4-Alkylidene-1,3-dioxan-5-one and its manufacturing method

Abstract

The present invention relates to a method for producing a compound represented by the following formula (I), which comprises a step of subjecting a compound represented by the following formula (II) and a compound represented by the following formula (III) to an aldol condensation reaction in the presence of [1] a compound represented by the following formula (I) and [2] a compound represented by the following formula (IV): TIFF0007773005000076.tif1968 The present invention relates to [3] a method for producing a compound represented by the following formula (VI), which comprises a step of subjecting a compound represented by the following formula (V) to a reduction reaction together with an ammonia equivalent. TIFF0007773005000077.tif2144

Description

[Technical Field]

[0001] The present invention relates to 4-alkylidene-1,3-dioxan-5-ones and a method for producing the same. [Background technology]

[0002] Dioxanone derivatives, which are obtained by elongating the carbon chain through the aldol reaction or aldol condensation of 1,3-dioxan-5-one (hereinafter also referred to as "dioxanone") with an aldehyde, are useful as synthetic intermediates for chiral natural organic compounds such as sugars, sphingoid bases, and ceramides.

[0003] Canadian Journal of Chemistry, 73, 1616-1626, 1995 (Non-Patent Document 1) discloses an asymmetric aldol reaction in which a chiral enolate generated from a chiral lithium amide base and dioxanone is reacted with an aldehyde. Furthermore, Chemical Communications, 655-657, 2006 (Non-Patent Document 2) discloses an asymmetric aldol reaction between a ketone-type dioxanone and an aliphatic aldehyde using (S)-proline as a catalyst. Furthermore, Journal of the American Chemical Society, 130(51), 17287-17289, 2008 (Non-Patent Document 3) discloses an aldol condensation reaction between a ketone-type dioxanone and an aliphatic aldehyde using a complex of a highly branched polyalkyleneimine and proline as a catalyst. Furthermore, Heterocyclic Communications, 25, 85-90, 2019 (Non-Patent Document 4) discloses an aldol condensation reaction between an orthoester of 1,3-dihydroxyacetone and an aromatic aldehyde using pyrrolidine as a catalyst.

[0004] Regarding the production method of a dioxanone derivative having an elongated carbon chain, a method of elongating the carbon chain from the ketone moiety of dioxanone as a starting point has been investigated. For example, US Pat. No. 7,851,639 (Patent Document 1) discloses an aldol reaction between dioxanone and an aldehyde using proline or a proline derivative as a catalyst. Summary of the Invention

[0005] The present invention relates to a 4-alkylidene-1,3-dioxan-5-one represented by the following formula (I) and a method for producing the same. [ka] (In formula (I), R 1 represents a hydrogen atom or a hydrocarbon group, and R 2 represents a hydrogen atom or a linear alkyl group. DETAILED DESCRIPTION OF THE INVENTION

[0006] The methods of extending a carbon chain starting from the ketone moiety of dioxanone shown in Patent Document 1 and Non-Patent Documents 1 to 4 have actually only been carried out on 1,3-dioxan-5-ones having a ketal structure as part of their ring structure (hereinafter also referred to as "ketone-type dioxanones"). As far as the inventors know, there have been no examples of actually extending a carbon chain starting from the ketone moiety of 1,3-dioxan-5-ones having an acetal structure derived from an aliphatic aldehyde as part of their ring structure (hereinafter also referred to as "aldehyde-type dioxanones") to produce a 4-alkylidene-1,3-dioxan-5-one represented by formula (I).

[0007] The reason for this is not clear, but for example, Non-Patent Document 1 describes that in the enolate formation of dioxanone using a strong lithium amide base such as lithium diisopropylamide and the aldol reaction of the enolate with an aldehyde, the target product was obtained in a moderate yield in the reaction using a ketone dioxanone, but the target product was not obtained in the reaction using an aldehyde dioxanone. The reason given for this is that aldehyde dioxanone is less stable than ketone dioxanone and has the characteristic of being more susceptible to carbonyl group reduction and self-aldol reaction. The present invention relates to a 4-alkylidene-1,3-dioxan-5-one and a method for producing the same using an aldehyde-type dioxanone as a raw material.

[0008] The present invention relates to the following [1] to [5]. [1] 4-Alkylidene-1,3-dioxane-5-one represented by the following formula (I): [ka] (In formula (I), R 1 represents a hydrogen atom or a hydrocarbon group, and R 2 represents a hydrogen atom or a linear alkyl group. [2] A method for producing a compound represented by the following formula (I), comprising a step of subjecting a compound represented by the following formula (II) and a compound represented by the following formula (III) to an aldol condensation reaction in the presence of a compound represented by the following formula (IV): [ka] (In formula (I), formula (II), formula (III), and formula (IV), R 1 represents a hydrogen atom or a hydrocarbon group, and R 2 represents a hydrogen atom or a linear alkyl group. 3 , R 4 , and R 5 each independently represents a group selected from a hydrogen atom, a hydroxyl group, an alkoxy group, an N,N-dialkylamino group, an alkoxymethyl group, an N,N-dialkylaminomethyl group, a carboxy group, a carbamoyl group, an acyloxy group, an acylamino group, a silyloxy group, an alkoxycarbonyloxy group, and an alkoxycarbonylamino group. [3] A method for producing a compound represented by the following formula (VI), comprising a step of subjecting a compound represented by the following formula (V) to a reduction reaction together with an ammonia equivalent: [ka] (In formula (V) and formula (VI), R 1represents a hydrogen atom or a hydrocarbon group, and R 2 represents a hydrogen atom or a linear alkyl group. 6 represents a hydrogen atom or a substituted or unsubstituted arylmethyl group. [4] A method for producing a compound represented by the following formula (VII) from the compound represented by formula (VI) obtained by the production method according to [3], A method comprising a step of subjecting the compound represented by formula (VI) above and a compound represented by formula (VIII) below to an amidation reaction: [ka] (In formula (VII), R 1 represents a hydrogen atom or a hydrocarbon group, and R 2 represents a hydrogen atom or a linear alkyl group, and R 6 represents a hydrogen atom or a substituted or unsubstituted arylmethyl group. 7 represents a linear alkyl group having 1 to 29 carbon atoms. In formula (VIII), X represents a hydroxyl group, an alkoxy group, an alkylcarbonyloxy group, or a halogen atom. [5] A method for producing a compound represented by formula (IX), comprising: A method comprising a step of subjecting at least one compound selected from the compound represented by formula (VI) produced by the method according to [3] and the compound represented by formula (VII) produced by the method according to [4] to a deacetalization reaction. [ka] (In formula (VI) and formula (VII), R 1 represents a hydrogen atom or a hydrocarbon group, and R 6 represents a hydrogen atom or a substituted or unsubstituted arylmethyl group. 2 represents a hydrogen atom or a linear alkyl group. 7 represents a linear alkyl group having 1 to 29 carbon atoms. 8represents a hydrogen atom, a substituted or unsubstituted arylmethyl group, or a linear acyl group having from 1 to 30 carbon atoms.

[0009] According to the present invention, it is possible to provide 4-alkylidene-1,3-dioxan-5-one, which is useful as a synthetic intermediate for various compounds such as sphingoid bases and ceramides, and a method for producing 4-alkylidene-1,3-dioxan-5-one using an aldehyde-type dioxanone as a raw material.

[0010] [Compound represented by formula (I)] The compound represented by the following formula (I) is 4-alkylidene-1,3-dioxane-5-one.

[0011] [ka]

[0012] In formula (I), R 1 represents a hydrogen atom or a hydrocarbon group, and R 2 represents a hydrogen atom or a linear alkyl group. In addition, in formula (I), a bond represented by a wavy line represents that the compound represented by formula (I) is an (E) or (Z) isomer, or a mixture of the (E) and (Z) isomers.

[0013] R 1Examples of the hydrocarbon group as the alkyl group include an alkyl group, an alkenyl group, an alkynyl group, and an aromatic group. From the viewpoint of the stability of the acetal moiety under acidic conditions, a group selected from an alkyl group, an alkenyl group, and an alkynyl group is preferred. From the viewpoint of the usefulness of the compound represented by formula (I) as a synthetic intermediate for producing a sphingoid base, a ceramide, or the like (hereinafter also referred to as "usefulness of the compound represented by formula (I) as a synthetic intermediate"), an alkyl group is more preferred. The alkyl group may be any of a linear alkyl group, a branched alkyl group, and a cyclic alkyl group, and examples thereof include a methyl group, an ethyl group, an n-propyl group, an isopropyl group, a cyclopropyl group, an n-butyl group, an s-butyl group, a t-butyl group, an isobutyl group, a cyclobutyl group, an n-pentyl group, an isopentyl group, a neopentyl group, a cyclopentyl group, a hexyl group, a cyclohexyl group, a heptyl group, an octyl group, a nonyl group, and a decyl group. R 1 The hydrocarbon group may be substituted with an aromatic group such as a phenyl group, a naphthyl group, etc. For example, alkyl groups substituted with an aromatic group include a phenylmethyl group, a phenylethyl group, a naphthylmethyl group, and a naphthylethyl group. R 1 The aromatic group as may be substituted with a hydrocarbon group such as an alkyl group, an alkenyl group, an alkynyl group, etc. For example, aromatic groups substituted with an alkyl group include a methylphenyl group, an ethylphenyl group, a methylnaphthyl group, an ethylnaphthyl group, etc., and aromatic groups substituted with an alkenyl group include a vinylphenyl group, a vinylnaphthyl group, etc.

[0014] R 1 From the viewpoint of usefulness as a synthetic intermediate of the compound represented by formula (I), is preferably an alkyl group having 1 to 8 carbon atoms, more preferably an alkyl group having 1 to 4 carbon atoms, and even more preferably a methyl group or an ethyl group.

[0015] R 2 The alkyl group as the alkyl group may be a straight-chain alkyl group, and examples thereof include alkyl groups having 1 to 21 carbon atoms.

[0016] R 2 From the viewpoint of usefulness as a synthetic intermediate of the compound represented by formula (I), is preferably a hydrogen atom or a linear alkyl group having from 1 to 21 carbon atoms, more preferably a linear alkyl group having from 8 to 18 carbon atoms, and even more preferably an n-tetradecyl group.

[0017] R 1 and R 2 is preferably a combination of R 1 is an alkyl group having 1 to 8 carbon atoms, R 2 is a hydrogen atom or a linear alkyl group having 1 to 21 carbon atoms, more preferably R 1 is an alkyl group having 1 to 4 carbon atoms, R 2 is a linear alkyl group having 8 to 18 carbon atoms, more preferably R 1 is an alkyl group having 1 to 4 carbon atoms, R 2 is an n-tetradecyl group, and even more preferably R 1 is a methyl group or an ethyl group, R 2 is an n-tetradecyl group.

[0018] [Method for producing the compound represented by formula (I)] A method for producing a compound represented by the following formula (I) includes a step of subjecting a compound represented by the following formula (II) and a compound represented by the following formula (III) to an aldol condensation reaction in the presence of a compound represented by the following formula (IV).

[0019] [ka]

[0020] In formulas (I) to (III), R 1 represents a hydrogen atom or a hydrocarbon group, and R 2 represents a hydrogen atom or a linear alkyl group. In formula (IV), R 3 , R 4 , and R 5each independently represents a group selected from a hydrogen atom, a hydroxyl group, an alkoxy group, an N,N-dialkylamino group, an alkoxymethyl group, an N,N-dialkylaminomethyl group, a carboxy group, a carbamoyl group, an acyloxy group, an acylamino group, a silyloxy group, an alkoxycarbonyloxy group, and an alkoxycarbonylamino group.

[0021] (Compound represented by formula (II)) The compound represented by the following formula (II) is an aldehyde-type 1,3-dioxane-5-one.

[0022] [ka]

[0023] In formula (II), R 1 is R in formula (I) 1 In formula (II), R 1 The hydrocarbon group and its preferred range are as follows: R 1 is the same as:

[0024] Although there is no limitation on the method for producing the compound represented by formula (II), from the viewpoint of inexpensive and easy acquisition of dioxanone, the method for producing the compound represented by formula (II) is preferably the method described in Japanese Patent No. 6405443 (Patent Document 2) using glycerin and an aldehyde as raw materials. This patent publication discloses a method for producing 1,3-dioxan-5-one, which includes a step of oxidizing a mixture of 5-hydroxy-1,3-dioxane and 4-hydroxymethyl-1,3-dioxolane (obtained from glycerin and an aldehyde as raw materials) under oxidative esterification conditions.

[0025] (Compound represented by formula (III)) The compound represented by the following formula (III) is an aliphatic aldehyde.

[0026] [ka]

[0027] In formula (III), R 2 is R in formula (I) 2 In formula (III), R 2 The linear alkyl group as R in formula (I) and its preferred range are as follows: 2 is the same as:

[0028] In the production method of the present invention, the compound represented by formula (III) may be a commercially available product or may be produced by a generally known method. Although there is no limitation on the production method of the compound represented by formula (III), the production method of the compound represented by formula (III) is preferably produced by oxidation of an alcohol or hydroformylation of an α-olefin, from the viewpoint of inexpensive and easy availability of the compound represented by formula (III).

[0029] (Compound represented by formula (IV)) The compound represented by formula (IV) is pyrrolidine or a derivative thereof.

[0030] [ka]

[0031] R 3 , R 4 and R 5 The alkoxy group as may be either a group in which a linear alkyl group is bonded to oxygen or a group in which a branched alkyl group is bonded to oxygen, and examples of the linear alkyl group and the branched alkyl group include a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an s-butyl group, and a t-butyl group. R 3 , R 4 and R 5The N,N-dialkylamino group as the N,N-dialkylamino group is a group in which two of a linear alkyl group and a branched alkyl group are bonded to a nitrogen atom, and examples of the linear alkyl group and the branched alkyl group include a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an s-butyl group, a t-butyl group, etc. In addition, the linear alkyl group and / or the branched alkyl group bonded to the nitrogen atom of the N,N-dialkylamino group may be bonded to form a nitrogen-containing aliphatic ring. R 3 , R 4 and R 5 The alkoxy group of the alkoxymethyl group as mentioned above includes those exemplified above as the alkoxy group. R 3 , R 4 and R 5 As the N,N-dialkylamino group of the N,N-dialkylaminomethyl group as the aryl group, those exemplified above for the N,N-dialkylamino group can be mentioned. R 3 , R 4 and R 5 Examples of the acyl group in the acyloxy group as mentioned above include a formyl group, an acetyl group, a propionyl group, a butyryl group, an isobutyryl group, a pentanoyl group, and a pivaloyl group. R 3 , R 4 and R 5 Examples of the acyl group in the acylamino group include those exemplified above for the acyloxy group. R 3 , R 4 and R 5 The silyloxy group as defined above is a group in which a silyl group is bonded to an oxygen atom, and in this specification, the silyl group refers to a group in which any three selected from a hydrogen atom, an alkyl group, an alkenyl group, and an aromatic group are substituted on a silicon atom. Examples of the alkyl group contained in the silyl group include a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an s-butyl group, and a t-butyl group. Examples of the alkenyl group contained in the silyl group include a vinyl group and an allyl group. Examples of the aromatic group contained in the silyl group include a phenyl group and a tolyl group. R 3 , R 4 and R 5 The alkoxy group of the alkoxycarbonyloxy group as mentioned above includes those exemplified above as the alkoxy group. R 3 , R 4 and R 5 The alkoxy group of the alkoxycarbonylamino group as mentioned above includes those exemplified above as the alkoxy group.

[0032] R 3 From the viewpoint of ease of availability or preparation of the compound represented by formula (IV), R is preferably at least one selected from a hydrogen atom and a carboxy group, and more preferably a hydrogen atom. 4 and R 5 From the viewpoint of improving the production efficiency of the compound represented by formula (I), is preferably at least one selected from a hydroxyl group, an alkoxy group, an N,N-dialkylamino group, an alkoxymethyl group, an N,N-dialkylaminomethyl group, a carboxy group, a carbamoyl group, an acyloxy group, an acylamino group, an alkoxycarbonyloxy group, and an alkoxycarbonylamino group, and more preferably at least one selected from a hydroxyl group, an alkoxy group, an N,N-dialkylamino group, an acylamino group, an alkoxycarbonyloxy group, and an alkoxycarbonylamino group.

[0033] In the method for producing the compound represented by formula (I), R 1A compound represented by formula (I) is enantioselectively obtained by subjecting a compound represented by formula (II), in which ⁢ ⁢ ⁢ ⁢ ⁢ ⁢ (III), in the presence of a compound represented by formula (IV) having an enantiomeric excess of 90% ee, to an aldol condensation reaction. Naturally occurring compounds such as sphingoid bases and ceramides have a single enantiomer or a high enantiomeric excess, and therefore their production is preferably carried out enantioselectively. Therefore, a compound represented by formula (I) produced enantioselectively can be used as a useful synthetic intermediate for various compounds, from the viewpoint of minimizing product loss due to enantiomer separation. The enantiomeric excess of a compound represented by formula (IV) can be determined by the manufacturer's specifications when using a commercially available product, or by liquid chromatography using a chiral column when producing the compound.

[0034] The absolute configuration of the enantioselectively produced compound represented by formula (I) can be determined by obtaining a compound represented by formula (V) described below from the compound represented by formula (I), and then determining the absolute configuration of the compound represented by formula (V) or a derivative of the compound represented by formula (V) by a known method for determining the absolute configuration. For example, as described below, the absolute configuration of the compound represented by formula (I) may be determined by preparing a sphingoid base or ceramide from the compound represented by formula (I), and directly or indirectly comparing the prepared sphingoid base or ceramide with a sphingoid base or ceramide of known absolute configuration.

[0035] In the method for producing the compound represented by formula (I), from the viewpoint of usefulness as a synthetic intermediate of the compound represented by formula (I), R 1 is preferably an alkyl group having 1 to 8 carbon atoms, more preferably a methyl group or an ethyl group, and R 2 is preferably an n-tetradecyl group, and in the compound represented by formula (IV), R 3 is preferably a hydrogen atom, and R 4 and R 5is preferably at least one selected from a hydroxyl group, an alkoxy group, an N,N-dialkylamino group, an acylamino group, an alkoxycarbonyloxy group, and an alkoxycarbonylamino group.

[0036] Specific examples of the compound represented by formula (IV) include pyrrolidine, proline, prolinamide, trans-4-(tert-butyldiphenylsilyloxy)-proline, 2-(methoxymethyl)pyrrolidine, 1-(2-pyrrolidinylmethyl)pyrrolidine, 3-pyrrolidinol, 3,4-pyrrolidinediol, 3-(dimethylamino)pyrrolidine, acetamidopyrrolidine, 3-(tert-butoxycarbonyloxy)pyrrolidine, and 3-(tert-butoxycarbonylamino)pyrrolidine.

[0037] From the viewpoint of obtaining the compound represented by formula (I) in high yield and with high enantioselectivity, the compound represented by formula (IV) is preferably at least one selected from proline, 3-pyrrolidinol, 3,4-pyrrolidinediol, 3-acetamidopyrrolidine, and 3-(tert-butoxycarbonylamino)pyrrolidine, more preferably at least one selected from 3-pyrrolidinol and 3,4-pyrrolidinediol.

[0038] In the method for producing the compound represented by formula (I), the amount of the compound represented by formula (II) used is preferably in a molar ratio to the compound represented by formula (III) (compound represented by formula (II) / compound represented by formula (III)) of 1.0 or more, from the viewpoint of suppressing the formation of an aldol condensation product consisting of two molecules of the compound represented by formula (III), by-products in which the compound represented by formula (III) is condensed at the 4- and 6-positions of the compound represented by formula (II), etc. Furthermore, from the viewpoint of improving production efficiency, the molar ratio is preferably 3.5 or less.

[0039] In the method for producing a compound represented by formula (I), the amount of the compound represented by formula (IV) used relative to the compound represented by formula (III) is preferably 0.1 or more, more preferably 0.15 or more, and even more preferably 0.2 or more, in terms of increasing the reactivity of the aldol condensation reaction, as a molar ratio (compound represented by formula (IV) / compound represented by formula (III)). From the same viewpoint, the molar ratio is preferably 1.5 or less, more preferably 1.2 or less, and even more preferably 1.1 or less. The molar ratio (compound represented by formula (IV) / compound represented by formula (III)) is preferably 0.1 or more and 1.5 or less, more preferably 0.15 or more and 1.2 or less, and even more preferably 0.2 or more and 1.1 or less.

[0040] In the method for producing the compound represented by formula (I), the aldol condensation reaction may be carried out in the presence or absence of a solvent. From the viewpoint of reducing the viscosity of the reaction system of the aldol condensation reaction to facilitate stirring and from the viewpoint of the workability of post-reaction treatment, the aldol condensation reaction is preferably carried out in the presence of a solvent. In this specification, the expression "carrying out the reaction in the absence of a solvent" means that the reaction is carried out in the absence of a medium normally used as a solvent, excluding compounds described as being related to the reaction. The aldol condensation reaction can be carried out in the presence of a solvent that promotes the aldol condensation reaction. From the viewpoint of improving the production efficiency of the compound represented by formula (I), the solvent is preferably selected from alcohols, ethers, alkyl halides, nitriles, and hydrocarbons, more preferably selected from methyl tert-butyl ether, ethyl tert-butyl ether, cyclopentyl methyl ether, chloroform, diethylene glycol monoethyl ether, 2-propanol, dichloromethane, acetonitrile, toluene, octane, and hexane, and even more preferably selected from methyl tert-butyl ether, ethyl tert-butyl ether, and cyclopentyl methyl ether.

[0041] In the method for producing the compound represented by formula (I), from the viewpoint of improving the production efficiency of the compound represented by formula (I), the aldol condensation reaction is preferably carried out in the presence of a carboxylic acid. When the compound represented by formula (IV) has low solubility in the organic solvent, the compound represented by formula (IV) can be dissolved in the reaction system by adding a carboxylic acid, thereby improving the production efficiency of the compound represented by formula (I). Furthermore, even when a compound represented by formula (IV) that is soluble in various organic solvents is used, the aldol condensation reaction is preferably carried out in the presence of a carboxylic acid, since this improves the production efficiency of the compound represented by formula (I).

