When the quality was confirmed by HPLC, the purity of compound b1 in the solution was 82.6 Area % (compound a1 was 2.0 Area %).

[0126] (3) Process 3~Process 5 Steps 3 to 5 were carried out in the same manner as in Example 1. After the recrystallization purification in step 5, the quality was confirmed by HPLC, and the purified product of the optically active compound 1 having a binaphthol moiety in the solution had a purity of 81.1 Area %. The yield of the optically active compound 1 having a binaphthol moiety relative to 4-(4-hydroxyphenyl)benzoic acid was 46%.

[0127] [Examples 5 to 14] A deprotection suppression intermediate composition was prepared in the same manner as in Example 1, except that in Example 1, 1.0 g of chloromethyl ethyl ether was used as the protecting group introducing agent, and the protecting group introducing agent shown in Table 2 was changed to the amount of the protecting group introducing agent shown in the table. The purity of the compound represented by general formula (III) in the deprotection inhibiting intermediate composition, measured in the same manner as in Examples 1 and 3, is also shown in Table 2.

[0128] [Table 2]

[0129] [Examples 15 to 20, Comparative Example 3: Evaluation of the stability of the protecting group of compound a1] In Example 15, a deprotection inhibiting intermediate composition was prepared in the same manner as in step 1 of Example 3. In Example 18, a deprotection inhibiting intermediate composition was prepared in the same manner as in step 1 of Example 1. In Examples 16, 17, 19 and 20, deprotection suppression intermediate compositions were prepared in the same manner as in Example 1, except that in step 1 of Example 1, as the nitrogen-containing basic compound having a pKa of 4 to 10 added at the end of the protecting group introduction reaction, 0.1 g of DMAP was used, and the amount of the nitrogen-containing basic compound having a pKa of 4 to 10 listed in Table 3 was changed to the amount of the nitrogen-containing basic compound having a pKa of 4 to 10 listed in Table 3. The purity of the compound represented by general formula (III) in the deprotection inhibiting intermediate composition was measured after storing the deprotection inhibiting intermediate composition in an environment of 25°C and 40% humidity for 5 hours and after storing the composition in an environment of 25°C and 40% humidity for 16 hours. The results of the purity of the compound represented by general formula (III) in the deprotection inhibiting intermediate composition are also shown in Table 3.

[0130] [Table 3]

[0131] In an example having a step of adding a nitrogen-containing basic compound having a pKa of 4 to 10 at the completion of a protecting group introduction reaction for synthesizing a compound represented by general formula (III) to prepare an intermediate composition for suppressing deprotection, which contains the compound represented by general formula (III) and a nitrogen-containing basic compound having a pKa of 4 to 10, it was revealed that an optically active compound having a binaphthol moiety having a specific structure containing a polymerizable group can be produced efficiently in a high yield with fewer by-products, as compared with a comparative example in which a nitrogen-containing basic compound having a pKa of 4 to 10 is not added at the completion of a protecting group introduction reaction. In addition, in the examples, it was shown that even if the type of protecting group is changed, deprotection can be suppressed by preparing an intermediate composition for suppressing deprotection containing various compounds represented by the general formula (III) and a nitrogen-containing basic compound having a pKa of 4 to 10. Furthermore, in the examples, it was shown that even when the type of nitrogen-containing basic compound having a pKa of 4 to 10 was changed, when various deprotection inhibiting intermediate compositions containing a compound represented by the general formula (III) and a nitrogen-containing basic compound having a pKa of 4 to 10 were prepared, the storage stability was increased at the end of the protecting group introduction reaction compared to a comparative example in which a nitrogen-containing basic compound having a pKa of 4 to 10 was not added. It was shown that the deprotection inhibiting intermediate composition of the present disclosure can produce an optically active compound having a binaphthol moiety having a specific structure containing a polymerizable group in high yield, even when the composition is stored once after step 1 and before step 2 is performed.