[0042] Examples of the carboxylic acid include aliphatic monocarboxylic acids such as formic acid, acetic acid, propionic acid, butanoic acid, pentanoic acid, hexanoic acid, heptanoic acid, and octanoic acid; aliphatic dicarboxylic acids such as oxalic acid, malonic acid, and succinic acid; aromatic monocarboxylic acids such as benzoic acid; and aromatic dicarboxylic acids such as phthalic acid. From the viewpoint of improving the production efficiency of the compound represented by formula (I), the carboxylic acid is preferably an aliphatic monocarboxylic acid, more preferably formic acid, acetic acid, and propionic acid, and even more preferably acetic acid.

[0043] When the aldol condensation reaction is carried out in the presence of a carboxylic acid, the amount of the carboxylic acid used relative to the compound represented by formula (III) is preferably greater than 0, more preferably greater than 1.0, and even more preferably greater than 3.0, in terms of improving production efficiency (carboxylic acid / compound represented by formula (III)). From the same viewpoint, the molar ratio is preferably 70 or less, more preferably 60 or less, and even more preferably 50 or less. The molar ratio (carboxylic acid / compound represented by formula (III)) is preferably greater than 0 and less than 70, more preferably 1.0 or more and 60 or less, and even more preferably 3.0 or more and 50 or less.

[0044] In the aldol condensation reaction, there is no limitation on the order in which the raw materials are charged, etc. However, from the viewpoint of suppressing the production of a by-product resulting from the aldol condensation of two molecules of the compound represented by formula (III) with the compound represented by formula (II), the order in which the raw materials are charged is preferably such that the compound represented by formula (IV) is added to a mixture of raw materials other than the compound represented by formula (IV).

[0045] From the viewpoint of selectively obtaining the compound represented by formula (I), the reaction temperature of the aldol condensation reaction is preferably 0° C. or higher, more preferably 10° C. or higher, and even more preferably 15° C. or higher. From the same viewpoint, the reaction temperature is preferably 50° C. or lower, more preferably 40° C. or lower, and even more preferably 30° C. or lower. The reaction temperature of the aldol condensation reaction is preferably 0° C. or higher and 50° C. or lower, more preferably 10° C. or higher and 40° C. or lower, and even more preferably 15° C. or higher and 30° C. or lower. The aldol condensation reaction is preferably stopped by adding water or an aqueous solution of an inorganic salt to the reaction system and stirring. The reaction may be considered complete when the amount of the compound represented by formula (I) is confirmed every 1 to 2 hours using gas chromatography, liquid chromatography, or the like, and the increase in the amount of the compound represented by formula (I) stops or becomes small. Examples of inorganic salts include sodium chloride, ammonium chloride, and sodium sulfate. After the reaction is complete, the compound represented by formula (IV) can be recovered and reused.

[0046] [Method for producing the compound represented by formula (VI)] A compound represented by the following formula (VI) can be produced by a method comprising a step of subjecting a compound represented by formula (V) to a reduction reaction together with an ammonia equivalent.

[0047] [ka]

[0048] In formula (VI), R 1 and R 2 is R in formula (I). 1 and R 2is synonymous with R 6 represents a hydrogen atom or a substituted or unsubstituted arylmethyl group. 1 Hydrocarbon group as R 2 The linear alkyl groups as R in formula (I) and their preferred ranges are as follows: 1 and R 2 is the same as:

[0049] R 6 Examples of the arylmethyl group include a benzyl group and a naphthylmethyl group, with a benzyl group being preferred. The substituent of the arylmethyl group is preferably an aryl group, with examples including an alkyl group, a hydroxyl group, an alkoxy group, and a halogen atom. The alkyl group and alkoxy group as the substituent may further be substituted with a halogen atom.

[0050] It is believed that the compound represented by formula (VI) can be obtained by reducing the carbon-nitrogen double bond of the imine and / or iminium cation generated by dehydration condensation of the compound represented by formula (V) and the ammonia equivalent with a reducing agent, so-called reductive amination.

[0051] (ammonia equivalent) Examples of the ammonia equivalent used in the reduction reaction include ammonia; ammonium salts of carboxylic acids such as ammonium formate, ammonium acetate, and ammonium trifluoroacetate; substituted or unsubstituted arylmethylamines such as benzylamine; and disilazanes such as 1,1,1,3,3,3-hexamethyldisilazane (hereinafter also referred to as "hexamethyldisilazane"). When ammonia, ammonium salts of carboxylic acids, and disilazanes are used as the ammonia equivalent, R 6 is a hydrogen atom, and when a substituted or unsubstituted arylmethylamine is used as the ammonia equivalent, R 6 is a hydrogen atom or a substituted or unsubstituted arylmethyl group, From the viewpoint of improving production efficiency, the ammonia equivalent is preferably at least one selected from an ammonium salt of a carboxylic acid, a substituted or unsubstituted arylmethylamine, and hexamethyldisilazane, and more preferably at least one selected from ammonium formate, ammonium acetate, ammonium trifluoroacetate, a substituted or unsubstituted arylmethylamine, and hexamethyldisilazane. When ammonium formate is used as the ammonium equivalent, there is no need to add hydrogen gas as a reducing agent when the reduction reaction is carried out in the presence of a transition metal catalyst, which is preferable from the viewpoint of safety of the production method.

[0052] In the method for producing the compound represented by formula (VI), the amount of ammonia equivalent used may vary depending on the compound used. When ammonia or an ammonium salt of a carboxylic acid is used as the ammonia equivalent, the molar ratio of the amount of the ammonia equivalent to the compound represented by formula (V) (ammonia equivalent / compound represented by formula (V)) is preferably 1 or more, more preferably 3 or more, and even more preferably 5 or more, from the viewpoint of improving production efficiency. Also, from the same viewpoint, the molar ratio is preferably 20 or less, more preferably 15 or less, and even more preferably 12 or less. When ammonia or an ammonium salt of a carboxylic acid is used as the ammonia equivalent, the molar ratio (ammonia equivalent / compound represented by formula (V)) is preferably 1 or more and 20 or less, more preferably 3 or more and 15 or less, and even more preferably 5 or more and 12 or less. When a substituted or unsubstituted arylmethylamine or disilazane is used as the ammonia equivalent, the molar ratio of the amount of ammonia equivalent to the compound represented by formula (V) (ammonia equivalent / compound represented by formula (V)) is preferably 0.8 or more, more preferably 0.9 or more, and even more preferably 1 or more, from the viewpoint of improving production efficiency. Also, from the same viewpoint, the molar ratio is preferably 10 or less, more preferably 5 or less, and even more preferably 3 or less. When a substituted or unsubstituted arylmethylamine or disilazane is used as the ammonia equivalent, the molar ratio (ammonia equivalent / compound represented by formula (V)) is preferably 0.8 or more and 10 or less, more preferably 0.9 or more and 5 or less, and even more preferably 1 or more and 3 or less.

[0053] In the method for producing the compound represented by formula (VI), from the viewpoint of availability of raw materials and improvement of production efficiency, R 1 is preferably an alkyl group having 1 to 8 carbon atoms, more preferably a methyl group or an ethyl group, and R 2 is preferably an n-tetradecyl group, and the ammonia equivalent is preferably at least one selected from the group consisting of ammonium formate, ammonium acetate, ammonium trifluoroacetate, substituted or unsubstituted arylmethylamine, and hexamethyldisilazane.

[0054] (reducing agent) The reduction reaction can be carried out in the presence of any reducing agent capable of reducing the carbon-nitrogen double bond of the imine intermediate and the iminium cation intermediate. Examples of the reducing agent include hydrogen; formic acid derivatives such as formic acid, alkali metal formic acid salts such as sodium formate, and amine formic acid salts such as ammonium formate; ate complex-type hydride reducing agents such as sodium borohydride, sodium triacetoxyborohydride, and sodium cyanoborohydride (excluding the following compounds in which an unpaired electron pair of an organic compound is coordinated to borane); and complexes in which an unpaired electron pair of an organic compound is coordinated to borane (BH3) such as tetrahydrofuran borane complex, dimethylsulfide borane complex, pyridine borane complex, 2-picoline borane complex, and 5-ethyl-2-methylpyridine borane complex (hereinafter simply referred to as "borane").

[0055] When the reduction reaction is carried out in the presence of hydrogen or ammonium formate, it is preferable to carry out the reduction reaction in the presence of a transition metal catalyst from the viewpoint of improving production efficiency. Any transition metal catalyst active in hydrogenating the carbon-nitrogen double bond of the imine intermediate and the iminium cation intermediate can be used as the transition metal catalyst. From the viewpoint of ease of separation and recovery of the transition metal catalyst, the transition metal catalyst is preferably at least one selected from a catalyst in which a platinum group element and / or its hydroxide is supported on a carrier, and a sponge metal catalyst, more preferably at least one selected from a palladium-carbon catalyst, a palladium hydroxide-carbon catalyst, and a sponge nickel catalyst, and even more preferably at least one selected from a palladium-carbon catalyst and a palladium hydroxide-carbon catalyst. Regarding the amount of transition metal catalyst used, from the viewpoint of improving production efficiency, the molar ratio of the active metal species in the transition metal catalyst to the compound represented by formula (V) (active metal species in transition metal catalyst / compound represented by formula (V)) is preferably 0.001 or more, more preferably 0.005 or more, and even more preferably 0.01 or more. From the same viewpoint, the molar ratio is preferably 0.2 or less, more preferably 0.1 or less, and even more preferably 0.05 or less. The molar ratio (active metal species in transition metal catalyst / compound represented by formula (V)) is preferably 0.001 or more and 0.2 or less, more preferably 0.005 or more and 0.1 or less, and even more preferably 0.01 or more and 0.05 or less.

[0056] When the reduction reaction is carried out in the presence of a transition metal catalyst or an ate complex type hydride reducing agent, the compound represented by formula (VI) ((4R * ,5R * )-4-alkyl-5-amino-1,3-dioxane) can be obtained. * and S * indicates relative placement. When the compound represented by formula (VI) is obtained selectively with 4,5-syn, from the viewpoint of improving production efficiency, the reducing agent is preferably hydrogen or ammonium formate when the reduction reaction is carried out in the presence of a transition metal catalyst, and is preferably sodium triacetoxyborohydride when the reduction reaction is carried out in the presence of an ate complex-type hydride reducing agent.

[0057] Furthermore, when the reduction reaction is carried out in the presence of borane, the compound represented by formula (I) ((4R * ,5S * )-4-Alkyl-5-amino-1,3-dioxane) can be obtained. When the compound represented by formula (I) is obtained in a 4,5-anti-selective manner, the reducing agent is preferably at least one selected from 2-picoline borane complex and 5-ethyl-2-methylpyridine borane complex, more preferably 2-picoline borane complex, from the viewpoint of improving production efficiency.

[0058] The amount of reducing agent used may vary depending on the reducing agent used. When the reduction reaction is carried out in the presence of hydrogen gas, there are no limitations on the hydrogen pressure. However, from the viewpoint of improving production efficiency, the hydrogen pressure of the hydrogen gas introduced into the reaction system is preferably atmospheric pressure (gauge pressure 0 MPa) or higher, more preferably 0.05 MPa or higher, and even more preferably 0.1 MPa or higher. Furthermore, from the viewpoint of functional group selectivity and equipment load, the hydrogen pressure is preferably 2.0 MPa or lower, more preferably 1.0 MPa or lower, and even more preferably 0.5 MPa or lower. The hydrogen pressure of the hydrogen gas introduced into the reaction system is preferably atmospheric pressure (gauge pressure 0 MPa) or higher and 2.0 MPa or lower, more preferably 0.05 MPa or higher and 1.0 MPa or lower, and even more preferably 0.1 MPa or higher and 0.5 MPa or lower. When the reduction reaction is carried out in the presence of ammonium formate, from the viewpoint of improving production efficiency, the molar ratio of ammonium formate to the compound represented by formula (V) (ammonium formate / compound represented by formula (V)) is preferably 1 or more, more preferably 3 or more, and even more preferably 5 or more. From the same viewpoint, the molar ratio is preferably 20 or less, more preferably 15 or less, and even more preferably 12 or less. The molar ratio (ammonium formate / compound represented by formula (V)) is preferably 1 or more and 20 or less, more preferably 3 or more and 15 or less, and even more preferably 5 or more and 12 or less. When the reduction reaction is carried out in the presence of an ate complex hydride reducing agent, the molar ratio of hydride ions in the ate complex hydride reducing agent to the compound represented by Formula (V) (hydride ions in the ate complex hydride reducing agent / compound represented by Formula (V)) is preferably 1.0 or more, more preferably 1.2 or more, and even more preferably 1.4 or more, from the viewpoint of improving production efficiency. From the same viewpoint, the molar ratio is preferably 10 or less, more preferably 5 or less, and even more preferably 3 or less. Furthermore, the molar ratio (hydride ions in the ate complex hydride reducing agent / compound represented by Formula (V)) is preferably 1.0 or more and 10 or less, more preferably 1.2 or more and 5 or less, and even more preferably 1.4 or more and 3 or less. When the reduction reaction is carried out in the presence of borane, from the viewpoint of improving production efficiency, the molar ratio of borane to the compound represented by formula (V) (borane / compound represented by formula (V)) is preferably 0.3 or more, more preferably 0.4 or more, and even more preferably 0.5 or more. From the same viewpoint, the molar ratio is preferably 5 or less, more preferably 3 or less, and even more preferably 2.5 or less. The molar ratio (borane / compound represented by formula (V)) is preferably 0.3 or more and 5 or less, more preferably 0.4 or more and 3 or less, and even more preferably 0.5 or more and 2.5 or less.

[0059] The reduction reaction is preferably carried out in the presence of an acid, from the viewpoint of improving production efficiency. The acid is preferably at least one selected from Lewis acids and carboxylic acids having from 1 to 6 carbon atoms, more preferably at least one selected from scandium trifluoromethanesulfonate (scandium triflate), formic acid, acetic acid, and propionic acid, and even more preferably at least one selected from scandium trifluoromethanesulfonate and acetic acid.

[0060] The amount of acid used may vary depending on the acid used. When a Lewis acid is used as the acid, from the viewpoint of improving production efficiency, the molar ratio of the Lewis acid to the compound represented by formula (V) (Lewis acid / compound represented by formula (V)) is preferably 0.001 or more, more preferably 0.05 or more, and even more preferably 0.01 or more. From the same viewpoint, the molar ratio is preferably 1 or less, more preferably 0.5 or less, and even more preferably 0.2 or less. The molar ratio (Lewis acid / compound represented by formula (V)) is preferably 0.001 or more and 1 or less, more preferably 0.05 or more and 0.5 or less, and even more preferably 0.01 or more and 0.2 or less. When a carboxylic acid is used as the acid, from the viewpoint of improving production efficiency, the molar ratio of the carboxylic acid to the compound represented by formula (V) (carboxylic acid / compound represented by formula (V)) is preferably 0.1 or more, more preferably 0.5 or more, and even more preferably 0.8 or more. From the same viewpoint, the molar ratio is preferably 30 or less, more preferably 20 or less, and even more preferably 10 or less. The molar ratio (carboxylic acid / compound represented by formula (V)) is preferably 0.1 or more and 30 or less, more preferably 0.5 or more and 20 or less, and even more preferably 0.8 or more and 10 or less.

[0061] The reduction reaction may be carried out in the presence or absence of a solvent. From the viewpoint of reducing the viscosity of the reaction system of the reduction reaction to facilitate stirring and facilitating filtration after the reaction, the reduction reaction is preferably carried out in the presence of a solvent. From the viewpoint of improving production efficiency, the solvent is preferably at least one selected from alcohol, ether, and alkyl halide, more preferably at least one selected from methanol, ethanol, 2-propanol, tetrahydrofuran, methyl tert-butyl ether, ethyl tert-butyl ether, cyclopentyl methyl ether, dichloromethane, 1,2-dichloroethane, and chloroform, and even more preferably at least one selected from methanol, ethanol, 2-propanol, tetrahydrofuran, methyl tert-butyl ether, ethyl tert-butyl ether, and cyclopentyl methyl ether. Two or more solvents may be used.

[0062] In the reduction reaction, there is no limitation on the order in which the raw materials are charged. However, from the viewpoint of suppressing the production of by-products, the order in which the raw materials are charged is preferably such that the reducing agent is added to a mixture of raw materials other than the reducing agent.

[0063] From the viewpoint of improving production efficiency, the reaction temperature of the reduction reaction is preferably 0°C or higher, more preferably 5°C or higher, and even more preferably 10°C or higher. From the same viewpoint, the reaction temperature is preferably 80°C or lower, more preferably 70°C or lower, and even more preferably 60°C or lower. The reaction temperature of the reduction reaction is preferably 0°C or higher and 80°C or lower, more preferably 5°C or higher and 70°C or lower, and even more preferably 10°C or higher and 60°C or lower.

[0064] The completion of the reduction reaction can be determined by confirming the presence of the compound represented by formula (V) in the reaction system. The compound represented by formula (V) can be confirmed, for example, by thin layer chromatography. Alternatively, the amount of the compound represented by formula (V) can be confirmed every 1 to 2 hours using gas chromatography, liquid chromatography, or the like, and the reaction can be considered complete when the decrease in the amount of the compound represented by formula (V) has stopped or has become smaller. Treatment after completion of the reduction reaction can be carried out in accordance with a conventional method. For example, when the reduction reaction is carried out in the presence of a transition metal catalyst, the treatment method after completion of the reduction reaction can be such that the transition metal catalyst is filtered off, a basic aqueous solution is added to adjust the pH of the aqueous phase to 10 or higher, and then the compound represented by formula (VI) can be extracted using an organic solvent. When the reduction reaction is carried out in the presence of an arylmethylamine as an ammonia equivalent, the catalyst may not be filtered off, and the treatment method described above may be carried out after the debenzylation reaction described below. For example, when the reduction reaction is carried out in the presence of an ate complex-type hydride reducing agent, the treatment method after completion of the reduction reaction can be such that a basic aqueous solution is added to adjust the pH of the aqueous phase to 10 or higher, and then the compound represented by formula (VI) can be extracted using an organic solvent. For example, when the reduction reaction is carried out in the presence of borane, the treatment method after completion of the reduction reaction can be such that an acidic aqueous solution is added to hydrolyze the borane, and then a basic aqueous solution is added to adjust the pH of the aqueous phase to 10 or higher, and the compound represented by formula (VI) can be extracted using an organic solvent.

[0065] The resulting crude product of the compound represented by formula (VI) may be used in the next step as it is, or may be purified by means of distillation or the like before being used in the next step.

[0066] [Production of Compound Represented by Formula (V)] The compound represented by formula (I) can be subjected to a hydrogenation reaction to obtain the compound represented by formula (V).

[0067] [ka]

[0068] In formula (V), R 1 and R 2 is R in formula (I). 1 and R 2 In formula (I), R 1 Hydrocarbon group as R 2 The linear alkyl group as R in formula (I) and its preferred range are as follows: 1 and R 2 is the same as:

[0069] The compound represented by formula (I) is preferably produced by the method described above in "[Method for producing the compound represented by formula (I)]".

[0070] <Hydrogenation reaction> In the present invention, the hydrogenation reaction is a reaction in which the carbon-carbon double bond of the compound represented by formula (I) is hydrogenated to form a carbon-carbon single bond. 1 is a hydrocarbon group, R 1 Since alkyldioxanones in which the configuration of the alkyl groups at the 4- and 5-positions is syn-related can be obtained with high diastereoselectivity, R 1 is preferably a hydrocarbon group.

[0071] (catalyst) The hydrogenation reaction can be carried out in the presence of any catalyst active in hydrogenating the carbon-carbon double bond of the compound represented by formula (I). From the viewpoint of improving production efficiency, the catalyst is preferably at least one selected from a catalyst in which a platinum group element and / or a hydroxide thereof is supported on a carrier and a sponge metal catalyst, more preferably at least one selected from a palladium-carbon catalyst, a palladium hydroxide-carbon catalyst, and a sponge nickel catalyst, and even more preferably at least one selected from a palladium-carbon catalyst and a palladium hydroxide-carbon catalyst. Regarding the amount of catalyst used, from the viewpoint of improving production efficiency, the molar ratio of the active metal species in the catalyst to the compound represented by formula (I) (active metal species in the catalyst / compound represented by formula (I)) is preferably 0.001 or more, more preferably 0.005 or more, and even more preferably 0.01 or more. From the same viewpoint, the molar ratio is preferably 0.2 or less, more preferably 0.1 or less, and even more preferably 0.05 or less. The molar ratio (active metal species in the catalyst / compound represented by formula (I)) is preferably 0.001 or more and 0.2 or less, more preferably 0.005 or more and 0.1 or less, and even more preferably 0.01 or more and 0.05 or less.

[0072] In the hydrogenation reaction, there is no limitation on the hydrogen pressure, but from the viewpoint of improving production efficiency, the hydrogen pressure is preferably atmospheric pressure or higher, more preferably a gauge pressure of 0.05 MPa or higher, and even more preferably a gauge pressure of 0.1 MPa or higher. Furthermore, from the viewpoint of functional group selectivity and equipment load, the hydrogen pressure is preferably a gauge pressure of 2.0 MPa or lower, more preferably a gauge pressure of 1.0 MPa or lower, and even more preferably a gauge pressure of 0.5 MPa or lower. The hydrogen pressure is preferably atmospheric pressure or higher and a gauge pressure of 2.0 MPa or lower, more preferably a gauge pressure of 0.05 MPa or higher and a gauge pressure of 1.0 MPa or lower, and even more preferably a gauge pressure of 0.1 MPa or higher and a gauge pressure of 0.5 MPa or lower.

[0073] The hydrogenation reaction may be carried out in the presence or absence of a solvent. From the viewpoint of reducing the viscosity of the reaction system of the hydrogenation reaction and facilitating stirring, the reaction is preferably carried out in the presence of a solvent. From the viewpoint of improving production efficiency, the solvent is preferably at least one selected from alcohols, ethers, esters, and alkyl halides, more preferably at least one selected from methanol, ethanol, 2-propanol, tetrahydrofuran, methyl tert-butyl ether, ethyl tert-butyl ether, cyclopentyl methyl ether, ethyl acetate, dichloromethane, 1,2-dichloroethane, and chloroform, and even more preferably at least one selected from methanol, ethanol, 2-propanol, tetrahydrofuran, methyl tert-butyl ether, ethyl tert-butyl ether, cyclopentyl methyl ether, and ethyl acetate.

[0074] From the viewpoint of improving production efficiency, the reaction temperature of the hydrogenation reaction is preferably 0°C or higher, more preferably 5°C or higher, and even more preferably 10°C or higher. From the same viewpoint, the reaction temperature is preferably 80°C or lower, more preferably 70°C or lower, and even more preferably 60°C or lower. The reaction temperature of the hydrogenation reaction is preferably 0°C or higher and 80°C or lower, more preferably 5°C or higher and 70°C or lower, and even more preferably 10°C or higher and 60°C or lower.

[0075] The completion of the hydrogenation reaction can be determined by confirming the presence of the compound represented by formula (I) in the reaction system. The presence or absence of the compound represented by formula (I) can be confirmed, for example, by thin layer chromatography. Alternatively, the amount of the compound represented by formula (I) can be confirmed every 1 to 2 hours using gas chromatography, liquid chromatography, or the like, and the reaction can be considered complete when there is no change or the change in the amount of decrease of the compound represented by formula (I) becomes small. After completion of the hydrogenation reaction, the catalyst can be removed from the reaction system by, for example, filtration. The resulting crude product of the compound represented by formula (V) may be used in the next step as is, or may be purified by means of distillation or the like before use in the next step.

[0076] The method for producing the compound represented by formula (VI) preferably includes the steps of: subjecting the compound represented by formula (I) to a hydrogenation reaction to obtain a compound represented by formula (V); and subjecting the obtained compound represented by formula (V) to a reduction reaction together with an ammonia equivalent in the presence of a transition metal catalyst or in the presence of an ate complex-type hydride reducing agent.

[0077] The method for producing the compound represented by formula (VI) preferably includes the steps of subjecting the compound represented by formula (I) to a hydrogenation reaction to obtain a compound represented by formula (V), and subjecting the obtained compound represented by formula (V) to a reduction reaction together with an ammonia equivalent in the presence of borane.

[0078] The method for producing the compound represented by formula (VI) preferably comprises a step of subjecting the compound represented by formula (V) to a reduction reaction together with an ammonia equivalent, which is at least one selected from the group consisting of ammonium formate, ammonium acetate, ammonium trifluoroacetate, substituted or unsubstituted arylmethylamine, and hexamethyldisilazane, in the presence of a transition metal catalyst or an ate complex-type hydride reducing agent, provided that, at this time, R 1 is an alkyl group having 1 to 8 carbon atoms, preferably a methyl group or an ethyl group, and R 2 is an n-tetradecyl group, and in formula (VI), R 6 is a hydrogen atom or a substituted or unsubstituted arylmethyl group.

[0079] The method for producing the compound represented by formula (VI) preferably comprises a step of subjecting the compound represented by formula (V) to a reduction reaction in the presence of borane together with an ammonia equivalent which is at least one selected from the group consisting of ammonium formate, ammonium acetate, ammonium trifluoroacetate, substituted or unsubstituted arylmethylamine, and hexamethyldisilazane, provided that, at this time, R 1 is an alkyl group having 1 to 8 carbon atoms, preferably a methyl group or an ethyl group, and R 2is an n-tetradecyl group, and in formula (VI), R 6 is a hydrogen atom or a substituted or unsubstituted arylmethyl group.

[0080] <Debenzylation reaction> In the present invention, the debenzylation reaction is a reaction of converting a compound represented by formula (VI) into R 6 The reaction is a hydrogenolysis reaction of a substituted or unsubstituted arylmethyl group represented by formula (VI). 6 is a substituted or unsubstituted arylmethyl group, the substituted or unsubstituted arylmethyl group may be removed by hydrogenolysis in a step of subjecting the compound represented by formula (VI) to a debenzylation reaction after the compound represented by formula (VII) is obtained. The debenzylation reaction may be performed after the optical resolution step described below or after the compound represented by formula (VII) is obtained, but from the viewpoint of improving production efficiency, it is preferably performed before the optical resolution step and the compound represented by formula (VII).

[0081] (catalyst) The debenzylation reaction can be carried out in the presence of any catalyst active in the hydrogenolysis of substituted or unsubstituted arylmethyl groups. The catalysts that can be used are the same as those described above for the hydrogenation reaction of the compound represented by formula (I), and the preferred catalysts are also the same. For example, the compound to be subjected to the debenzylation reaction is R 6In the case of a compound represented by formula (VI) in which R is a substituted or unsubstituted arylmethyl group, the amount of catalyst used is, from the viewpoint of improving production efficiency, such that the molar ratio of the active metal species in the catalyst to the compound represented by formula (VI) (active metal species in the catalyst / compound represented by formula (VI)) is preferably 0.001 or more, more preferably 0.005 or more, and even more preferably 0.01 or more. From the same viewpoint, the molar ratio is preferably 0.2 or less, more preferably 0.1 or less, and even more preferably 0.05 or less. The molar ratio (active metal species in the catalyst / compound represented by formula (VI)) is preferably 0.001 or more and 0.2 or less, more preferably 0.005 or more and 0.1 or less, and even more preferably 0.01 or more and 0.05 or less.

[0082] The hydrogen pressure, reaction solvent, and reaction temperature in the debenzylation reaction are the same as those shown in the hydrogenation reaction of the compound represented by formula (I) above.

[0083] The completion of the debenzylation reaction can be determined by confirming the amount of the compound subjected to the debenzylation reaction. The compound subjected to the debenzylation reaction can be confirmed, for example, by thin layer chromatography. Alternatively, the amount of the compound subjected to the debenzylation reaction can be confirmed every 1 to 2 hours using gas chromatography, liquid chromatography, or the like, and the reaction can be considered complete when there is no change or the change in the amount of the compound subjected to the debenzylation reaction becomes small. After the debenzylation reaction is completed, the catalyst can be removed from the reaction system by, for example, filtration. The resulting crude product may be used in the next step as is, or may be purified by distillation or the like before use in the next step.

[0084] <Optical resolution process> When the compound represented by formula (VI) is a racemate or a mixture of enantiomers, the method for producing the compound represented by formula (VI) may include a step of optically resolving the compound represented by formula (VI). The optical resolution step is a step in which, when the compound represented by formula (VI) is a racemate or an enantiomeric mixture, the compound is subjected to optical resolution to increase the enantiomeric excess of the desired enantiomer. In other words, a method including an optical resolution step can be said to be a method for producing a compound represented by formula (VI) with an increased enantiomeric excess. Examples of optical resolution methods include preferential crystallization, diastereomeric salt method, and chiral column chromatography method. Among these, the diastereomeric salt method using a chiral organic acid is preferred as the optical resolution method from the viewpoint of improving production efficiency. The process for optically resolving the compound represented by formula (VI) by the diastereomeric salt method using a chiral organic acid will be described below.

[0085] (Chiral organic acid) The chiral organic acid can be any chiral organic acid capable of selectively precipitating a crystal of a salt with one enantiomer of the compound represented by formula (VI). From the viewpoint of selectively precipitating a crystal of a salt with one enantiomer of the compound represented by formula (VI), the chiral organic acid is preferably at least one selected from carboxylic acids, amino acids, and sulfonic acids, more preferably at least one selected from (d)-mandelic acid, (1)-mandelic acid, L-tartaric acid, D-tartaric acid, L-glutamic acid, D-glutamic acid, (d)-camphorsulfonic acid, and (1)-camphorsulfonic acid, and even more preferably at least one selected from L-tartaric acid and D-tartaric acid.

[0086] With regard to the amount of chiral organic acid used, from the viewpoint of improving the enantiomeric excess of the compound represented by formula (VI) obtained as a result of the optical resolution step, the molar ratio of the chiral organic acid to the enantiomeric mixture of the compound represented by formula (VI) (chiral organic acid / compound represented by formula (VI)) is preferably 0.8 or more, more preferably 0.9 or more, and even more preferably 1.0 or more. From the same viewpoint, the molar ratio is preferably 10 or less, more preferably 5.0 or less, and even more preferably 2.0 or less. The molar ratio (chiral organic acid / compound represented by formula (VI)) is preferably 0.8 or more and 10 or less, more preferably 0.9 or more and 5.0 or less, and even more preferably 1.0 or more and 2.0 or less.

[0087] The optical resolution of the compound represented by formula (VI) by the diastereomeric salt method using a chiral organic acid can be carried out by a conventional method. For example, the optical resolution of the compound represented by formula (VI) can be carried out by mixing the compound represented by formula (VI), the chiral organic acid, and a solvent, dissolving the compound represented by formula (VI) and the chiral organic acid in the solvent, and then precipitating a crystal of a salt of one enantiomer of the compound represented by formula (VI) with the chiral organic acid. The compound represented by formula (VI) and the chiral organic acid may be heated when dissolved in the solvent, or the solution may be cooled when precipitating the salt crystals. Although there is no particular limitation on the solvent used, from the viewpoint of providing a difference in solubility between the salt of each enantiomer of the compound represented by formula (VI) and a chiral organic acid, the solvent used is preferably at least one selected from highly polar organic solvents and mixed solvents of highly polar organic solvents and water. As the highly polar organic solvent, at least one selected from methanol, ethanol, and 2-propanol is preferred.

[0088] The precipitated crystals of the salt of the compound represented by formula (VI) and the chiral organic acid may be recovered by filtration. The filtered crystals may be mixed with any water-insoluble organic solvent, and a basic aqueous solution may be added to the mixture to dissociate the compound represented by formula (VI) from the chiral organic acid. In this case, the basic aqueous solution is preferably added so that the pH of the aqueous phase after mixing with the mixture is 10 or higher, from the viewpoint of dissociating the compound represented by formula (VI) from the chiral organic acid and extracting the compound represented by formula (VI) into the organic solvent. The compound represented by formula (VI) can be obtained by extracting the compound represented by formula (VI) from the dissociated mixture into an organic solvent by a separation operation or the like. The resulting crude product of the compound represented by formula (VI) may be used directly in the next step, or may be purified by means of distillation or the like before use in the next step.

[0089] The method for producing the compound represented by formula (VI) preferably includes the steps of: subjecting the compound represented by formula (I) to a hydrogenation reaction to obtain a compound represented by formula (V); subjecting the obtained compound represented by formula (V) to a reduction reaction together with an ammonia equivalent in the presence of a transition metal catalyst or in the presence of an ate complex-type hydride reducing agent to obtain a compound represented by formula (VI); and optically resolving the obtained compound represented by formula (VI) with a chiral organic acid.

[0090] The method for producing the compound represented by formula (VI) preferably includes the steps of subjecting the compound represented by formula (I) to a hydrogenation reaction to obtain a compound represented by formula (V), subjecting the obtained compound represented by formula (V) to a reduction reaction together with an ammonia equivalent in the presence of borane to obtain a compound represented by formula (VI), and optically resolving the obtained compound represented by formula (VI) with a chiral organic acid.

[0091] The method for producing the compound represented by formula (VI) preferably comprises the steps of: subjecting the compound represented by formula (V) to a reduction reaction together with an ammonia equivalent, which is at least one selected from the group consisting of ammonium formate, ammonium acetate, ammonium trifluoroacetate, substituted or unsubstituted arylmethylamine, and hexamethyldisilazane, in the presence of a transition metal catalyst or an ate complex-type hydride reducing agent, to obtain the compound represented by formula (VI); and optically resolving the obtained compound represented by formula (VI) with a chiral organic acid, provided that in this case, R 1 is an alkyl group having 1 to 8 carbon atoms, preferably a methyl group or an ethyl group, and R 2 is an n-tetradecyl group, and in formula (VI), R 6 is a hydrogen atom or a substituted or unsubstituted arylmethyl group.

[0092] The method for producing the compound represented by formula (VI) preferably comprises the steps of: subjecting the compound represented by formula (V) to a reduction reaction in the presence of borane together with an ammonia equivalent, which is at least one selected from the group consisting of ammonium formate, ammonium acetate, ammonium trifluoroacetate, substituted or unsubstituted arylmethylamine, and hexamethyldisilazane, to obtain the compound represented by formula (VI); and optically resolving the obtained compound represented by formula (VI) with a chiral organic acid, provided that at this time, R 1 is an alkyl group having 1 to 8 carbon atoms, preferably a methyl group or an ethyl group, and R 2 is an n-tetradecyl group, and in formula (VI), R 6 is a hydrogen atom or a substituted or unsubstituted arylmethyl group.

[0093] [Method for producing the compound represented by formula (VII)] A compound represented by the following formula (VII), 4-alkyl-5-N-acylamino-1,3-dioxane, can be produced by a process comprising a step of subjecting the compound represented by formula (VI) obtained by the above production process and a compound represented by the following formula (VIII) to an amidation (N-acylation) reaction.

[0094] [ka]

[0095] In formula (VII), R 1 represents a hydrogen atom or a hydrocarbon group, and R 2 represents a hydrogen atom or a linear alkyl group, and R 6 represents a hydrogen atom or a substituted or unsubstituted arylmethyl group, R 7 represents a linear alkyl group having 1 to 29 carbon atoms, and X represents a hydroxyl group, an alkoxy group, an alkylcarbonyloxy group, or a halogen atom. 1 a hydrocarbon group represented by R 2 and their preferred ranges are R 1 and R 2 are synonymous with each other. In addition, in formula (VII), R 6 The substituted or unsubstituted arylmethyl group represented by the formula (VI) and the preferred range thereof are 6 is synonymous with. Furthermore, in formula (VII), R 7 From the viewpoint of the usefulness of the compound represented by formula (II) as a synthetic intermediate for producing a sphingoid base, a ceramide, or the like, the linear alkyl group having 1 to 29 carbon atoms as the alkyl group is preferably a linear alkyl group having 5 to 23 carbon atoms, more preferably a linear alkyl group having 7 to 19 carbon atoms, and even more preferably a heptadecyl group.

[0096] (Compound represented by formula (VIII)) In formula (VIII), R 7The linear alkyl group having 1 to 29 carbon atoms represented by the formula (VII) and the preferred range thereof are 7 is synonymous with. Furthermore, the compound represented by formula (VIII) is a carboxylic acid when X is a hydroxyl group, an ester when X is an alkoxy group, an acid anhydride when X is an alkylcarbonyloxy group, or an acid halide when X is a halogen atom. Furthermore, in the formula (VIII), when X is an alkoxy group, the alkoxy group is preferably a methoxy group from the viewpoint of improving production efficiency. In the formula (VIII), when X is an alkylcarbonyloxy group, the alkyl group of the alkylcarbonyloxy group is preferably R 7 It is preferable that the alkyl group is the same as the linear alkyl group. In formula (VIII), when X is a halogen atom, the halogen atom is preferably an atom selected from a chlorine atom and a bromine atom, more preferably a chlorine atom, from the viewpoint of improving production efficiency and the stability of the compound represented by formula (VIII).

[0097] <Amidation reaction> In the present invention, the amidation reaction is a reaction to obtain a compound represented by formula (VII) from a compound represented by formula (VI) and a compound represented by formula (VIII). 6 may be a hydrogen atom or a substituted or unsubstituted arylmethyl group, but is preferably a hydrogen atom from the viewpoint of improving production efficiency. That is, it is preferable that the compound represented by formula (VI) is subjected to the above-mentioned debenzylation reaction before this amidation reaction. In the amidation reaction, the amount of the compound represented by formula (VIII) used is such that the molar ratio of the compound represented by formula (VIII) to the compound represented by formula (VI) (compound represented by formula (VIII) / compound represented by formula (VI)) is preferably 1.0 or more, from the viewpoint of improving production efficiency. From the same viewpoint, the molar ratio is preferably 3.0 or less, more preferably 2.0 or less, and even more preferably 1.5 or less. The molar ratio (compound represented by formula (VIII) / compound represented by formula (VI)) is preferably 1.0 or more and 3.0 or less, more preferably 1.0 or more and 2.0 or less, and even more preferably 1.0 or more and 1.5 or less.

[0098] When the compound represented by formula (VIII) is a carboxylic acid, the amidation reaction can be carried out in the presence of a condensing agent and a condensation auxiliary. Examples of the condensing agent include dicyclohexylcarbodiimide, diisopropylcarbodiimide, 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride, etc. From the viewpoint of improving production efficiency, the amount of the condensing agent used is preferably such that the molar ratio to the carboxylic acid (condensing agent / carboxylic acid) is 1 or more. Examples of the condensation auxiliary include dimethylaminopyridine, N-methylimidazole, 1-hydroxybenzotriazole, 1-hydroxy-7-azabenzotriazole, etc. From the viewpoint of improving production efficiency, the amount of the condensation auxiliary used is preferably such that the molar ratio to the carboxylic acid (condensation auxiliary / carboxylic acid) is 1 or more.

[0099] When the compound of formula (VIII) is a carboxylic acid ester, the amidation reaction can be carried out in the presence of a strong base catalyst. Examples of the strong base catalyst include hydroxides or alkoxides of alkali metals such as sodium hydroxide, sodium methoxide, sodium ethoxide, etc. From the viewpoint of improving production efficiency, the amount of the strong base catalyst used is preferably such that the molar ratio to the carboxylic acid ester (strong base catalyst / carboxylic acid ester) is 0.01 or more.

[0100] When the compound represented by formula (VIII) is an acid anhydride, the amidation reaction can be carried out in the presence of a basic compound. Examples of the basic compound include tertiary amines such as triethylamine, diethylisopropylamine, etc. From the viewpoint of improving production efficiency, the amount of the basic compound used is preferably such that the molar ratio to the acid anhydride (basic compound / acid anhydride) is 1 or more. When the compound represented by formula (VIII) is an acid anhydride, the amidation reaction may be carried out in the presence of a catalyst. As the catalyst, the compounds listed as condensation aids when the compound represented by formula (VIII) is a carboxylic acid can be used, and the amount of catalyst used is preferably such that the molar ratio to the acid anhydride (catalyst / acid anhydride) is 0.01 or more, from the viewpoint of improving production efficiency.

[0101] When the compound represented by formula (VIII) is an acid halide, the amidation reaction can be carried out in the presence of a basic compound. As the basic compound, the basic compounds exemplified when the compound represented by formula (VIII) is an acid anhydride can be used, and the amount of the basic compound used is preferably such that the molar ratio to the acid halide (basic compound / acid halide) is 1 or more, from the viewpoint of improving production efficiency.

[0102] The amidation reaction can be carried out in the presence of any solvent that allows the amidation reaction to proceed.

[0103] From the viewpoint of improving production efficiency, the reaction temperature of the amidation reaction is preferably 0°C or higher, more preferably 5°C or higher, and even more preferably 10°C or higher. From the same viewpoint, the reaction temperature of the amidation reaction is preferably 110°C or lower, more preferably 105°C or lower, and even more preferably 100°C or lower. The reaction temperature of the amidation reaction is preferably 0°C or higher and 110°C or lower, more preferably 5°C or higher and 105°C or lower, and even more preferably 10°C or higher and 100°C or lower.

[0104] The completion of the amidation reaction can be determined by confirming the presence of the compound represented by formula (VI). The presence or absence of the compound represented by formula (VI) can be confirmed, for example, by thin layer chromatography. Treatment after completion of the amidation reaction can be carried out according to a conventional method. Alternatively, the amount of the compound represented by formula (VI) can be confirmed every 1 to 2 hours using gas chromatography, liquid chromatography, or the like, and the reaction can be considered complete when there is no change in the amount of the compound represented by formula (VI) decreasing, or the change in the amount of decrease becomes small. Treatment after the completion of amidation can be carried out according to a conventional method.

[0105] The method for producing a compound represented by formula (VII) preferably comprises, in this order, a step of subjecting a compound represented by formula (I) to a hydrogenation reaction to obtain a compound represented by formula (V); a step of subjecting the obtained compound represented by formula (V) to a reduction reaction together with an ammonia equivalent in the presence of a transition metal catalyst or in the presence of an ate complex-type hydride reducing agent to obtain a compound represented by formula (VI); a step of optically resolving the obtained compound represented by formula (VI) with a chiral organic acid; and a step of subjecting the optically resolved compound represented by formula (VI) and compound represented by formula (VIII) to an amidation reaction. Here, the compound represented by formula (I) may be produced by the method described above in "[Method for producing the compound represented by formula (I)]".

[0106] The method for producing the compound represented by formula (VII) preferably comprises, in this order, a step of subjecting the compound represented by formula (I) to a hydrogenation reaction to obtain a compound represented by formula (V); a step of subjecting the obtained compound represented by formula (V) to a reduction reaction together with an ammonia equivalent in the presence of borane to obtain a compound represented by formula (VI); a step of optically resolving the obtained compound represented by formula (VI) with a chiral organic acid; and a step of subjecting the optically resolved compound represented by formula (VI) and the compound represented by formula (VIII) to an amidation reaction. Here, the compound represented by formula (I) may be produced by the method described above in "[Method for producing the compound represented by formula (I)]".

[0107] The method for producing a compound represented by formula (VII) preferably comprises the steps of: subjecting a compound represented by formula (V) to a reduction reaction together with an ammonia equivalent, which is at least one selected from the group consisting of ammonium formate, ammonium acetate, ammonium trifluoroacetate, substituted or unsubstituted arylmethylamine, and hexamethyldisilazane, in the presence of a transition metal catalyst or in the presence of an ate complex-type hydride reducing agent, to obtain a compound represented by formula (VI); optically resolving the obtained compound represented by formula (VI) with a chiral organic acid; and subjecting the optically resolved compound represented by formula (VI) and the compound represented by formula (VIII) to an amidation reaction, in this order. Here, the compound represented by formula (V) may be a compound represented by formula (V) obtained by subjecting the method for producing the compound represented by formula (I) produced by the method described above in "[Method for producing the compound represented by formula (I)]" to the <hydrogenation reaction> described above in "[Production of the compound represented by formula (V)]".