Claims

1. The following general formula (I) 【Chemistry 1】 (In the general formula (I), A １ each independently represents a 4,4'-biphenylene group, a 1,4-phenylene group, a 1,4-cyclohexylene group, or a naphthalene-2,6-diyl group; A ２ each independently represents a 4,4'-biphenylene group, a 1,4-phenylene group, a 1,4-cyclohexylene group, or a naphthalene-2,6-diyl group; A １ and A ２ each independently may have a substituent E, R １ each independently represents a group selected from general formula (R-1), General formula (R-1): -L ｒ１ -R ｓｐ１ -Z １ In general formula (R-1), L ｒ１ represents -O-, -S-, -COO-, -OCO-, -OCOO-, or a single bond; R ｓｐ１ is one -CH ２ - or two or more non-adjacent -CH ２ each independently represents an alkylene group having 1 to 20 carbon atoms which may be replaced by —O—, —COO—, or —OCO—, or a single bond; Z １ represents a polymerizable functional group. Substituents E, E １ and E ２ each independently represents an alkyl group having 1 to 3 carbon atoms or a halogen, and m1 and m2 each independently represent an integer of 0 to 2. A method for producing an optically active compound having a binaphthol moiety represented by the following formula: The following general formula (II) 【Chemistry 2】 (In the formula, A １ represents the same meaning as above.) and a carboxylic acid protecting group introducing agent to obtain a compound represented by the following general formula (III): 【Chemistry 3】 (In the formula, PG represents a protecting group, A １ represents the same meaning as above.) adding a nitrogen-containing basic compound having a pKa of 4 to 10 at the completion of a protecting group introduction reaction for synthesizing a compound represented by the general formula (III) to prepare a deprotection suppressing intermediate composition containing the compound represented by the general formula (III) and a nitrogen-containing basic compound having a pKa of 4 to 10; The deprotection suppression intermediate composition is added to a compound represented by the following general formula (IV): 【Chemistry 4】 (In the formula, A ２ , and R １ Each has the same meaning as above.) and reacting the compound represented by the following general formula (V): 【Chemistry 5】 (Wherein, PG, A １ , A ２ , and R １ Each has the same meaning as above.) and obtaining a compound represented by the formula: By deprotecting the protecting group in the compound represented by the general formula (V), a compound represented by the following general formula (VI) can be obtained. 【Chemistry 6】 (In the formula, A １ , A ２ , and R １ Each has the same meaning as above.) and obtaining a compound represented by the formula: A compound represented by the general formula (VI) and a substituent E １ and E ２ with a binaphthol which may have at least one of the following: The present invention relates to a method for producing an optically active compound having a binaphthol moiety represented by general formula (I).

2. The method for producing an optically active compound having a binaphthol moiety according to claim 1, wherein the nitrogen-containing basic compound is at least one selected from the group consisting of 4-dimethylaminopyridine, morpholine, pyridine, 1-naphthylamine, 4,4'-diaminodiphenyl ether, N-methylimidazole, tributylamine, N,N-dimethylaniline, N,N-diethylaniline, and aniline.

3. The method for producing an optically active compound having a binaphthol moiety according to claim 1 or 2, wherein the nitrogen-containing basic compound is used in an amount of 0.1 mol to 1.5 mol per 1 mol of the compound represented by general formula (III).

4. 3. The method for producing an optically active compound having a binaphthol moiety according to claim 1 or 2, wherein the protecting group in the compound represented by general formula (III) is at least one selected from the group consisting of an ethoxymethyl group, a methoxymethyl group, a methoxyethoxymethyl group, a benzyloxymethyl group, a tetrahydropyranyl group, a 2,2,2-trichloroethyl group, an alkyl group having 1 to 4 carbon atoms, a benzyl group, and a triphenylmethyl group.

5. The following general formula (III): 【Chemistry 7】 (In the formula, PG represents a protecting group, A １ represents the same meaning as above.) and a nitrogen-containing basic compound having a pKa of 4 to 10.

6. The deprotection inhibiting intermediate composition according to claim 5, wherein the nitrogen-containing basic compound is at least one selected from the group consisting of 4-dimethylaminopyridine, morpholine, pyridine, 1-naphthylamine, 4,4'-diaminodiphenyl ether, N-methylimidazole, tributylamine, N,N-dimethylaniline, N,N-diethylaniline, and aniline.

7. The deprotection inhibiting intermediate composition according to claim 5 or 6, wherein the nitrogen-containing basic compound is contained in an amount of 0.1 mol to 1.5 mol per 1 mol of the compound represented by general formula (III).

8. The intermediate composition for inhibiting deprotection according to claim 5 or 6, wherein the protecting group in the compound represented by general formula (III) is at least one selected from the group consisting of an ethoxymethyl group, a methoxymethyl group, a methoxyethoxymethyl group, a benzyloxymethyl group, a tetrahydropyranyl group, a 2,2,2-trichloroethyl group, an alkyl group having 1 to 4 carbon atoms, a benzyl group, and a triphenylmethyl group.

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