[0108] The method for producing the compound represented by formula (VII) preferably comprises the steps of: subjecting the compound represented by formula (V) to a reduction reaction in the presence of borane together with an ammonia equivalent which is at least one selected from the group consisting of ammonium formate, ammonium acetate, ammonium trifluoroacetate, substituted or unsubstituted arylmethylamine, and hexamethyldisilazane to obtain the compound represented by formula (VI); optically resolving the obtained compound represented by formula (VI) with a chiral organic acid; and subjecting the optically resolved compound represented by formula (VI) and the compound represented by formula (VIII) to an amidation reaction, in this order. Here, the compound represented by formula (V) may be a compound represented by formula (V) obtained by subjecting the method for producing the compound represented by formula (I) produced by the method described above in "[Method for producing the compound represented by formula (I)]" to the <hydrogenation reaction> described above in "[Production of the compound represented by formula (V)]".

[0109] The method for producing a compound represented by formula (VII) preferably comprises the steps of: subjecting a compound represented by formula (I) to a hydrogenation reaction to obtain a compound represented by formula (V); subjecting the obtained compound represented by formula (V) to a reduction reaction together with a substituted or unsubstituted arylmethylamine in the presence of a transition metal catalyst or in the presence of an ate complex-type hydride reducing agent to obtain a compound represented by formula (VI); subjecting the obtained compound represented by formula (VI) to a debenzylation reaction to obtain a compound represented by formula (VIb): optically resolving the obtained compound represented by formula (VIb) with a chiral organic acid; and subjecting the optically resolved compound represented by formula (VIb) and the compound represented by formula (VIII) to an amidation reaction, in this order. However, in this case, when R 6 is a substituted or unsubstituted arylmethyl group. Here, the compound represented by formula (I) may be produced by the method described above in "[Method for producing the compound represented by formula (I)]".

[0110] [ka]

[0111] The method for producing a compound represented by formula (VII) preferably comprises the steps of: subjecting a compound represented by formula (I) to a hydrogenation reaction to obtain a compound represented by formula (V); subjecting the obtained compound represented by formula (V) to a reduction reaction together with a substituted or unsubstituted arylmethylamine in the presence of a transition metal catalyst or in the presence of an ate complex-type hydride reducing agent to obtain a compound represented by formula (VI); subjecting the obtained compound represented by formula (VI) to a debenzylation reaction to obtain a compound represented by formula (VIb); optically resolving the obtained compound represented by formula (VIb) with a chiral organic acid; and subjecting the optically resolved compound represented by formula (VIb) and the compound represented by formula (VIII) to an amidation reaction, in this order. However, in this case, when R6 is a substituted or unsubstituted arylmethyl group. Here, the compound represented by formula (I) may be produced by the method described above in "[Method for producing the compound represented by formula (I)]".

[0112] The method for producing a compound represented by formula (VII) preferably comprises the steps of: subjecting a compound represented by formula (V) to a reduction reaction together with a substituted or unsubstituted arylmethylamine in the presence of a transition metal catalyst or in the presence of an ate complex-type hydride reducing agent to obtain a compound represented by formula (VI); subjecting the obtained compound represented by formula (VI) to a debenzylation reaction to obtain a compound represented by formula (VIb); optically resolving the obtained compound represented by formula (VIb) with a chiral organic acid; and subjecting the optically resolved compound represented by formula (VIb) and the compound represented by formula (VIII) to an amidation reaction, in this order. However, in this case, R 1 is an alkyl group having 1 to 8 carbon atoms, preferably a methyl group or an ethyl group, and R 2 is an n-tetradecyl group. 6 is a hydrogen atom or a substituted or unsubstituted arylmethyl group. 7 represents a linear alkyl group having from 1 to 29 carbon atoms. In formula (VIII), X represents a hydroxyl group, an alkoxy group, an alkylcarbonyloxy group, or a halogen atom.

[0113] The method for producing the compound represented by formula (VII) preferably comprises the steps of: subjecting a compound represented by formula (V) to a reduction reaction together with a substituted or unsubstituted arylmethylamine in the presence of borane to obtain a compound represented by formula (VI); subjecting the obtained compound represented by formula (VI) to a debenzylation reaction to obtain a compound represented by formula (VIb); subjecting the obtained compound represented by formula (VIb) to an optical resolution using a chiral organic acid; and subjecting the optically resolved compound represented by formula (VIb) and the compound represented by formula (VIII) to an amidation reaction, in this order. However, at this time, R 1 is an alkyl group having 1 to 8 carbon atoms, preferably a methyl group or an ethyl group, and R 2 is an n-tetradecyl group. 6 is a hydrogen atom or a substituted or unsubstituted arylmethyl group. 7 represents a linear alkyl group having from 1 to 29 carbon atoms. In formula (VIII), X represents a hydroxyl group, an alkoxy group, an alkylcarbonyloxy group, or a halogen atom.

[0114] [Method for producing the compound represented by formula (IX)] The compound represented by formula (IX) can be produced by a method comprising subjecting at least one compound selected from the compound represented by formula (VI) and the compound represented by formula (VII) to a deacetalization reaction.

[0115] [ka]

[0116] In formula (VI) and formula (VII), R 1 represents a hydrogen atom or a hydrocarbon group, and R 6 represents a hydrogen atom or a substituted or unsubstituted arylmethyl group. 2 represents a hydrogen atom or a linear alkyl group. 7represents a linear alkyl group having 1 to 29 carbon atoms. 8 represents a hydrogen atom, a substituted or unsubstituted arylmethyl group, or a linear acyl group having 1 to 30 carbon atoms.

[0117] In the present invention, the deacetalization reaction is a reaction in which the 1,3-dioxane structure in the compound represented by formula (VI) and the compound represented by formula (VII) is converted to a 1,3-diol structure by solvolysis such as hydrolysis or alcoholysis in the presence of an acid.

[0118] Examples of the acid used in the deacetalization reaction include inorganic acids such as hydrochloric acid, sulfuric acid, and phosphoric acid, and organic acids such as methanesulfonic acid and paratoluenesulfonic acid. Among these, phosphoric acid is preferred from the viewpoint of improving production efficiency.

[0119] The amount of the acid used may vary depending on the compound to be subjected to the deacetalization reaction. When the compound represented by formula (VI) is subjected to the deacetalization reaction, the amount of acid used is, from the viewpoint of improving production efficiency, such that the molar ratio of protons in the acid to the compound represented by formula (VI) (protons in the acid / compound represented by formula (VI)) is preferably 1.01 or more, more preferably 1.05 or more, even more preferably 1.1 or more, and is preferably 50 or less, more preferably 20 or less, even more preferably 15 or less. When the compound represented by formula (VII) is subjected to the deacetalization reaction, the amount of acid used is, from the viewpoint of improving production efficiency, such that the molar ratio of protons in the acid to the compound represented by formula (VII) (protons in the acid / compound represented by formula (VII)) is preferably 0.01 or more, more preferably 0.05 or more, even more preferably 0.1 or more, and is preferably 50 or less, more preferably 20 or less, even more preferably 15 or less.

[0120] Examples of the solvent used in the deacetalization reaction include water and alcohol, and from the viewpoint of improving production efficiency, a mixed solvent of water and alcohol is preferred. Examples of the alcohol include alcohols having 4 or more carbon atoms, such as 1-butanol, 2-butanol, cyclopentanol, and cyclohexanol, and diols, such as 1,2-propanediol and 1,3-propanediol. When the compound represented by formula (VII) is subjected to the deacetalization reaction, from the viewpoint of suppressing hydrolysis of the amide moiety, the alcohol is preferably a secondary alcohol, and more preferably 2-butanol.

[0121] The reaction temperature of the deacetalization reaction is preferably 90° C. or higher, more preferably 100° C. or higher, and even more preferably 110° C. or higher from the viewpoint of improving production efficiency, and is preferably 150° C. or lower, more preferably 140° C. or lower, and even more preferably 130° C. or lower from the viewpoint of suppressing side reactions. The reaction temperature of the deacetalization reaction is preferably 90° C. or higher and 150° C. or lower, more preferably 100° C. or higher and 140° C. or lower, and even more preferably 110° C. or higher and 130° C. The deacetalization reaction may be carried out under normal pressure or under reduced pressure.

[0122] The completion of the deacetalization reaction can be determined by confirming the presence of the compound represented by formula (VI) and / or the compound represented by formula (VII) in the reaction system. The presence or absence of the compound represented by formula (VI) and / or the compound represented by formula (VII) can be confirmed, for example, by thin-layer chromatography. Alternatively, the amount of the compound represented by formula (VI) and / or the compound represented by formula (VII) can be confirmed every 1 to 2 hours using gas chromatography, liquid chromatography, or the like, and the reaction can be considered complete when there is no change or the change in the amount of decrease of the compound represented by formula (VI) and / or the compound represented by formula (VII) becomes small.

[0123] After the completion of the deacetalization reaction, neutralization is carried out with a basic compound, and further purification is carried out by a conventional method to obtain the compound represented by formula (IX).

[0124] The method for producing the compound represented by formula (IX) is preferably a method for producing any one selected from the compound represented by formula (IX-1) and the compound represented by formula (IX-2) below by deacetalizing any one selected from the compound represented by formula (VI-1) below and the compound represented by formula (VII-1) below.

[0125] [ka]

[0126] In formula (VI-1) and formula (VII-1), R 1 represents R in the above formula (VI) and formula (VII). 1 The same applies to the preferred range.

[0127] The present invention includes the following aspects. <a1>A compound represented by the following formula (I): [ka] (In formula (I), R 1 represents a hydrogen atom or a hydrocarbon group, and R 2 represents a hydrogen atom or a linear alkyl group. <a2>In the formula (I), R 1 is a group selected from an alkyl group, an alkenyl group, and an alkynyl group, preferably an alkyl group having 1 to 8 carbon atoms, more preferably a methyl group or an ethyl group; <a1>The compound described in <a3>In the formula (I), R 2 is a hydrogen atom or a linear alkyl group having from 1 to 21 carbon atoms, preferably a linear alkyl group having from 8 to 18 carbon atoms, more preferably an n-tetradecyl group; <a1>or <a2>The compound described in <a4>In the formula (I), R 1 is a group selected from an alkyl group, an alkenyl group, and an alkynyl group, and R 2 is a linear alkyl group having 8 to 18 carbon atoms, <a1> ~ <a3>The compound described in <a5>In the formula (I), R 1 is an alkyl group having 1 to 8 carbon atoms, and R 2 is a linear alkyl group having 8 to 18 carbon atoms, <a1> ~ <a4>The compound described in <a6>In the formula (I), R 1 is a methyl group or an ethyl group, and R 2 is an n-tetradecyl group, <a1> ~ <a3>The compound described in <b1>A method for producing a compound represented by the following formula (I), comprising a step of subjecting a compound represented by the following formula (II) and a compound represented by the following formula (III) to an aldol condensation reaction in the presence of a compound represented by the following formula (IV): [ka] (In formula (I), formula (II), formula (III), and formula (IV), R 1 represents a hydrogen atom or a hydrocarbon group, and R 2 represents a hydrogen atom or a linear alkyl group. 3 , R 4 , and R 5 each independently represents a group selected from a hydrogen atom, a hydroxyl group, an alkoxy group, an N,N-dialkylamino group, an alkoxymethyl group, an N,N-dialkylaminomethyl group, a carboxy group, a carbamoyl group, an acyloxy group, an acylamino group, a silyloxy group, an alkoxycarbonyloxy group, and an alkoxycarbonylamino group. <b2>In the formula (I) and the formula (II), R 1 is a group selected from an alkyl group, an alkenyl group, and an alkynyl group, preferably an alkyl group having 1 to 8 carbon atoms, more preferably a methyl group or an ethyl group; <b1>The manufacturing method described in <b3>The compound represented by formula (II) is a compound obtained by oxidizing a mixture of 5-hydroxy-1,3-dioxane and 4-hydroxymethyltetrahydrofuran under oxidative esterification conditions, The method further comprises a step of producing the compound represented by formula (II) by a method comprising a step of oxidizing a mixture of 5-hydroxy-1,3-dioxane and 4-hydroxymethyltetrahydrofuran under oxidative esterification conditions. <b1>or <b2>The manufacturing method described in <b4>In the formula (III), R 2 is a hydrogen atom or a linear alkyl group having from 1 to 21 carbon atoms, preferably a linear alkyl group having from 8 to 18 carbon atoms, more preferably an n-tetradecyl group; <b1> ~ <b3>1. The manufacturing method according to any one of the preceding claims. <b5>The method further comprises a step of producing the compound represented by formula (III) by oxidation of an alcohol or hydroformylation of an α-olefin. <b1> ~ <b4>1. The manufacturing method according to any one of the preceding claims. <b6>In the formula (IV), R 3 is at least one selected from a hydrogen atom and a carboxy group, preferably a hydrogen atom, and R 4 and R 5 is at least one selected from a hydroxyl group, an alkoxy group, an N,N-dialkylamino group, an alkoxymethyl group, an N,N-dialkylaminomethyl group, a carboxy group, a carbamoyl group, an acyloxy group, an acylamino group, an alkoxycarbonyloxy group, and an alkoxycarbonylamino group, preferably at least one selected from a hydroxyl group, an alkoxy group, an N,N-dialkylamino group, an acylamino group, an alkoxycarbonyloxy group, and an alkoxycarbonylamino group, <b1> ~ <b5>1. The manufacturing method according to any one of the preceding claims. <b7>In the formula (I) and formula (II), R 1 is a hydrocarbon group, and the enantiomeric excess of the compound represented by formula (IV) is 90% ee or more. <b1> ~ <b6>1. The manufacturing method according to any one of the preceding claims. <b8>In the formula (I) and the formula (II), R 1 represents a group selected from an alkyl group, an alkenyl group, and an alkynyl group, preferably an alkyl group having from 1 to 8 carbon atoms, more preferably a methyl group or an ethyl group, In the formula (I) and the formula (III), R 2 is an n-tetradecyl group, In the formula (IV), R 3 is a hydrogen atom, and R 4 and R 5 are each independently at least one selected from a hydroxyl group, an alkoxy group, an N,N-dialkylamino group, an acylamino group, an alkoxycarbonyloxy group and an alkoxycarbonylamino group, <b1> ~ <b7>1. The manufacturing method according to any one of the preceding claims. <b9>The compound represented by formula (IV) is at least one selected from proline, 3-pyrrolidinol, 3,4-pyrrolidinediol, 3-acetamidopyrrolidine, and 3-(tert-butoxycarbonylamino)pyrrolidine, preferably at least one selected from 3-pyrrolidinol and 3,4-pyrrolidinediol. <b1> ~ <b8>1. The manufacturing method according to any one of the preceding claims. <b10>the molar ratio of the compound represented by formula (II) to the compound represented by formula (III) (compound represented by formula (II) / compound represented by formula (III)) is 1.0 or more and 3.5 or less; <b1> ~ <b9>1. The manufacturing method according to any one of the preceding claims. <b11>the molar ratio to the compound represented by formula (III) (compound represented by formula (IV) / compound represented by formula (III)) is 0.1 or more and 1.5 or less, preferably 0.15 or more and 1.2 or less, more preferably 0.2 or more and 1.1 or less; <b1> ~ <b10>1. The manufacturing method according to any one of the preceding claims. <b12>the step of subjecting the compound to aldol condensation is carried out in the presence of a solvent, preferably a solvent selected from alcohol, ether, alkyl halide, nitrile, and hydrocarbon, more preferably a solvent selected from methyl tert-butyl ether, ethyl tert-butyl ether, cyclopentyl methyl ether, chloroform, diethylene glycol monoethyl ether, 2-propanol, dichloromethane, acetonitrile, toluene, octane, and hexane, and even more preferably a solvent selected from methyl tert-butyl ether, ethyl tert-butyl ether, and cyclopentyl methyl ether; <b1> ~ <b11>1. The manufacturing method according to any one of the preceding claims. <b13>the step of subjecting the compound to an aldol condensation reaction is carried out in the presence of a carboxylic acid. <b1> ~ <b12>1. The manufacturing method according to any one of the preceding claims. <b14>The carboxylic acid is an aliphatic monocarboxylic acid, preferably a carboxylic acid selected from formic acid, acetic acid, and propionic acid, more preferably acetic acid; <b13>The manufacturing method described in <b15>the molar ratio of the carboxylic acid to the compound represented by formula (III) (carboxylic acid / compound represented by formula (III)) is greater than 0 and less than 70, preferably greater than 1.0 and less than 60, and more preferably greater than 3.0 and less than 50; <b13>or <b14>The manufacturing method described in <b16>In the step of subjecting the mixture to an aldol condensation reaction, the compound represented by formula (IV) is added to a mixture of the compound represented by formula (II) and the compound represented by formula (III). <b1> ~ <b15>1. The manufacturing method according to any one of the preceding claims. <b17>In the step of subjecting the mixture to an aldol condensation reaction, the reaction temperature is 0°C or higher and 50°C or lower, preferably 10°C or higher and 40°C or lower, and more preferably 15°C or higher and 30°C or lower. <b1> ~ <b16>1. The manufacturing method according to any one of the preceding claims. <b18>In the step of subjecting the reaction system to the aldol condensation reaction, water or an aqueous solution of an inorganic salt is added to the reaction system and the system is stirred to terminate the aldol condensation reaction. <b1> ~ <b17>1. The manufacturing method according to any one of the preceding claims. <c1> <b1> ~ <b18>1. A method for producing a compound represented by formula (V), comprising a step of subjecting a compound represented by formula (I) obtained by any one of the production methods described above to a hydrogenation reaction. [ka] (In formula (V), R 1 represents a hydrogen atom or a hydrocarbon group, and R 2 represents a hydrogen atom or a linear alkyl group. <c2>In the formula (V), R 1 is a hydrocarbon group, preferably a group selected from an alkyl group, an alkenyl group, and an alkynyl group, more preferably an alkyl group having 1 to 8 carbon atoms, and even more preferably a methyl group or an ethyl group; <c1>The manufacturing method described in <c3>In the formula (V), R 2 is a hydrogen atom or a linear alkyl group having 1 to 21 carbon atoms, preferably a linear alkyl group having 8 to 18 carbon atoms, more preferably an n-tetradecyl group; <c1>or <c2>The manufacturing method described in <c4>a step of subjecting the product to a hydrogenation reaction is carried out in the presence of a catalyst, preferably at least one selected from a catalyst in which a platinum group element and / or a hydroxide thereof is supported on a carrier, and a sponge metal catalyst, more preferably at least one selected from a palladium carbon catalyst, a palladium hydroxide carbon catalyst, and a sponge nickel catalyst, more preferably at least one selected from a palladium carbon catalyst and a palladium hydroxide carbon catalyst; <c1> ~ <c3>1. The manufacturing method according to any one of the preceding claims. <c5>the molar ratio of the active metal species in the catalyst to the compound represented by formula (I) (active metal species in the catalyst / compound represented by formula (I)) is 0.001 or more and 0.2 or less, preferably 0.005 or more and 0.1 or less, and more preferably 0.01 or more and 0.05 or less; <c4>The manufacturing method described in <c6>The step of subjecting the mixture to a hydrogenation reaction is carried out under a hydrogen pressure of from atmospheric pressure to 2.0 MPa, preferably from 0.05 MPa to 1.0 MPa in gauge pressure, more preferably from 0.1 MPa to 0.5 MPa in gauge pressure. <c1> ~ <c5>1. The manufacturing method according to any one of the preceding claims. <c7>The step of subjecting the mixture to a hydrogenation reaction is carried out in the presence of a solvent. <c1> ~ <c6>1. The manufacturing method according to any one of the preceding claims. <c8>The solvent is at least one selected from alcohols, ethers, esters, and alkyl halides, preferably at least one selected from methanol, ethanol, 2-propanol, tetrahydrofuran, methyl tert-butyl ether, ethyl tert-butyl ether, cyclopentyl methyl ether, ethyl acetate, dichloromethane, 1,2-dichloroethane, and chloroform, more preferably at least one selected from methanol, ethanol, 2-propanol, tetrahydrofuran, methyl tert-butyl ether, ethyl tert-butyl ether, cyclopentyl methyl ether, and ethyl acetate; <c7>The manufacturing method described in <c9>In the step of subjecting the mixture to a hydrogenation reaction, the reaction temperature is 0°C or higher and 80°C or lower, preferably 5°C or higher and 70°C or lower, and more preferably 10°C or higher and 60°C or lower. <c1> ~ <c8>1. The manufacturing method according to any one of the preceding claims. <d1>A method for producing a compound represented by the following formula (VI), comprising a step of subjecting a compound represented by the following formula (V) to a reduction reaction together with an ammonia equivalent. [ka] (In formula (V) and formula (VI), R 1 represents a hydrogen atom or a hydrocarbon group, and R 2 represents a hydrogen atom or a linear alkyl group. 6 represents a hydrogen atom or a substituted or unsubstituted arylmethyl group. <d2> <c1> ~ <c9>1. A method for producing a compound represented by the following formula (VI), comprising a step of subjecting a compound represented by formula (V) obtained by any one of the production methods described above to a reduction reaction together with an ammonia equivalent. [ka] (In formula (VI), R 1 represents a hydrogen atom or a hydrocarbon group, and R 2 represents a hydrogen atom or a linear alkyl group. 6 represents a hydrogen atom or a substituted or unsubstituted arylmethyl group. <d3>In the formula (V) and the formula (VI), R 1 is an alkyl group having 1 to 8 carbon atoms, preferably a methyl group or an ethyl group; <d1>or <d2>The manufacturing method described in <d4>In the formula (VI), R 2 is a hydrogen atom or a linear alkyl group having 1 to 21 carbon atoms, preferably a linear alkyl group having 8 to 18 carbon atoms, more preferably an n-tetradecyl group; <d1> ~ <d3>1. The manufacturing method according to any one of the preceding claims. <d5>In the formula (VI), R 6 is a substituted or unsubstituted arylmethyl group, preferably a benzyl group; <d1> ~ <d4>1. The manufacturing method according to any one of the preceding claims. <d6>the arylmethyl group has a substituent, and the substituent is substituted with an aryl group; <d5>The manufacturing method described in <d7>The ammonia equivalent is at least one selected from an ammonium salt of a carboxylic acid, a substituted or unsubstituted arylmethylamine, and a disilazane, and preferably at least one selected from ammonium formate, ammonium acetate, ammonium trifluoroacetate, a substituted or unsubstituted arylmethylamine, and hexamethyldisilazane. <d1> ~ <d6>1. The manufacturing method according to any one of the preceding claims. <d8>The ammonia equivalent is an ammonium salt of the carboxylic acid, and the molar ratio of the ammonia equivalent to the compound represented by formula (V) (ammonia equivalent / compound represented by formula (V)) is 1 or more and 20 or less, preferably 3 or more and 15 or less, and more preferably 5 or more and 12 or less. <d7>The manufacturing method described in <d9>the ammonia equivalent is the substituted or unsubstituted arylmethylamine or the disilazane, and the molar ratio of the substituted or unsubstituted arylmethylamine or the disilazane to the compound represented by formula (V) (substituted or unsubstituted arylmethylamine or disilazane / compound represented by formula (V)) is 0.8 or more and 10 or less, preferably 0.9 or more and 5 or less, and more preferably 1 or more and 3 or less; <d7>The manufacturing method described in <d10>The reduction reaction is carried out in the presence of a transition metal catalyst or an ate complex type hydride reducing agent. <d1> ~ <d9>1. The manufacturing method according to any one of the preceding claims. <d11>A step of subjecting a compound represented by the following formula (I) to a hydrogenation reaction to obtain a compound represented by the following formula (V): a step of subjecting the compound represented by formula (V) to a reduction reaction together with an ammonia equivalent in the presence of a transition metal catalyst or in the presence of an ate complex type hydride reducing agent; having <d2> ~ <d10>1. A method for producing a compound represented by the following formula (VI) according to any one of the above. [ka] (In formula (I), formula (V), and formula (VI), R 1 represents a hydrogen atom or a hydrocarbon group, and R 2 represents a hydrogen atom or a linear alkyl group. 6 represents a hydrogen atom or a substituted or unsubstituted arylmethyl group. <d12>A step of subjecting a compound represented by the following formula (I) to a hydrogenation reaction to obtain a compound represented by the following formula (V): a step of subjecting the compound represented by formula (V) to a reduction reaction together with an ammonia equivalent in the presence of a transition metal catalyst or in the presence of an ate complex type hydride reducing agent; A method for producing a compound represented by the following formula (VI): [ka] (In formula (I), formula (V), and formula (VI), R 1 represents a hydrogen atom or a hydrocarbon group, and R 2 represents a hydrogen atom or a linear alkyl group. 6 represents a hydrogen atom or a substituted or unsubstituted arylmethyl group. <d13>In the step of subjecting the compound to a reduction reaction, the reduction reaction is carried out in the presence of hydrogen or ammonium formate, preferably in the presence of hydrogen or ammonium formate and a transition metal catalyst. <d1> ~ <d12>The manufacturing method according to any one of the above, In the production method, when the transition metal catalyst is used, the transition metal catalyst is preferably at least one selected from a catalyst in which a platinum group element and / or a hydroxide thereof is supported on a carrier, and a sponge metal catalyst, more preferably at least one selected from a palladium carbon catalyst, a palladium hydroxide carbon catalyst, and a sponge nickel catalyst, and even more preferably at least one selected from a palladium carbon catalyst and a palladium hydroxide carbon catalyst. <d14>A method for producing a compound represented by formula (VI), wherein in the step of subjecting to a reduction reaction, the reduction reaction is carried out in the presence of hydrogen or ammonium formate, preferably in the presence of hydrogen or ammonium formate and a transition metal catalyst, In the production method, when the transition metal catalyst is used, the transition metal catalyst is preferably at least one selected from a catalyst in which a platinum group element and / or a hydroxide thereof is supported on a carrier, and a sponge metal catalyst, more preferably at least one selected from a palladium carbon catalyst, a palladium hydroxide carbon catalyst, and a sponge nickel catalyst, and even more preferably at least one selected from a palladium carbon catalyst and a palladium hydroxide carbon catalyst. <d15>A method for producing a compound represented by the following formula (VI), comprising a step of subjecting a compound represented by the following formula (V) to a reduction reaction together with an ammonia equivalent in the presence of a transition metal catalyst or in the presence of an ate complex-type hydride reducing agent, The production method, wherein the ammonia equivalent is at least one selected from the group consisting of ammonium formate, ammonium acetate, ammonium trifluoroacetate, substituted or unsubstituted arylmethylamine, and hexamethyldisilazane. [ka] (In formula (V) and formula (VI), R 1 represents an alkyl group having 1 to 8 carbon atoms, preferably a methyl group or an ethyl group, and R 2 represents an n-tetradecyl group. 6 represents a hydrogen atom or a substituted or unsubstituted arylmethyl group. <d16>the molar ratio of the active metal species in the transition metal catalyst to the compound represented by formula (V) (active metal species in the transition metal catalyst / compound represented by formula (V)) is 0.001 or more and 0.2 or less, preferably 0.005 or more and 0.1 or less, and preferably 0.01 or more and 0.05 or less; <d13> ~ <d15>1. The manufacturing method according to any one of the preceding claims. <d17>the step of subjecting the compound to a reduction reaction is carried out in the presence of an ate complex-type hydride reducing agent, preferably sodium triacetoxyborohydride; <d15>The manufacturing method described in <d18>the molar ratio of the hydride ion in the ate complex hydride reducing agent to the compound represented by formula (V) (hydride ion in the ate complex hydride reducing agent / compound represented by formula (V)) is 1.0 or more and 10 or less, preferably 1.2 or more, and more preferably 1.4 or more and 5 or less, and the molar ratio is preferably 10 or less and 3 or less; <d17>The manufacturing method described in <d19>Hydrogen is used as the reducing agent, and the hydrogen pressure of the hydrogen gas is a gauge pressure of 0 MPa or more and 2.0 MPa or less, preferably a gauge pressure of 0.05 MPa or more and 1.0 MPa or less, and more preferably a gauge pressure of 0.1 MPa or more and 0.5 MPa or less. <d13> ~ <d16>1. The manufacturing method according to any one of the preceding claims. <d20>the step of subjecting the compound to a reduction reaction is carried out in the presence of ammonium formate, and the molar ratio of ammonium formate to the compound represented by formula (V) (ammonium formate / compound represented by formula (V)) is 1 or more and 20 or less, preferably 3 or more and 15 or less, and more preferably 5 or more and 12 or less; <d13> ~ <d16>The manufacturing method described in <d21>The step of subjecting the compound to a reduction reaction is carried out in the presence of borane, preferably at least one selected from 2-picoline borane complex and 5-ethyl-2-methylpyridine borane complex, more preferably 2-picoline borane complex. <d1> ~ <d11>1. The manufacturing method according to any one of the preceding claims. <d22>A step of subjecting a compound represented by the following formula (I) to a hydrogenation reaction to obtain a compound represented by the following formula (V): a step of subjecting the compound represented by formula (V) to a reduction reaction together with an ammonia equivalent in the presence of borane; A method for producing a compound represented by the following formula (VI): [ka] (In formula (I), formula (V), and formula (VI), R 1 represents a hydrogen atom or a hydrocarbon group, and R 2 represents a hydrogen atom or a linear alkyl group. 6 represents a hydrogen atom or a substituted or unsubstituted arylmethyl group. <d23>A method for producing a compound represented by the following formula (VI), comprising a step of subjecting a compound represented by the following formula (V) to a reduction reaction together with an ammonia equivalent in the presence of borane, The production method, wherein the ammonia equivalent is at least one selected from the group consisting of ammonium formate, ammonium acetate, ammonium trifluoroacetate, substituted or unsubstituted arylmethylamine, and hexamethyldisilazane. [ka] (In formula (V) and formula (VI), R 1 represents an alkyl group having 1 to 8 carbon atoms, preferably a methyl group or an ethyl group, and R 2 represents an n-tetradecyl group. 6 represents a hydrogen atom or a substituted or unsubstituted arylmethyl group. <d24>the molar ratio of the borane to the compound represented by formula (V) (borane / compound represented by formula (V)) is 0.3 or more and 5 or less, preferably 0.4 or more and 3 or less, and more preferably 0.5 or more and 2.5 or less; <d21> ~ <d23>1. The manufacturing method according to any one of the preceding claims. <d25>the step of subjecting the compound to a reduction reaction is carried out in the presence of an acid, preferably at least one selected from Lewis acids and carboxylic acids having 1 to 6 carbon atoms, more preferably at least one selected from scandium trifluoromethanesulfonate (scandium triflate), formic acid, acetic acid, and propionic acid, and even more preferably at least one selected from scandium trifluoromethanesulfonate and acetic acid; <d1> ~ <d24>1. The manufacturing method according to any one of the preceding claims. <d26>The Lewis acid is used as the acid, and the molar ratio of the Lewis acid to the compound represented by formula (V) (Lewis acid / compound represented by formula (V)) is 0.001 or more and 1 or less, preferably 0.05 or more and 0.5 or less, and more preferably 0.01 or more and 0.2 or less. <d25>The manufacturing method described in <d27>the acid is a carboxylic acid having from 1 to 6 carbon atoms, and the molar ratio of the carboxylic acid having from 1 to 6 carbon atoms to the compound represented by formula (V) (carboxylic acid having from 1 to 6 carbon atoms / compound represented by formula (V)) is from 0.1 to 30, preferably from 0.5 to 20, and more preferably from 0.8 to 10; <d25>The manufacturing method described in <d28>the step of subjecting the product to a reduction reaction is carried out in the presence of a solvent, preferably at least one selected from alcohols, ethers, and alkyl halides, more preferably at least one selected from methanol, ethanol, 2-propanol, tetrahydrofuran, methyl tert-butyl ether, ethyl tert-butyl ether, cyclopentyl methyl ether, dichloromethane, 1,2-dichloroethane, and chloroform, and even more preferably at least one selected from methanol, ethanol, 2-propanol, tetrahydrofuran, methyl tert-butyl ether, ethyl tert-butyl ether, and cyclopentyl methyl ether; <d1> ~ <d27>1. The manufacturing method according to any one of the preceding claims. <d29>In the step of subjecting the mixture to a reduction reaction, the reducing agent is added to a mixture of raw materials other than the reducing agent. <d1> ~ <d28>1. The manufacturing method according to any one of the preceding claims. <d30>In the step of subjecting the mixture to a reduction reaction, the reaction temperature is 0°C or higher and 80°C or lower, preferably 5°C or higher and 70°C or lower, and more preferably 10°C or higher and 60°C or lower. <d1> ~ <d29>1. The manufacturing method according to any one of the preceding claims. <d31> <d1> ~ <d30>R of the compound represented by formula (VI) obtained by any one of the production methods described in 6 is a substituted or unsubstituted arylmethyl group, the compound of formula (VI) being subjected to a debenzylation reaction, 6 A method for producing a compound represented by formula (VI), wherein <d32>The debenzylation reaction is carried out in the presence of a catalyst, preferably at least one selected from a catalyst in which a platinum group element and / or a hydroxide thereof is supported on a carrier and a sponge metal catalyst, more preferably at least one selected from a palladium carbon catalyst, a palladium hydroxide carbon catalyst, and a sponge nickel catalyst, and even more preferably at least one selected from a palladium carbon catalyst and a palladium hydroxide carbon catalyst; <d31>The manufacturing method described in <d33>the molar ratio of the active metal species in the catalyst to the compound represented by formula (VI) (active metal species in the catalyst / compound represented by formula (VI)) is 0.001 or more and 0.2 or less, preferably 0.005 or more and 0.1 or less, more preferably 0.01 or more and 0.05 or less; <d32>The manufacturing method described in <d34>The debenzylation reaction is carried out under a hydrogen pressure of preferably from atmospheric pressure to 2.0 MPa, more preferably from 0.05 MPa to 1.0 MPa, more preferably from 0.1 MPa to 0.5 MPa. <d31> ~ <d33>1. The manufacturing method according to any one of the preceding claims. <d35>The debenzylation reaction is carried out in the presence of a solvent. <d31> ~ <d34>1. The manufacturing method according to any one of the preceding claims. <d36>The solvent is preferably at least one selected from alcohols, ethers, esters, and alkyl halides, more preferably at least one selected from methanol, ethanol, 2-propanol, tetrahydrofuran, methyl tert-butyl ether, ethyl tert-butyl ether, cyclopentyl methyl ether, ethyl acetate, dichloromethane, 1,2-dichloroethane, and chloroform, and even more preferably at least one selected from methanol, ethanol, 2-propanol, tetrahydrofuran, methyl tert-butyl ether, ethyl tert-butyl ether, cyclopentyl methyl ether, and ethyl acetate. <d35>The manufacturing method described in <d37>In the debenzylation reaction, the reaction temperature is 0°C or higher and 80°C or lower, preferably 5°C or higher and 70°C or lower, and more preferably 10°C or higher and 60°C or lower. <d31> ~ <d36>1. The manufacturing method according to any one of the preceding claims. <d38> <d1> ~ <d37>The compound represented by formula (VI) is preferably R 6 is a hydrogen atom, the method for producing a compound of formula (VI) with an increased enantiomeric excess, or the method for increasing the enantiomeric excess of a compound of formula (VI), comprising a step of optically resolving the compound when the compound of formula (VI) in which <d39>The optical resolution step is a diastereomeric salt method using a chiral organic acid. <d38>The manufacturing method or method described in <d40>A step of subjecting a compound represented by the following formula (I) to a hydrogenation reaction to obtain a compound represented by the following formula (V): a step of subjecting the compound represented by formula (V) to a reduction reaction together with an ammonia equivalent in the presence of a transition metal catalyst or in the presence of an ate complex type hydride reducing agent to obtain a compound represented by the following formula (VI); a step of optically resolving the compound represented by formula (VI) using a chiral organic acid; A method for producing a compound represented by the following formula (VI): [ka] (In formula (I), formula (V), and formula (VI), R 1 represents a hydrogen atom or a hydrocarbon group, and R 2 represents a hydrogen atom or a linear alkyl group. 6 represents a hydrogen atom or a substituted or unsubstituted arylmethyl group. <d41>A step of subjecting a compound represented by the following formula (I) to a hydrogenation reaction to obtain a compound represented by the following formula (V): a step of subjecting the compound represented by formula (V) to a reduction reaction together with an ammonia equivalent in the presence of borane to obtain a compound represented by the following formula (VI); a step of optically resolving the compound represented by formula (VI) using a chiral organic acid; A method for producing a compound represented by the following formula (VI): [ka] (In formula (I), formula (V), and formula (VI), R 1 represents a hydrogen atom or a hydrocarbon group, and R 2 represents a hydrogen atom or a linear alkyl group. 6 represents a hydrogen atom or a substituted or unsubstituted arylmethyl group. <d42>A step of subjecting a compound represented by the following formula (V) to a reduction reaction together with an ammonia equivalent in the presence of a transition metal catalyst or in the presence of an ate complex-type hydride reducing agent to obtain a compound represented by the following formula (VI); a step of optically resolving the compound represented by formula (VI) using a chiral organic acid; A method for producing a compound represented by the following formula (VI): The production method, wherein the ammonia equivalent is at least one selected from the group consisting of ammonium formate, ammonium acetate, ammonium trifluoroacetate, substituted or unsubstituted arylmethylamine, and hexamethyldisilazane. [ka] (In formula (V) and formula (VI), R 1 represents an alkyl group having 1 to 8 carbon atoms, preferably a methyl group or an ethyl group, and R 2 represents an n-tetradecyl group. 6 represents a hydrogen atom or a substituted or unsubstituted arylmethyl group. <d43>A step of subjecting a compound represented by the following formula (V) to a reduction reaction together with an ammonia equivalent in the presence of borane to obtain a compound represented by the following formula (VI); a step of optically resolving the compound represented by formula (VI) using a chiral organic acid; A method for producing a compound represented by the following formula (VI): The production method, wherein the ammonia equivalent is at least one selected from the group consisting of ammonium formate, ammonium acetate, ammonium trifluoroacetate, substituted or unsubstituted arylmethylamine, and hexamethyldisilazane. [ka] (In formula (V) and formula (VI), R 1 represents an alkyl group having 1 to 8 carbon atoms, preferably a methyl group or an ethyl group, and R 2 represents an n-tetradecyl group. 6 represents a hydrogen atom or a substituted or unsubstituted arylmethyl group. <d44>The chiral organic acid is at least one selected from carboxylic acids, amino acids, and sulfonic acids, preferably at least one selected from (d)-mandelic acid, (1)-mandelic acid, L-tartaric acid, D-tartaric acid, L-glutamic acid, D-glutamic acid, (d)-camphorsulfonic acid, and (1)-camphorsulfonic acid, more preferably at least one selected from L-tartaric acid and D-tartaric acid. <d39> ~ <d43>1. The manufacturing method or method according to any one of the preceding claims. <d45>the molar ratio of the chiral organic acid to the enantiomer mixture of the compound represented by formula (VI) (chiral organic acid / compound represented by formula (VI)) is 0.8 or more and 10 or less, preferably 0.9 or more and 5 or less, more preferably 1.0 or more and 2 or less; <d39> ~ <d44>1. The manufacturing method or method according to any one of the preceding claims. <d46>a racemate or a mixture of enantiomers of the compound represented by formula (VI), the chiral organic acid, and a solvent are mixed, the compound represented by formula (VI) and the chiral organic acid are dissolved in the solvent, and then crystals of a salt of at least one enantiomer of the compound represented by formula (VI) and the chiral organic acid are precipitated; <d39> ~ <d45>1. The manufacturing method or method according to any one of the preceding claims. <d47>the solvent is at least one selected from a highly polar organic solvent and a mixed solvent of a highly polar organic solvent and water, The highly polar organic solvent is at least one selected from methanol, ethanol, and 2-propanol. <d46>The manufacturing method or method described in <e1> <d1> ~ <d47>A method for producing a compound represented by the following formula (VII), comprising a step of subjecting a compound represented by formula (VI) obtained by any of the production methods described above, and a compound represented by the following formula (VIII), to an amidation (N-acylation) reaction. [ka] (In formula (VII), R 1 represents a hydrogen atom or a hydrocarbon group, and R 2 represents a hydrogen atom or a linear alkyl group, and R 6 represents a hydrogen atom or a substituted or unsubstituted arylmethyl group, R 7 represents a linear alkyl group having 1 to 29 carbon atoms. In formula (VIII), X represents a hydroxyl group, an alkoxy group, an alkylcarbonyloxy group, or a halogen atom. <e2>In the formula (VI), R 6 is a substituted or unsubstituted arylmethyl group, the method further comprises a step of subjecting the compound represented by formula (VI) to a debenzylation reaction. <e1>The method described below. <e3>A step of subjecting a compound represented by the following formula (I) to a hydrogenation reaction to obtain a compound represented by the following formula (V): a step of subjecting the compound represented by formula (V) to a reduction reaction together with a substituted or unsubstituted arylmethylamine in the presence of a transition metal catalyst or in the presence of an ate complex hydride reducing agent to obtain a compound represented by formula (VI): a step of subjecting the compound represented by formula (VI) to a debenzylation reaction to obtain a compound represented by the following formula (VIb); a step of optically resolving the compound represented by formula (VIb) using a chiral organic acid; a step of subjecting the optically resolved compound represented by formula (VIb) and a compound represented by formula (VIII) below to an amidation reaction; A method for producing a compound represented by the following formula (VIIb), which has the following in this order: [ka] (In formula (I), formula (V), formula (VI), formula (VIb), and formula (VIIb), R 1 represents a hydrogen atom or a hydrocarbon group, and R 2 represents a hydrogen atom or a linear alkyl group. 6 represents a substituted or unsubstituted arylmethyl group. 7 represents a linear alkyl group having 1 to 29 carbon atoms. In formula (VIII), X represents a hydroxyl group, an alkoxy group, an alkylcarbonyloxy group, or a halogen atom. <e4>A step of subjecting a compound represented by the following formula (I) to a hydrogenation reaction to obtain a compound represented by the following formula (V): a step of subjecting the compound represented by formula (V) to a reduction reaction together with a substituted or unsubstituted arylmethylamine in the presence of borane to obtain a compound represented by the following formula (VI); a step of subjecting the compound represented by formula (VI) to a debenzylation reaction to obtain a compound represented by the following formula (VIb); a step of optically resolving the compound represented by formula (VIb) using a chiral organic acid; a step of subjecting the optically resolved compound represented by formula (VIb) and a compound represented by formula (VIII) below to an amidation reaction; A method for producing a compound represented by the following formula (VIIb), which has the following in this order: [ka] (In formula (I), formula (V), formula (VI), formula (VIb), and formula (VIIb), R 1 represents a hydrogen atom or a hydrocarbon group, and R 2 represents a hydrogen atom or a linear alkyl group. 6 represents a substituted or unsubstituted arylmethyl group. 7 represents a linear alkyl group having 1 to 29 carbon atoms. In formula (VIII), X represents a hydroxyl group, an alkoxy group, an alkylcarbonyloxy group, or a halogen atom. <e5>a step of subjecting a compound represented by the following formula (V) to a reduction reaction together with a substituted or unsubstituted arylmethylamine in the presence of a transition metal catalyst or in the presence of an ate complex-type hydride reducing agent, thereby obtaining a compound represented by the following formula (VI); a step of subjecting the compound represented by formula (VI) to a debenzylation reaction to obtain a compound represented by the following formula (VIb); a step of optically resolving the compound represented by formula (VIb) using a chiral organic acid; a step of subjecting the optically resolved compound represented by formula (VIb) and a compound represented by formula (VIII) below to an amidation reaction; A method for producing a compound represented by the following formula (VIIb), which has the following in this order: [ka] (In formula (V), formula (VI), formula (VIb), and formula (VIIb), R 1 represents an alkyl group having 1 to 8 carbon atoms, preferably a methyl group or an ethyl group, and R 2 represents an n-tetradecyl group. 6 represents a substituted or unsubstituted arylmethyl group. 7 represents a linear alkyl group having 1 to 29 carbon atoms. In formula (VIII), X represents a hydroxyl group, an alkoxy group, an alkylcarbonyloxy group, or a halogen atom. <e6>A step of subjecting a compound represented by the following formula (V) to a reduction reaction together with a substituted or unsubstituted arylmethylamine in the presence of borane to obtain a compound represented by the following formula (VI); a step of subjecting the compound represented by formula (VI) to a debenzylation reaction to obtain a compound represented by the following formula (VIb); a step of optically resolving the compound represented by formula (VIb) using a chiral organic acid; a step of subjecting the optically resolved compound represented by formula (VIb) and a compound represented by formula (VIII) below to an amidation reaction; A method for producing a compound represented by the following formula (VIIb), which has the following in this order: [ka] (In formula (V), formula (VI), formula (VIb), and formula (VIIb), R 1 represents an alkyl group having 1 to 8 carbon atoms, preferably a methyl group or an ethyl group, and R 2 represents an n-tetradecyl group. 6 represents a substituted or unsubstituted arylmethyl group. 7 represents a linear alkyl group having 1 to 29 carbon atoms. In formula (VIII), X represents a hydroxyl group, an alkoxy group, an alkylcarbonyloxy group, or a halogen atom. <e7> <b1> ~ <b18>The compound represented by formula (I) is obtained by any one of the production methods described in <e3>The manufacturing method described in <e8> <b1> ~ <b18>The compound represented by formula (I) is obtained by any one of the production methods described in <e4>The manufacturing method described in <e9>In the formula (VII) or (VIIb), R 1 is an alkyl group having 1 to 8 carbon atoms, preferably a methyl group or an ethyl group; <e1> ~ <e8>1. The manufacturing method according to any one of the preceding claims. <e10>In the formula (VII) or (VIIb), R 2 is a hydrogen atom or a linear alkyl group having 1 to 21 carbon atoms, preferably a linear alkyl group having 8 to 18 carbon atoms, more preferably an n-tetradecyl group; <e1> ~ <e9>1. The manufacturing method according to any one of the preceding claims. <e11>In the formula (VII), R 6 is an unsubstituted arylmethyl group, preferably a benzyl group; <e1> ~ <e10>1. The manufacturing method according to any one of the preceding claims. <e12>the arylmethyl group has a substituent, and the substituent is substituted with an aryl group; <e1> ~ <e11>1. The manufacturing method according to any one of the preceding claims. <e13>In the formula (VII) or (VIIb), R 7 is a linear alkyl group having 5 to 23 carbon atoms, preferably a linear alkyl group having 7 to 19 carbon atoms, more preferably a heptadecyl group; <e1> ~ <e12>1. The manufacturing method according to any one of the preceding claims. <e14>In the formula (VIII), R 7 is a linear alkyl group having 5 to 23 carbon atoms, preferably a linear alkyl group having 7 to 19 carbon atoms, more preferably a heptadecyl group; <e1> ~ <e13>1. The manufacturing method according to any one of the preceding claims. <e15>The compound represented by formula (VI) is R 6 is a compound represented by formula (VI), <e1> ~ <e14>1. The manufacturing method according to any one of the preceding claims. <e16>the molar ratio of the compound represented by formula (VIII) to the compound represented by formula (VI) (compound represented by formula (VIII) / compound represented by formula (VI)) is 1.0 or more and 3 or less, preferably 1.0 or more and 2 or less, more preferably 1.0 or more and 1.5 or less; <e1> ~ <e15>1. The manufacturing method according to any one of the preceding claims. <e17>In the formula (VIII), X is a hydroxyl group, and the step of subjecting the compound to an amidation (N-acylation) reaction is carried out in the presence of a condensing agent and a condensation auxiliary. <e1> ~ <e16>1. The manufacturing method according to any one of the preceding claims. <e18>the condensing agent is selected from dicyclohexylcarbodiimide, diisopropylcarbodiimide, and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride; <e17>The manufacturing method described in <e19>the molar ratio of the condensing agent to the compound represented by formula (VIII) (condensing agent / compound represented by formula (VIII)) is 1 or more; <e17>or <e18>The manufacturing method described in <e20>the condensation auxiliary is selected from dimethylaminopyridine, N-methylimidazole, 1-hydroxybenzotriazole, and 1-hydroxy-7-azabenzotriazole; <e17> ~ <e19>1. The manufacturing method according to any one of the preceding claims. <e21>the molar ratio of the condensation auxiliary to the compound represented by formula (VIII) (condensation auxiliary / compound represented by formula (VIII)) is 1 or more; <e17> ~ <e20>1. The manufacturing method according to any one of the preceding claims. <e22>In formula (VIII), X is an alkoxy group, preferably a methoxy group. <e1> ~ <e16>1. The manufacturing method according to any one of the preceding claims. <e23>The step of subjecting the compound to an amidation (N-acylation) reaction is carried out in the presence of a strong base catalyst. <e22>The manufacturing method described in <e24>The strong base catalyst is at least one selected from the group consisting of an alkali metal hydroxide or alkoxide, preferably sodium hydroxide, sodium methoxide, and sodium ethoxide. <e23>The manufacturing method described in <e25>the molar ratio of the strong base catalyst to the compound represented by formula (VIII) (strong base catalyst / carboxylic acid ester) is 0.01 or more; <e23>or <e24>The manufacturing method described in <e26>In the formula (VIII), X is a linear alkylcarbonyloxy group having 1 to 29 carbon atoms. <e1> ~ <e16>1. The manufacturing method according to any one of the preceding claims. <e27>the step of subjecting the compound to an amidation (N-acylation) reaction is carried out in the presence of a basic compound; <e26>The manufacturing method described in <e28>The basic compound is a tertiary amine selected from triethylamine and diethylisopropylamine. <e27>The manufacturing method described in <e29>the molar ratio of the basic compound to the compound represented by formula (VIII) (basic compound / compound represented by formula (VIII)) is 1 or more; <e27>or <e28>The manufacturing method described in <e30>The step of subjecting the compound to an amidation (N-acylation) reaction is carried out in the presence of a catalyst. <e1> ~ <e29>1. The manufacturing method according to any one of the preceding claims. <e31>the catalyst is selected from dimethylaminopyridine, N-methylimidazole, 1-hydroxybenzotriazole, and 1-hydroxy-7-azabenzotriazole; <e30>The manufacturing method described in <e32>the molar ratio of the catalyst to the compound represented by formula (VIII) (catalyst / compound represented by formula (VIII)) is 0.01 or more; <e30>or <e31>The manufacturing method described in <e33>In the formula (VIII), X is a halogen atom, preferably an atom selected from a chlorine atom and a bromine atom, more preferably a chlorine atom. <e1> ~ <e16>1. The manufacturing method according to any one of the preceding claims. <e34>The step of subjecting the compound to an amidation (N-acylation) reaction is carried out in the presence of a basic compound. <e33>The manufacturing method described in <e35>The basic compound is a tertiary amine selected from triethylamine and diethylisopropylamine. <e34>The manufacturing method described in <e36>the molar ratio of the basic compound to the compound represented by formula (VIII) (basic compound / compound represented by formula (VIII)) is 1 or more; <e34>or <e35>The manufacturing method described in <e37>In the step of subjecting the mixture to an amidation (N-acylation) reaction, the reaction temperature is 0°C or higher and 110°C or lower, more preferably 5°C or higher and 105°C or lower, and more preferably 10°C or higher and 100°C or lower. <e1> ~ <e36>1. The manufacturing method according to any one of the preceding claims. <f1> <d1> ~ <d46>A compound represented by formula (VI) prepared by any one of the methods <e1> ~ <e37>A method for producing a compound represented by formula (IX), comprising a step of subjecting at least one compound selected from the compounds represented by formula (VII) produced by any of the methods described above to a deacetalization reaction. [ka] (In formula (VI) and formula (VII), R 1 represents a hydrogen atom or a hydrocarbon group, and R 6 represents a hydrogen atom or a substituted or unsubstituted arylmethyl group. 2 represents a hydrogen atom or a linear alkyl group. 7 represents a linear alkyl group having 1 to 29 carbon atoms. 8 represents a hydrogen atom, a substituted or unsubstituted arylmethyl group, or a linear acyl group having from 1 to 30 carbon atoms. <f2>The compound represented by formula (IX) is any one selected from the group consisting of a compound represented by formula (IX-1) and a compound represented by formula (IX-2): <f1>The manufacturing method described in [ka] [Example]

[0128] In the following examples, various physical properties were measured by the following methods. Compound N (N represents the compound number) means a compound represented by formula (N).

[0129] <Devices used for compound identification and analysis> (Nuclear magnetic resonance device (NMR)) Bruker Ascend NMR 400 (manufactured by Bruker) Chemical shift correction is performed by adding tetramethylsilane (TMS) to the measurement sample. 1 H-NMR shows the protons from TMS ( 1 H) peak was set to the standard of 0.00 ppm. 13 C-NMR shows the carbon ( 13 C) peak was set to a standard of 0.00 ppm. (Gas chromatograph measuring device) Gas chromatograph (GC): Agilent 6850 (Agilent Technologies) Gas chromatograph mass spectrometer (GC-MS): Agilent 5975C (Agilent Technologies) Gas chromatograph column (for standard analysis): Ultra ALLOY-1 MS / HT (Frontier Labs, inner diameter 0.25 mm, film thickness 0.15 μm, length 30 m) Gas chromatograph column (for chiral analysis): CHIRALDEX B-DM (Merck, inner diameter 0.25 mm, film thickness 0.25 μm, length 30 m) The following measurement conditions were used for normal analysis and GC-MS analysis. Carrier gas: Nitrogen, 0.73 mL / min Injection conditions: 250°C, split ratio 1 / 50 Detection conditions: FID method, 300°C Column temperature conditions: 40°C for 3 minutes, then increase the temperature to 350°C at 10°C / min and hold for 16 minutes Internal standard compound: n-dodecane Ionization method: Electron Ionization (EI) method Ion source temperature: 230℃ Interface temperature: 350℃ The following measurement conditions were used for chiral analysis. Carrier gas: Helium, 2.0 mL / min Injection conditions: 180°C, split ratio 1 / 90 Detection conditions: FID method, 300°C Column temperature conditions: Raise from 80°C to 230°C at 3°C / min and hold for 10 minutes

[0130] <Reaction yield> The reaction yields of the products shown in the following examples were determined by quantitative GC analysis using n-dodecane as an internal standard. Calibration curves required for quantitative analysis were prepared using commercially available samples or high-purity samples purified from reaction mixtures by distillation or silica gel column chromatography.

[0131] <Production Example 1> The compound represented by formula (II) was produced by the following method.

[0132] Production Example 1-1 (Production of Compound II-1) Compound II-1 was produced according to the method described in Example 3 of Patent Document 2. In the following formula (II-1) showing compound II-1, Me represents a methyl group.

[0133] [ka]

[0134] Preparation Example 1-2 (Preparation of Compound II-2) Compound II-2 was prepared according to the method described in Example 1 of Patent Document 2.

[0135] [ka]

[0136] Preparation Example 1-3 (Preparation of Compound II-3) 2-Ethyl-1,3-dioxan-5-ol was produced in the same manner as in Production Example 3 of Patent Document 2, except that paraldehyde was replaced with propionaldehyde diethyl acetal (molar ratio to glycerol: 1.0). The obtained 2-ethyl-1,3-dioxan-5-ol was treated in the same manner as in Example 3 of Patent Document 2 to produce compound II-3. In the following formula (II-3) showing compound II-3, Et represents an ethyl group.

[0137] [ka]

[0138] The NMR data of Compound II-3 are shown below. · 1 H-NMR (400 MHz, CDCl3, δ ppm ): 1.00 (3H, t, J=7.6Hz), 1.75 (2H, qd, J=7.6, 5.1Hz), 4.29 (2H, d, J=17.0Hz), 4.40 (2H, d, J=17.0Hz), 4.81 (1H, t, J=5.1Hz). · 13 C-NMR (100 MHz, CDCl, δ ppm ):8.2, 27.3, 72.7, 101.3, 204.8.

[0139] Preparation Example 1-4 (Preparation of Compound II-4) 2-t-Butyl-1,3-dioxan-5-ol was produced in the same manner as in Production Example 1-3, except that propionaldehyde diethyl acetal was replaced with 2,2-dimethylpropionaldehyde. The resulting 2-t-butyl-1,3-dioxan-5-ol was treated in the same manner as in Example 3 of Patent Document 2 to produce Compound II-4. In the following formula (II-4) showing Compound II-4, t-Bu represents a tert-butyl group.

[0140] [ka]

[0141] The NMR data of Compound II-4 are shown below. · 1 H-NMR (400 MHz, CDCl3, δ ppm ): 0.99(9H, s), 4.27(2H, d, J=17.0Hz), 4.43(1H, s), 4.43(2H, d, J=17.0Hz). · 13 C-NMR (100 MHz, CDCl, δ ppm ):24.6, 35.3, 73.4, 105.8, 205.2.

[0142] Preparation Example 1-5 (Preparation of Compound II-5) Compound II-5 was produced according to the method described in Example 2 of Patent Document 2. In the following formula (II-5) showing Compound II-5, Ph represents a phenyl group.

[0143] [ka]

[0144] <Production Example 2> (Production of Compound III-1) A 1 L flask equipped with a 100 mL dropping funnel was charged with 96.2 g of 1-dodecanol, 0.853 g of 4-acetamido-2,2,6,6-tetramethylpiperidine 1-oxyl free radical, 64.3 g of 2,6-dimethylpyridine, and 400 g of 2-butanone, and cooled with stirring under a nitrogen atmosphere. A solution of 39.1 g of trichloroisocyanuric acid in 100 g of 2-butanone was added to the dropping funnel in two portions and added dropwise over 2 hours, adjusting the rate to maintain the reaction temperature within the 0°C to 5°C range. After stirring at the same temperature for 1 hour, 9.00 g of 2-propanol was added and the mixture was stirred for an additional 20 minutes. The reaction was terminated once the excess trichloroisocyanuric acid had been completely consumed. The by-produced powdery solid was filtered off, and 100 g of methyl tert-butyl ether was added to the reaction liquid from which 2-butanone was distilled off. The precipitated powdery solid was filtered off again, and the solvent was distilled off to obtain 91.7 g of an orange oily crude product. Subsequently, 85.0 g of the crude product was transferred to a 200 mL flask equipped with a Claisen tube, a Liebig condenser, and a distillate receiver, and pentadecanal, which was compound III-1, was obtained as a colorless liquid at a distillate temperature of 117 to 121°C under a reduced pressure of 0.13 kPa (absolute pressure).

[0145] [ka]

[0146] The NMR data of compound III-1 are shown below. · 1 H-NMR (400 MHz, CDCl3, δ ppm ): 0.88 (3H, t, J=6.8Hz), 1.24-1.34 (22H, m), 1.63 (2H, tt, J=7.3, 7.2Hz), 2.42 (2H, td, J=7.3, 1.8Hz), 9.76 (1H, t, J=1.8Hz). · 13 C-NMR (100 MHz, CDCl, δ ppm ):14.1, 22.1, 22.7, 29.2, 29.4, 29.4, 29.6, 29.7, 29.7, 31.9, 43.9, 203.0.

[0147] Example 1: Examination of the amount of carboxylic acid used As shown below, the amount of carboxylic acid (acetic acid) used was investigated in the method for obtaining compound I-1 by aldol condensation reaction of compound II-1 and compound III-1. The compounds represented by formula (IV) used in this example were compound IV-1 (L-proline) and compound IV-2 (pyrrolidine).

[0148] [ka]

[0149] Example 1-1 A 30 mL flask was charged with 0.365 g of compound II-1, 0.210 g of compound III-1, 0.105 g of compound IV-1, 0.100 g of the internal standard compound n-dodecane, and 2.50 g of methyl tert-butyl ether, and the mixture was stirred under a nitrogen atmosphere. To this suspension, 2.50 g of acetic acid was added. After confirming that compound IV-1 had dissolved and become a homogeneous solution, the reaction was continued for 3 hours at 20°C to 25°C. Subsequently, 5 mL of saturated aqueous ammonium chloride solution was added to the reaction solution, and the mixture was stirred for an additional 10 minutes. GC analysis of the organic layer revealed that the reaction yield of compound I-1 was 74%. Subsequently, the organic layer was separated into oil and water and the solvent was evaporated to obtain a crude product of compound I-1. The crude product was purified by silica gel column chromatography (developing solvent: n-hexane / ethyl acetate = 20, volume ratio). After the solvent was evaporated, the residue was dried in vacuo to obtain compound I-1 with a purity of 94.7%.

[0150] The NMR data of compound I-1 are shown below. · 1 H-NMR (400 MHz, CDCl3, δ ppm ):0.88(3H, t, J=6.8Hz), 1.23-1.34(22H, m), 1.40-1.45(2H, m), 1.51(3H, d, J=5.2Hz), 2.13-2.19( 2H, m), 4.33 (1H, d, J=18.0Hz), 4.40 (1H, d, J=18.0Hz), 5.18 (1H, q, J=5.2Hz), 5.98 (1H, t, J=7.8Hz). · 13 C-NMR (100 MHz, CDCl, δ ppm ):13.1, 19.4, 21.7, 23.4, 28.3, 28.3, 28.4, 28.6, 28.7, 28.7, 28.7, 30.9, 71.5, 96.4, 118.5, 147.2, 189.5.

[0151] Examples 1-2 to 1-5 Compound I-1 was produced in the same manner as in Example 1-1, except that the amounts of the compound represented by formula (IV), acetic acid used, and reaction time were changed as shown in Table 1. The reaction yield of compound I-1 is shown in Table 1.

[0152] [Table 1]

[0153] Example 2: Examination of reaction solvents As shown below, the influence of the reaction solvent on the reaction yield was examined in the method for obtaining compound I-1 by aldol condensation reaction of compound II-1 and compound III-1.

[0154] Examples 2-1 to 2-11 Compound I-1 was produced in the same manner as in Example 1-1, except that the solvent, the amount of acetic acid used, and the reaction time were changed as shown in Table 2. The reaction yield of compound I-1 is shown in Table 2.

[0155] [Table 2]

[0156] Example 3: Examination of the enantioselectivity of the compound represented by formula (I) As shown below, the enantioselectivity of compound I-1 produced by aldol condensation reaction of compound II-1 and compound III-1 was examined depending on the compound represented by formula (IV). The compounds represented by formula (IV) used were Compound IV-1 and Compound IV-2, as well as the following Compound IV-3 (trans-4-(tert-butyldiphenylsilyloxy)-L-proline), Compound IV-4 (D-prolinamide), Compound IV-5 ((S)-2-(methoxymethyl)pyrrolidine), Compound IV-6 ((S)-1-(2-pyrrolidinylmethyl)pyrrolidine), Compound IV-7 ((R)-3-pyrrolidinol), Compound IV-8 ((R)-3-(tert-butoxycarbonyloxy)pyrrolidine), Compound IV-9 ((3S,4S)-3,4-pyrrolidinediol), Compound IV-10 ((R)-3-(dimethylamino)pyrrolidine), Compound IV-11 ((S)-3-acetamidopyrrolidine), and Compound IV-12 ((R)-3-(tert-butoxycarbonylamino)pyrrolidine).

[0157] [ka]

[0158] Example 3-1 Compound I-1 obtained in Example 1-4 was subjected to gas chromatography using the above chiral column. Because the peaks of both enantiomers partially overlapped, the peaks obtained were calibrated to a 50:50 ratio. Thereafter, the enantioselectivity in the production of compound I-1 was calibrated in the same manner as in this example.

[0159] The absolute configuration of each enantiomer of compound I-1 was determined as follows. First, from compound I-3 (enantiomeric ratio 61:39) obtained in Example 5-2 described later, compound V-3 obtained in Example 6-3 and compound VI-3a (4,5-anti form) obtained in Examples 7-8 were used to obtain an enantiomeric mixture of erythro-dihydrosphingosine (compound IX-1 (erythro form)) in Example 12-2. The absolute configuration of the main component of erythro-dihydrosphingosine obtained in Example 12-2 was determined to be (2R,3S), and the absolute configuration of the by-product was determined to be (2S,3R). These results indicate that the absolute configurations of the main component of compound VI-3a obtained in Example 7-8 were (2R,4S,5R), and the absolute configurations of the by-product were (2S,4R,5S), and that the absolute configurations of the main component of compound I-3 obtained in Example 5-2 were (2R), and (2S), respectively. Based on this result, compound I-3 obtained in Example 5-2 described below under the above conditions was subjected to gas chromatography using a chiral column, and the absolute configuration of each enantiomer of compound I-1 was determined from the obtained peaks.

[0160] Example 3-2 The enantioselectivity in the production of compound I-1 was confirmed in the same manner as in Example 3-1, except that compound I-1 was replaced by compound I-1 obtained in Example 1-1. The results are shown in Table 3.

[0161] Examples 3-3 to 3-12 Compound I-1 was produced in the same manner as in Example 1-1, except that the amounts of compound II-1, the compound represented by formula (IV), and acetic acid used, and the reaction time were changed as shown in Table 3. The reaction yield and enantioselectivity of compound I-1 are shown in Table 3.

[0162] [Table 3]

[0163] Example 4: Examination of conditions for aldol condensation reaction As shown below, conditions for the aldol condensation reaction between Compound II-1 and Compound III-1 were examined.

[0164] Examples 4-1 to 4-11 Compound I-1 was produced in the same manner as in Example 1-1, except that the amount of compound II-1 used, the compound represented by formula (IV) and its amount used, the amount of acetic acid used, and the reaction time were changed as shown in Table 4. The reaction yield of compound I-1 is shown in Table 4.

[0165] [Table 4]

[0166] Example 5: Study of the compound represented by formula (II) As shown below, the enantioselectivity of the compound represented by formula (I) in the aldol condensation reaction of the compound represented by formula (II) with compound III-1 can be evaluated by the following formula: 1 The effects of

[0167] Examples 5-1 to 5-4 Compounds I-2 to I-5 were produced in the same manner as in Examples 4-11, except that the compound represented by formula (II) was changed as shown in Table 5. The reaction yields and enantioselectivities of compounds I-2 to I-5 are shown in Table 5. The enantioselectivity of Compound I-3 and Compound I-4 was determined as follows. First, the racemates of Compound I-3 and Compound I-4 were prepared, and the peaks of both enantiomers were determined by gas chromatography using the chiral column. Since the peaks of both enantiomers partially overlapped, the peaks were calibrated so that the ratio was 50:50. The absolute configuration of compound I-3 obtained in Example 5-2 was determined as described above. In addition, compound I-4 obtained in Example 5-3 was subjected to gas chromatography using a chiral column under the same conditions as in Example 3-1, and the enantioselectivity was determined from the peaks of both enantiomers.

[0168] [ka]

[0169] [Table 5]

[0170] The NMR data of compound I-2 are shown below. · 1 H-NMR (400 MHz, CDCl3, δ ppm ):0.88(3H, t, J=6.9Hz), 1.23-1.35(22H, m), 1.37-1.44(2H, m), 2.17(2H, td, J=7.5, 7.8Hz), 4.46(1H, d , J=18.2Hz), 4.54 (1H, d, J=18.2Hz), 5.20 (1H, d, J=6.3Hz), 5.28 (1H, d, J=6.3Hz), 6.05 (1H, t, J=7.8Hz). · 13 C-NMR (100 MHz, CDCl, δ ppm ):14.1, 22.7, 24.5, 28.4, 29.4, 29.4, 29.6, 29.7, 29.7, 29.7, 31.9, 73.2, 91.2, 120.3, 148.3, 190.2.

[0171] The NMR data of compound I-3 are shown below. · 1 H-NMR (400 MHz, CDCl3, δ ppm ):0.89(3H,t,J=6.8Hz), 1.03(3H,t,J=7.5Hz), 1.23-1.34(22H,m), 1.39-1.44(2H,m), 1.82(2H,qd,J=7.5,5.1Hz ), 2.14-2.19 (2H, m), 4.32 (1H, d, J=18.3Hz), 4.42 (1H, d, J=18.0Hz), 4.95 (1H, t, J=5.1Hz), 5.99 (1H, t, J=7.8Hz). · 13 C-NMR (100MHz, CDCl3, δ) ppm ):8.0, 14.1, 22.7, 24.4, 27.5, 28.4, 29.4, 29.4, 29.4, 29.6, 29.7, 29.7, 29.7, 31.9, 72.6, 101.1, 119.5, 148.3, 190.8.

[0172] The NMR results of Compound I-4 are shown below. · 1 H-NMR (400MHz, CDCl3, δ) ppm ):0.88(3H,t,J=6.8Hz),1.06(9H,s),1.22-1.35(22H,m),1.39-1.45(2H,m),2.14-2.19( 2H, m), 4.29 (1H, d, J=18.2Hz), 4.43 (1H, d, J=18.2Hz), 4.60 (1H, s), 5.97 (1H, t, J=7.9Hz). · 13 C-NMR (100MHz, CDCl3, δ) ppm ):14.1, 22.7, 24.3, 24.4, 28.4, 29.4, 29.4, 29.5, 29.6, 29.7, 29.7, 31.9, 35.1, 72.9, 105.2, 119.0, 148.5, 191.1.

[0173] The NMR results of Compound I-5 are shown below. · 1 H-NMR (400MHz, CDCl3, δ) ppm ):0.88(3H, t, J=6.9Hz), 1.22-1.36(22H, m), 1.41-1.49(2H, m), 2.20-2.25(2H, m), 4.55( 2H, d, J=1.0Hz), 6.01 (1H, s), 6.11 (1H, t, J=7.8Hz), 7.41-7.44 (3H, m), 7.55-7.58 (2H, m). · 13 C-NMR (100 MHz, CDCl, δ ppm ):14.1, 22.7, 24.6, 28.4, 29.4, 29.4, 29.6, 29.7, 29.7, 29.7, 31.9, 72.7, 99.1, 120.7, 126.2, 128.5, 129.5, 136.3, 148.3, 190.1.

[0174] Example 6: Preparation of compound represented by formula (V) The compound represented by formula (V) was produced by the following method.

[0175] Example 6-1 (Preparation of Compound V-2) A 120 mL pressure-resistant glass vessel fitted to the inside of an autoclave reactor was charged with 2.97 g of compound I-2, 0.833 g of a 5%-palladium carbon catalyst (Kawaken Fine Chemicals, PH type, 53% water content), 0.511 g of the internal standard compound n-dodecane, and 15.0 g of 2-propanol. The atmosphere was purged with nitrogen gas and hydrogen gas three times each, after which hydrogen was introduced into the autoclave reactor at a hydrogen gauge pressure of 0.4 MPa and the reaction was carried out at 50 °C for 2 hours. After filtering the catalyst from the reaction solution, the filtrate was analyzed by GC, and the reaction yield of compound V-2 was 98%. Subsequently, after a portion of 2-propanol was distilled off, Compound V-2 was purified by recrystallization to obtain Compound V-2 with a purity of 97.5%.

[0176] [ka]

[0177] The NMR data of compound V-2 are shown below. · 1 H-NMR (400 MHz, CDCl3, δ ppm ):0.88(3H, t, J=6.9Hz), 1.21-1.32(24H, m), 1.39-1.46(2H, m), 1.70-1.79(1H, m), 1.85-1.91(1H, m), 4.21(1H, ddd, J =0.9, 4.0, 8.2Hz), 4.27(1H, dd, J=0.9, 17.4Hz), 4.34(1H, d, J=17.4Hz), 4.98(1H, d, J=6.0Hz), 5.13(1H, d, J=6.0Hz). · 13 C-NMR (100 MHz, CDCl, δ ppm ):14.1, 22.7, 24.9, 29.3, 29.4, 29.4, 29.6, 29.6, 29.7, 29.7, 29.8, 72.7, 82.9, 91.1, 206.1.

[0178] Examples 6-2 and 6-3 (Preparation of Compounds V-1 and V-3) Compounds V-1 and V-3 were produced in the same manner as in Example 6-1, except that the compound represented by formula (I) and the reaction temperature were changed as shown in Table 6, and purification was performed by silica gel chromatography. The reaction yields and diastereoselectivities of compounds V-1 and V-3 are shown in Table 6. In Table 6, the diastereoselectivities of compounds V-1 and V-3 are shown as the ratio of the syn isomer (hereinafter also referred to as "2,4-syn isomer") to the anti isomer (hereinafter also referred to as "2,4-anti isomer") in the configuration of the alkyl group at the 2-position and the alkyl group at the 4-position (2,4-syn isomer:2,4-anti isomer). The configuration was determined as the 2,4-syn isomer when an NOE correlation was confirmed between the protons at the 2- and 4-positions.

[0179] [ka]

[0180] [Table 6]

[0181] The NMR data of compound V-1 (2,4-syn form) are shown below. · 1 H-NMR (400 MHz, CDCl3, δ ppm ):0.88(3H, t, J=6.9Hz), 1.23-1.32(24H, m), 1.39-1.46(2H, m), 1.43(3H, d, J=5.0Hz), 1.66-1.75(1H, m), 1.84-1.93(1H, m) , 4.20 (1H, dddd, J=0.8, 1.2, 4.0, 7.7Hz), 4.25 (1H, dd, J=1.2, 17.5Hz), 4.33 (1H, dd, J=0.8, 17.5Hz), 5.11 (1H, q, J=5.0Hz). · 13 C-NMR (100 MHz, CDCl, δ ppm ):14.1, 20.5, 22.7, 24.9, 29.4, 29.4, 29.4, 29.6, 29.6, 29.7, 29.7, 30.0, 31.9, 72.2, 82.9, 97.5, 206.4.

[0182] The NMR data of compound V-3 (2,4-syn form) are shown below. · 1 H-NMR (400 MHz, CDCl3, δ ppm ): 0.88 (3H, t, J=6.9Hz), 0.99 (3H, t, J=7.5Hz), 1.22-1.32 (24H, m), 1.39-1.46 (2H, m), 1.67-1.77 (1H, m), 1.73 (2H, qd, J=7.5, 5.2Hz), 1.8 6-1.94(1H, m), 4.18(1H, dddd, J=0.9, 1.2, 4.0, 7.9Hz), 4.24(1H, dd, J=1.2, 17.5Hz), 4.34(1H, dd, J=0.9, 17.5Hz), 4.85(1H, t, J=5.2Hz). · 13 C-NMR (100 MHz, CDCl, δ ppm ):8.5, 14.3, 22.8, 25.0, 27.6, 29.5, 29.6, 29.7, 29.8, 29.8, 29.8, 30.1, 32.1, 72.5, 83.0, 101.6, 206.8.

[0183] Example 7: Preparation of the compound represented by formula (VI) The compound represented by formula (VI) was produced by the following method.

[0184] Example 7-1 (Production of Compound VI-2a (4,5-anti form)) A 30 mL flask was charged with 100 mg of compound V-2, 61.3 mg of ammonium trifluoroacetate, 64.6 mg of acetic acid, 68.2 mg of the internal standard compound n-dodecane, and 4.0 g of methanol, and the mixture was stirred at 50 °C under a nitrogen atmosphere. 52.7 mg of 2-picoline borane was added to the solution, and the reaction was continued at 50 °C for 2 hours. 1 mL of 2N aqueous hydrochloric acid and 4 mL of saturated saline were added to the reaction solution, and the mixture was stirred for 5 minutes. After distilling off the methanol, saturated aqueous sodium carbonate was added until the pH of the aqueous layer reached 12, and the mixture was extracted with methyl tert-butyl ether. GC analysis of the organic layer revealed that the reaction yield of compound VI-2a was 29%. Next, 450 mg of a strong acid cation exchange resin (Organo Corporation, trademark Amberlyst, 15JWET type) was added to the organic layer, and the mixture was stirred at 20 to 25°C for 3 hours. 10 mL of methyl tert-butyl ether and 10 mL of 1N aqueous sodium hydroxide solution were added to the filtered ion exchange resin, and the mixture was stirred again at 20 to 25°C for 3 hours. The ion exchange resin was filtered, and the organic layer, which had been separated into oil and water, was evaporated and then dried in vacuo to obtain compound VI-2a with a purity of 89.2%.

[0185] [ka]

[0186] The NMR data of Compound VI-2a (4,5-anti form) are shown below. · 1 H-NMR (400 MHz, CDCl3, δ ppm ):0.88(3H, t, J=6.9Hz), 1.24-1.34(26H, m), 1.45-1.58(1H, m), 1.52(2H, br), 1.77-1.85(1H, m), 2.71(1H, ddd, J=4.9, 9.0, 10.4Hz), 3.1 2(1H, dd, J=2.4, 8.9, 9.0Hz), 3.18(1H, dd, J=10.4, 10.8Hz), 3.98(1H, dd, J=4.9, 10.8Hz), 4.59(1H, d, J=6.1Hz), 5.03(1H, d, J=6.1Hz). · 13 C-NMR (100 MHz, CDCl, δ ppm ):14.3, 22.8, 25.1, 29.5, 29.7, 29.7, 29.7, 29.8, 29.8, 29.8, 31.9, 32.1, 49.4, 72.6, 83.7, 93.5.

[0187] Examples 7-2 to 7-9 (Preparation of Compounds VI-1a to VI-3a) Compounds VI-1a to VI-3a were produced in the same manner as in Example 7-1, except that the compound represented by formula (V), ammonia equivalent and its amount used, reducing agent and its amount used, hydrogenation catalyst and its amount used, acid and its amount used, solvent, reaction temperature, and reaction time were changed as shown in Table 7. The reaction yields of Compounds VI-1a to VI-3a and the diastereoselectivities of Compounds VI-1a to VI-3a are shown in Table 7. However, ammonium formate used in Examples 7-3, 7-7, and 7-9 was used as the ammonia equivalent and reducing agent. In Table 7, the diastereoselectivity of compounds VI-1a to VI-3a is shown as the ratio of the conformation of the alkyl group at the 4th position and the amino group at the 5th position in the syn form (hereinafter also referred to as "4,5-syn form") to the anti form (hereinafter also referred to as "4,5-anti form") (4,5-syn form:4,5-anti form) for each compound obtained by trimethylsilylating the amino group of compounds VI-1a to VI-3a. The conformation of the 4th and 5th positions of compounds VI-1a to VI-3a was determined by comparing compound IX-1 (erythro-dihydrosphingosine) produced from compound VI-3a with a known stereochemical standard, as described above, and 1 The coupling constants were determined from H-NMR.

[0188] [ka]

[0189] The NMR data of Compound VI-2a (4,5-syn form) are shown below. · 1 H-NMR (400 MHz, CDCl3, δ ppm ):0.88(3H, t, J=6.9Hz), 1.23-1.34(26H, m), 1.36-1.47(2H, m), 1.63(2H, br), 2.57(1H, ddd, J=1.4, 1.6, 2.0Hz), 3.60(1H, ddd , J=1.6, 5.2, 8.0Hz), 3.83(1H, dd, J=2.0, 11.3Hz), 3.98(1H, dd, J=1.4, 11.3Hz), 4.71(1H, d, J=6.1Hz), 5.03(1H, d, J=6.1Hz). · 13 C-NMR (100 MHz, CDCl, δ ppm ):14.1, 22.7, 25.0, 29.4, 29.6, 29.6, 29.7, 29.7, 29.7, 31.8, 31.9, 48.7, 73.8, 79.7, 94.3.

[0190] The NMR data of Compound VI-1a (4,5-anti form) are shown below. · 1 H-NMR (400 MHz, CDCl3, δ ppm ): 0.88(3H, t, J=6.8Hz), 1.21-1.38(26H, m), 1.33(3H, d, J=5.2Hz), 1.44-1.57(1H, m), 1.60(2H, br), 1.77-1.84(1H, m), 3.29(1H, ddd, J= 5.0, 9.5, 10.2Hz), 3.35 (1H, dd, J=10.2, 10.6Hz), 3.47 (1H, ddd, J=4.9, 9.5, 9.5Hz), 4.10 (1H, dd, J=5.0, 10.6Hz), 4.66 (1H, q, J=5.2Hz). · 13 C-NMR (100MHz, CDCl3, δ) ppm ):14.1, 20.5, 22.7, 25.1, 29.4, 29.6, 29.6, 29.7, 29.7, 29.7, 31.8, 31.9, 66.0, 70.9, 81.5, 98.9.

[0191] The NMR results of Compound VI-1a (4,5-Semer) are shown below. · 1 H-NMR (400MHz, CDCl3, δ) ppm ):0.88(3H,t,J=6.8Hz),1.24-1.32(26H,m),1.33(3H,d,J=5.1Hz),1.37-1.48(1H,m),1.53-1.62(3H,m),2.51(1H,ddd,J=1.6,1 .6, 1.9Hz), 3.63 (1H, ddd, J=1.6, 5.9, 7.5Hz), 3.87 (1H, dd, J=1.9, 11.4Hz), 3.96 (1H, dd, J=1.6, 11.4Hz), 4.71 (1H, q, J=5.1Hz). · 13 C-NMR (100MHz, CDCl3, δ) ppm ):14.1, 22.1, 22.7, 25.0, 29.4, 29.6, 29.6, 29.6, 29.7, 29.7, 31.8, 31.9, 47.6, 73.7, 79.5, 99.5.

[0192] The NMR results of compound VI-3a (4,5-aminomeric compound) are shown below. · 1 H-NMR (400MHz, CDCl3, δ) ppm ):0.88(3H,t,J=6.8Hz), 0.93(3H,t,J=7.6Hz), 1.25-1.32(26H,m), 1.39-1.55(3H,m), 1.59-1.65(3H,m), 2.65(1H,ddd,J=5.1,9. 3, 10.1Hz), 3.12 (1H, ddd, J=2.4, 9.1, 9.3Hz), 3.22 (1H, dd, J=10.1, 11.2Hz), 4.06 (1H, dd, J=5.1, 11.2Hz), 4.40 (1H, t, J=5.3Hz). · 13 C-NMR (100MHz, CDCl3, δ) ppm ):8.8, 14.3, 22.8, 25.3, 27.9, 29.5, 29.7, 29.8, 29.8, 29.8, 32.0, 32.1, 49.1, 72.6, 83.3, 103.1.

[0193] The NMR data of Compound VI-3a (4,5-syn form) are shown below. · 1 H-NMR (400 MHz, CDCl3, δ ppm ): 0.88(3H, t, J=6.8Hz), 0.94(3H, t, J=7.5Hz), 1.23-1.34(26H, m), 1.37-1.45(1H, m), 1.57-1.68(5H, m), 2.51(1H, ddd, J=1.5, 1 .7, 1.7Hz), 3.61(1H, ddd, J=1.7, 5.5, 7.6Hz), 3.86(1H, dd, J=1.7, 11.3Hz), 3.97(1H, dd, J=1.5, 11.3Hz), 4.47(1H, t, J=5.2Hz). · 13 C-NMR (100 MHz, CDCl, δ ppm ):8.4, 14.3, 22.8, 25.2, 27.3, 28.1, 29.5, 29.7, 29.7, 29.8, 29.8, 31.9, 32.1, 48.1, 73.8, 79.6, 103.7.

[0194] [Table 7]

[0195] Example 8: Preparation of the compound represented by formula (VI) The compound represented by formula (VI) was prepared by the following method using benzylamine as an ammonia equivalent.

[0196] Example 8-1 (Production of Compound VI-2b (4,5-syn-isomer)) Compound VI-2b was produced in the same manner as in Example 7-1, except that ammonium trifluoroacetate was replaced with benzylamine and the amount of acetic acid used was changed as shown in Table 8. In the following structural formula showing Compound VI-2b, Bn represents a benzyl group.

[0197]

change

[0198] The NMR data of Compound VI-2b (4,5-Semer) is shown below. · 1 H-NMR (400MHz, CDCl3, δ) ppm ):0.88(3H,t,J=6.8Hz),1.23-1.33(26H,m),1.46-1.56(1H,m),1.60-1.75(2H , m), 2.34 (1H, ddd, J=1.4, 1.5, 1.9Hz), 3.58 (1H, dd, J=1.5, 11.6Hz), 3.59 (1H, t d, J=6.8, 1.9Hz), 3.73 (1H, d, J=13.5Hz), 4.03 (1H, d, J=13.5Hz), 4.24 (1H, dd, J =1.4, 11.6Hz), 4.72 (1H, d, J=6.0Hz), 5.03 (1H, d, J=6.0Hz), 7.21-7.32 (5H, m). · 13 C-NMR (100MHz, CDCl3, δ) ppm ):14.3, 22.8, 25.1, 29.5, 29.7, 29.8, 29.8, 29.8, 31.7, 32.1, 50.8, 53.3, 68.2, 80.8, 94.5, 127.0, 128.3, 128.4, 140.8.

[0199] Examples 8-2~8-6 (Production of Compounds VI-1b~VI-3b) Compounds VI-1b to VI-3b were produced in the same manner as in Example 8-1, except that the compound represented by formula (V), the amount of benzylamine used, the reducing agent, and the hydrogenation catalyst were changed as shown in Table 8. The reaction yields of Compounds VI-1b to VI-3b and the diastereoselectivities of Compounds VI-1b to VI-3b are shown in Table 8. In Table 8, the diastereoselectivities of Compounds VI-1b to VI-3b are shown as the ratio of the syn isomer (hereinafter also referred to as "4,5-syn isomer") to the anti isomer (hereinafter also referred to as "4,5-anti isomer") in terms of the configuration of the alkyl group at the 4th position and the benzylamino group at the 5th position (4,5-syn isomer:4,5-anti isomer).

[0200] [ka]

[0201] The NMR data of Compound VI-1b (4,5-anti form) are shown below. · 1 H-NMR (400 MHz, CDCl3, δ ppm ): 0.88 (3H, t, J=6.8Hz), 1.23-1.31 (26H, m), 1.31 (3H, d, J=5.1Hz), 1.40-1. 52(2H, m), 1.76-1.84(1H, m), 2.57(1H, ddd, J=4.8, 9.9, 9.9Hz), 3.24-3.30(1 H, m), 3.27 (1H, dd, J=9.9, 10.9Hz), 3.71 (1H, d, J=13.1Hz), 3.83 (1H, d, J=13. 1Hz), 4.19 (1H, dd, J=4.8, 10.9Hz), 4.63 (1H, q, J=5.1Hz), 7.22-7.34 (5H, m). · 13 C-NMR (100 MHz, CDCl, δ ppm ):14.3, 20.9, 22.8, 25.2, 29.5, 29.8, 29.8, 29.8, 29.9, 32.0, 32.1, 52.0, 54.2, 71.1, 81.5, 98.9, 127.0, 128.2, 128.6, 140.4.

[0202] The NMR data of Compound VI-1b (4,5-syn form) are shown below. · 1 H-NMR (400MHz, CDCl3, δ) ppm ):0.88(3H, t, J=6.8Hz), 1.23-1.32(26H, m), 1.32(3H, d, J=5.1Hz), 1.39-1. 52(1H,m),1.64-1.70(2H,m),2.27(1H,ddd,J=1.5,1.5,1.8Hz),3.59-3.63(1 H, m), 3.60 (1H, dd, J=1.5, 11.6Hz), 3.71 (1H, d, J=13.5Hz), 4.02 (1H, d, J=13. 5Hz), 4.24 (1H, dd, J=1.5, 11.6Hz), 4.72 (1H, q, J=5.1Hz), 7.22-7.39 (5H, m). · 13 C-NMR (100MHz, CDCl3, δ) ppm ):14.3, 21.2, 22.8, 25.1, 29.5, 29.7, 29.7, 29.8, 29.8, 29.8, 31.7, 32.0, 50.7, 52.1, 68.0, 80.7, 99.7, 126.9, 128.3, 128.6, 140.8.

[0203] The NMR results of compound VI-3b (4,5-aminomeric compound) are shown below. · 1 H-NMR (400MHz, CDCl3, δ) ppm ):0.88(3H,t,J=6.8Hz), 0.93(3H,t,J=7.5Hz), 1.24-1.32(26H,m), 1.40-1.5 3(2H, m), 1.61(2H, qd, J=7.5, 5.3Hz), 1.77-1.85(1H, m), 2.56(1H, ddd, J=4.9 , 9.5, 10.3Hz), 3.22-3.29 (2H, m), 3.75 (1H, d, J=13.1Hz), 3.83 (1H, d, J=13.1 Hz), 4.20 (1H, dd, J=4.9, 10.9Hz), 4.38 (1H, t, J=5.3Hz), 7.23-7.35 (5H, m)). · 13 C-NMR (100MHz, CDCl3, δ) ppm ):8.8, 14.3, 22.8, 25.2, 28.0, 29.5, 29.8, 29.8, 29.8, 29.9, 32.1, 32.2, 52.0, 54.7, 71.1, 81.4, 103.0, 127.3, 128.2, 128.6, 140.5.

[0204] The NMR data of Compound VI-3b (4,5-syn form) are shown below. · 1 H-NMR (400 MHz, CDCl3, δ ppm ): 0.88 (3H, t, J=6.8Hz), 0.93 (3H, t, J=7.5Hz), 1.24-1.32 (26H, m), 1.58-1 .71(5H, m), 2.28(1H, ddd, J=1.5, 1.5, 1.8Hz), 3.60(1H, td, J=5.8, 1.8Hz), 3.60(1H, dd, J=1.5, 11.6Hz), 3.71(1H, d, J=13.5Hz), 4.02(1H, d, J=13.5Hz ), 4.26 (1H, dd, J=1.5, 11.6Hz), 4.48 (1H, t, J=5.2Hz), 7.20-7.40 (5H, m)). · 13 C-NMR (100 MHz, CDCl, δ ppm ):8.5, 14.3, 22.8, 25.2, 28.2, 29.5, 29.8, 29.8, 29.8, 29.8, 29.8, 31.7, 32.1, 50.7, 52.1, 68.1, 80.7, 103.8, 126.9, 128.3, 128.3, 141.0.

[0205] [Table 8]

[0206] Example 9: Debenzylation reaction of the compound represented by formula (VI) The benzyl group was removed (debenzylation) from the compound represented by formula (VI) prepared in Example 8 by the method shown below.

[0207] Example 9-1 (Production of Compound VI-2a (4,5-syn-isomer)) A 120 mL pressure-resistant glass vessel fitted to the interior of an autoclave reaction apparatus was charged with 2.85 g of compound VI-2b (4,5-syn-isomer) obtained in Example 8-1, 0.202 g of 20% palladium hydroxide carbon catalyst (Kawaken Fine Chemicals, 51% water content), 0.105 g of n-dodecane (internal standard compound), and 15.0 g of 2-propanol. The atmosphere was purged with nitrogen gas and hydrogen gas three times each, and then hydrogen was introduced into the autoclave reaction apparatus at a hydrogen gauge pressure of 0.4 MPa. The reaction was carried out at 50° C. for 2 hours. After filtering the catalyst from the reaction solution, the filtrate was analyzed by GC, and the reaction yield of compound VI-2a was 98%.

[0208] Examples 9-2 and 9-3 (Preparation of Compounds VI-1a (4,5-syn-isomer) and VI-3a (4,5-syn-isomer)) Compounds VI-1a (4,5-syn isomer) and VI-3a (4,5-syn isomer) were prepared in the same manner as in Example 9-1, except that the compound represented by formula (VI), solvent, and reaction temperature were changed as shown in Table 9. The reaction yields of compounds VI-1a (4,5-syn isomer) and VI-3a (4,5-syn isomer) are shown in Table 9.

[0209] [Table 9]

[0210] Example 10: Optical resolution of the compound represented by formula (VI) A 100 mL flask was charged with 1.00 g of compound VI-1a (4,5-syn: 2R,4S,5S; 2S,4R,5R) obtained in Example 7-7 (61:39 ratio), 0.549 g of L-tartaric acid, 20 mL of methanol, 20 mL of ethanol, and 20 mL of water, and heated to 50 °C to form a homogeneous solution. After cooling to 20-25 °C and allowing to stand for 2 hours, the precipitated powdery solid was filtered and suspended in methyl tert-butyl ether. Saturated aqueous sodium carbonate was added to the aqueous layer until the pH reached 12, and compound VI-1a (2S,4R,5R) was extracted from the organic layer with an enantiomeric excess (ee) of 94%. The recovery of compound VI-1a (2S,4R,5R) was 68%.

[0211] Example 11: Preparation of compound represented by formula (VII) A compound represented by formula (VII) was produced from a compound represented by formula (VI) by the method shown below.

[0212] Example 11-1 (Production of Compound VII-1 (4,5-syn-isomer)) A 30 mL flask was charged with 0.177 g of octadecanoic acid, 0.119 g of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride, 0.098 g of 1-hydroxybenzotriazole monohydrate, 0.163 g of diisopropylethylamine, and 5 g of tetrahydrofuran, and the mixture was stirred at 20 to 25 ° C. To this mixture was added a solution of 0.200 g of compound VI-1a prepared in Example 10-1 in 3 g of tetrahydrofuran, and the reaction was continued for 6 hours at 20 to 25 ° C. The reaction solution was extracted with 10 g of methyl tert-butyl ether and 10 g of saturated aqueous sodium chloride solution. After distilling off the solvent from the organic layer, the mixture was recrystallized from n-hexane to obtain compound VII-1 (4,5-syn-isomer) in an isolated yield of 62%.

[0213] [ka]

[0214] The NMR data of Compound VII-1 (4,5-syn form) are shown below. · 1 H-NMR (400 MHz, CDCl3, δ ppm ): 0.88(6H, t, J=6.8Hz), 1.25-1.33(52H, m), 1.35(3H, d, J=5.1Hz), 1.38-1.52(3H, m), 1.59-1.71(3H, m), 2.24(2H, td, J=7. 5, 2.0Hz), 3.70-3.74(1H, m), 3.85(1H, dd, J=1.8, 11.7Hz), 3.92-3.96(2H, m), 4.75(1H, q, J=5.1Hz), 6.10(1H, d, J=9.5Hz). · 13 C-NMR (100 MHz, CDCl, δ ppm ):14.1, 21.0, 22.7, 24.7, 25.9, 29.3, 29.4, 29.4, 29.5, 29.5, 29.6, 29.6, 29.7, 29.7, 31.7, 31.9, 36.9, 45.2, 71.4, 78.9, 99.8, 172.9.

[0215] Example 11-2 (Preparation of Compound VII-3 (4,5-anti form)) In Example 11-1, compound VII-3 (4,5-anti isomer) was obtained in an isolation yield of 60% in the same manner as in Example 11-1, except that compound VI-1a (4,5-syn isomer) was replaced with compound VI-3a (4,5-anti isomer) prepared in Example 7-8.

[0216] [ka]

[0217] The NMR data of compound VII-3 (4,5-anti form) are shown below. · 1 H-NMR (400 MHz, CDCl3, δ ppm ): 0.88 (6H, t, J=6.8Hz), 0.93 (3H, t, J=7.5Hz), 1.23-1.33 (52H, m), 1.46-1.58 (3H, m), 1.60-1.67 (5H, m), 2.15 (2H, td, J=7.5, 2.5Hz), 3.28 -3.32(1H, m), 3.29(1H, dd, J=10.7, 10.7Hz), 3.89-3.97(1H, m), 4.11(1H, dd, J=5.2, 10.7Hz), 4.39(1H, t, J=5.2Hz), 5.05(1H, d, J=9.3Hz). · 13 C-NMR (100 MHz, CDCl, δ ppm ):8.6, 14.3, 22.8, 25.3, 25.9, 27.8, 29.4, 29.5, 29.7, 29.7, 29.8, 29.8, 29.8, 29.9, 32.1, 32.2, 37.1, 46.7, 69.4, 80.2, 103.1, 173.0.

[0218] Example 12: Preparation of compound represented by formula (IX) A compound represented by formula (IX) was produced from a compound represented by formula (VI) by the method shown below.

[0219] Example 12-1 (Production of threo-dihydrosphingosine) A 30 mL flask equipped with a condenser was charged with 0.256 g of compound VI-3a (4,5-syn-isomer) prepared in Example 7-9, 0.864 g of 85% phosphoric acid, 4.44 g of 1-butanol, and 0.270 g of water. The reaction was continued for 10 hours under reflux at atmospheric pressure. 20 g of methyl tert-butyl ether and 20 g of 1 mol / L aqueous sodium hydroxide were added to the reaction mixture, and the organic layer was extracted. The insoluble components in the organic layer were separated from the aqueous layer, and the solvent was evaporated and dried under vacuum at 60 °C to obtain a light brown solid. 5 g of ethanol and 0.5 g of water were added, and the mixture was sonicated. The insoluble components were collected by filtration, washed sequentially with ethanol, water, and n-hexane, and then dried under vacuum to obtain compound IX-1 (threo-dihydrosphingosine) in 44% isolation yield.

[0220] [ka]

[0221] The NMR data of compound IX-1 (threo form) are shown below. · 1 H-NMR (400MHz, Pyridine-d5, δ ppm ):0.88(3H, t, J=6.8Hz), 1.23-1.45(26H, m), 1.53-1.64(1H, m), 1.74-1.92(3H, m), 3.17(1H, ddd, J=4.2, 5.0, 6.7Hz), 4.01-4.07(2H, m), 4.16(1H, dd, J=5.0, 10.4Hz), 5.76(1H, br), 6.21(1H, br). · 13 C-NMR(100MHz, Pyridine-d5, δ ppm ):14.4, 23.0, 26.8, 29.7, 30.0, 30.1, 30.2, 30.3, 32.2, 35.2, 58.2, 65.6, 71.9.

[0222] Example 12-2 (Production of erythro-dihydrosphingosine) In Example 12-1, compound IX-1 (erythro-dihydrosphingosine) was obtained in an isolation yield of 65% in the same manner as in Example 12-1, except that compound VI-1a (4,5-syn form) was replaced with compound VI-3a (4,5-anti form) prepared in Example 7-8. As described above, the absolute configuration of the main component of the obtained erythro-dihydrosphingosine was determined to be (2R,3S), and the absolute configuration of the by-product was determined to be (2S,3R).

[0223] [ka]

[0224] The NMR data of compound IX-1 (erythro form) are shown below. · 1 H-NMR (400MHz, Pyridine-d5, δ ppm ):0.88(3H, t, J=6.8Hz), 1.23-1.47(26H, m), 1.54-1.67(1H, m), 1.79-1.92(3H, m), 3.31(1H, ddd, J=4.5, 5.6, 7.2Hz), 4.00-4.04(1H, m), 4.11(1H, dd, J=7.3, 10.4Hz), 4.31(1H, dd, J=4.4, 10.4Hz), 5.99(1H, br). · 13 C-NMR(100MHz, Pyridine-d5, δ ppm ):14.4, 23.0, 26.7, 29.7, 30.0, 30.1, 30.2, 30.3, 32.2, 34.4, 58.6, 65.0, 74.1.

[0225] Example 12-3 (Production of erythro-ceramide NDS) In Example 12-1, compound VI-1a (4,5-syn form) was replaced with compound VII-3 (4,5-anti form) prepared in Example 11-2, and 1-butanol was replaced with 2-butanol. In the same manner as in Example 12-1, compound X-1 (erythro-ceramide NDS) was obtained in an isolation yield of 76%.

[0226] [ka]

[0227] The NMR data of compound X-1 (erythro form) are shown below. · 1 H-NMR (400MHz, Pyridine-d5, δ ppm ):0.88(6H, t, J=6.7Hz), 1.23-1.47(52H, m), 1.56-1.67(1H, m), 1.80-2.05(5H, m), 2.52(2H, td, J=7.4, 2.0Hz), 4. 30-4.38(2H, m), 4.49-4.54(1H, m), 4.68-4.71(1H, m), 6.38(1H, d, J=6.2Hz), 6.49(1H, br), 8.50(1H, d, J=8.6Hz). · 13 C-NMR(100MHz, Pyridine-d5, δ ppm ):14.4, 23.0, 26.6, 26.6, 29.7, 29.8, 29.9, 30.0, 30.0, 30.1, 30.2, 30.3, 32.2, 35.2, 37.0, 56.7, 62.5, 72.2, 173.5. [Industrial Applicability]

[0228] According to the present invention, a 4-alkylidene-1,3-dioxan-5-one useful as a synthetic intermediate for various compounds such as sphingoid bases and ceramides can be provided. Furthermore, a method for producing a 4-alkylidene-1,3-dioxan-5-one using an aldehyde-type dioxanone as a raw material can be provided. The 4-alkylidene-1,3-dioxan-5-one obtained by the present invention is an important intermediate for various useful compounds and is suitable for use as a raw material for pharmaceuticals, cosmetics, and chemicals, such as sphingoid bases and ceramides. < / e1> < / d1> < / f1> < / e1> < / e1> < / e1> < / e1> < / e1> < / e17> < / e17> < / e1> < / e1> < / e1> < / e1> < / e1> < / e1> < / e1> < / e1> < / e1> < / b1> < / e8> < / b1> < / e7> < / d1> < / e1> < / d39> < / d39> < / d39> < / d1> < / d38> < / d31> < / d31> < / d31> < / d1> < / d31> < / d1> < / d1> < / d1> < / d1> < / d21> < / d1> < / d13> < / d13> < / d13> < / d1> < / d2> < / d1> < / d1> < / d1> < / d1> < / c1> < / d2> < / c1> < / c1> < / c1> < / c1> < / b1> < / c1> < / b1> < / b1> < / b1> < / b1> < / b1> < / b1> < / b1> < / b1> < / b1> < / b1> < / b1> < / b1> < / b1> < / a1> < / a1> < / a1>

Claims

1. A compound represented by the following formula (I): 【Chemistry 1】 (In formula (I), R 1 represents a hydrogen atom, an alkyl group having from 1 to 8 carbon atoms, or a phenyl or naphthyl group which may be substituted with an alkyl group selected from a methyl group and an ethyl group; R 2 represents a hydrogen atom or a linear alkyl group.

2. In formula (I), R 2 The compound according to claim 1, wherein is a linear alkyl group having from 8 to 18 carbon atoms.

3. In formula (I), R 1 is an alkyl group having 1 to 4 carbon atoms, and R 2 The compound according to claim 1 or 2, wherein is an n-tetradecyl group.

4. A method for producing a compound represented by the following formula (I), comprising a step of subjecting a compound represented by the following formula (II) and a compound represented by the following formula (III) to an aldol condensation reaction in the presence of a compound represented by the following formula (IV): 【Chemistry 2】 (In formula (I), formula (II), and formula (III), R 1 represents a hydrogen atom, an alkyl group having from 1 to 8 carbon atoms, or a phenyl or naphthyl group which may be substituted with an alkyl group selected from a methyl group and an ethyl group; R 2 represents a hydrogen atom or a linear alkyl group. 3 , R 4 , and R 5 each independently represents a group selected from a hydrogen atom, a hydroxyl group, an alkoxy group, an N,N-dialkylamino group, an alkoxymethyl group, an N,N-dialkylaminomethyl group, a carboxy group, a carbamoyl group, an acyloxy group, an acylamino group, a silyloxy group, an alkoxycarbonyloxy group, and an alkoxycarbonylamino group.

5. The method according to claim 4 , wherein the step of subjecting the compound to an aldol condensation reaction is carried out in the presence of a carboxylic acid.

6. In the formula (IV), R 3 is a hydrogen atom, and R 4 and R 5 at least one of which is selected from the group consisting of a hydroxyl group, an alkoxy group, an N,N-dialkylamino group, an alkoxymethyl group, an N,N-dialkylaminomethyl group, a carboxy group, a carbamoyl group, an acyloxy group, an acylamino group, a silyloxy group, an alkoxycarbonyloxy group, and an alkoxycarbonylamino group.

7. In the formula (I), R 1 is a phenyl group or naphthyl group optionally substituted with an alkyl group having from 1 to 8 carbon atoms, or an alkyl group selected from a methyl group and an ethyl group, and the enantiomeric excess of the compound represented by formula (IV) is 90% ee or more.

8. In the formula (I) and the formula (II), R 1 is an alkyl group having 1 to 8 carbon atoms, In the formula (I) and the formula (III), R 2 is an n-tetradecyl group, In the formula (IV), R 3 is a hydrogen atom, and R 4 and R 5 and each independently represent at least one selected from the group consisting of a hydroxyl group, an alkoxy group, an N,N-dialkylamino group, an acylamino group, an alkoxycarbonyloxy group, and an alkoxycarbonylamino group.

9. A step of subjecting a compound represented by the following formula (I) to a hydrogenation reaction to obtain a compound represented by the following formula (V): a step of subjecting the compound represented by formula (V) to a reduction reaction together with an ammonia equivalent in the presence of a transition metal catalyst or in the presence of an ate complex type hydride reducing agent; and the ate complex hydride reducing agent is at least one selected from the group consisting of sodium borohydride, sodium triacetoxyborohydride, and sodium cyanoborohydride; the ammonia equivalent is at least one selected from the group consisting of ammonia, an ammonium salt of a carboxylic acid, a substituted or unsubstituted arylmethylamine, and a disilazane; A method for producing a compound represented by the following formula (VI): 【Transformation 3】 (In formula (I), formula (V), and formula (VI), R 1 represents a hydrogen atom, an alkyl group having from 1 to 8 carbon atoms, or a phenyl or naphthyl group which may be substituted with an alkyl group selected from a methyl group and an ethyl group; R 2 represents a hydrogen atom or a linear alkyl group. 6 represents a hydrogen atom or a substituted or unsubstituted arylmethyl group.

10. A step of subjecting a compound represented by the following formula (I) to a hydrogenation reaction to obtain a compound represented by the following formula (V): a step of subjecting the compound represented by formula (V) to a reduction reaction together with an ammonia equivalent in the presence of borane; and the ammonia equivalent is at least one selected from the group consisting of ammonia, an ammonium salt of a carboxylic acid, a substituted or unsubstituted arylmethylamine, and a disilazane; A method for producing a compound represented by the following formula (VI): 【Chemistry 4】 (In formula (I), formula (V), and formula (VI), R 1 represents a hydrogen atom, an alkyl group having from 1 to 8 carbon atoms, or a phenyl or naphthyl group which may be substituted with an alkyl group selected from a methyl group and an ethyl group; R 2 represents a hydrogen atom or a linear alkyl group. 6 represents a hydrogen atom or a substituted or unsubstituted arylmethyl group.

11. The method according to claim 9 , further comprising a step of optically resolving the compound represented by formula (VI).

12. The method according to claim 11 , wherein the optical resolution is carried out using a chiral organic acid.

13. A step of subjecting a compound represented by the following formula (I) to a hydrogenation reaction to obtain a compound represented by the following formula (V): a step of subjecting the compound represented by formula (V) to a reduction reaction together with an ammonia equivalent in the presence of a transition metal catalyst or in the presence of an ate complex type hydride reducing agent to obtain a compound represented by the following formula (VI); a step of optically resolving the compound represented by formula (VI) using a chiral organic acid; and the ate complex hydride reducing agent is at least one selected from the group consisting of sodium borohydride, sodium triacetoxyborohydride, and sodium cyanoborohydride; The ammonia equivalent is at least one selected from the group consisting of ammonia, an ammonium salt of a carboxylic acid, a substituted or unsubstituted arylmethylamine, and a disilazane. A method for producing a compound represented by the following formula (VI): 【Transformation 5】 (In formula (I), formula (V), and formula (VI), R 1 represents a hydrogen atom, an alkyl group having from 1 to 8 carbon atoms, or a phenyl or naphthyl group which may be substituted with an alkyl group selected from a methyl group and an ethyl group; R 2 represents a hydrogen atom or a linear alkyl group. 6 represents a hydrogen atom or a substituted or unsubstituted arylmethyl group.

14. A step of subjecting a compound represented by the following formula (I) to a hydrogenation reaction to obtain a compound represented by the following formula (V): a step of subjecting the compound represented by formula (V) to a reduction reaction together with an ammonia equivalent in the presence of borane to obtain a compound represented by the following formula (VI); a step of optically resolving the compound represented by formula (VI) using a chiral organic acid; and the ammonia equivalent is at least one selected from the group consisting of ammonia, an ammonium salt of a carboxylic acid, a substituted or unsubstituted arylmethylamine, and a disilazane; A method for producing a compound represented by the following formula (VI): 【Transformation 6】 (In formula (I), formula (V), and formula (VI), R 1 represents a hydrogen atom, an alkyl group having from 1 to 8 carbon atoms, or a phenyl or naphthyl group which may be substituted with an alkyl group selected from a methyl group and an ethyl group; R 2 represents a hydrogen atom or a linear alkyl group. 6 represents a hydrogen atom or a substituted or unsubstituted arylmethyl group.

15. In the formula (VI), R 6 The method according to claim 13, wherein when is a substituted or unsubstituted arylmethyl group, the method further comprises a step of subjecting the compound represented by formula (VI) to a debenzylation reaction.

16. A step of subjecting a compound represented by the following formula (I) to a hydrogenation reaction to obtain a compound represented by the following formula (V): a step of subjecting the compound represented by formula (V) to a reduction reaction together with a substituted or unsubstituted arylmethylamine in the presence of a transition metal catalyst or in the presence of an ate complex-type hydride reducing agent to obtain a compound represented by formula (VI): a step of subjecting the compound represented by formula (VI) to a debenzylation reaction to obtain a compound represented by formula (VIb): a step of optically resolving the compound represented by formula (VIb) using a chiral organic acid; a step of subjecting the optically resolved compound represented by formula (VIb) and a compound represented by formula (VIII) below to an amidation reaction; in that order, a method for producing a compound represented by the following formula (VIIb), wherein the ate complex-type hydride reducing agent is at least one selected from the group consisting of sodium borohydride, sodium triacetoxyborohydride, and sodium cyanoborohydride: 【Transformation 7】 (In formula (I), formula (V), formula (VI), formula (VIb), and formula (VIIb), R 1 represents a hydrogen atom, an alkyl group having from 1 to 8 carbon atoms, or a phenyl or naphthyl group which may be substituted with an alkyl group selected from a methyl group and an ethyl group; R 2 represents a hydrogen atom or a linear alkyl group. 6 represents a substituted or unsubstituted arylmethyl group. 7 represents a linear alkyl group having 1 to 29 carbon atoms. In formula (VIII), X represents a hydroxyl group, an alkoxy group, an alkylcarbonyloxy group, or a halogen atom.

17. A step of subjecting a compound represented by the following formula (I) to a hydrogenation reaction to obtain a compound represented by the following formula (V): a step of subjecting the compound represented by formula (V) to a reduction reaction together with a substituted or unsubstituted arylmethylamine in the presence of borane to obtain a compound represented by the following formula (VI); a step of subjecting the compound represented by formula (VI) to a debenzylation reaction to obtain a compound represented by formula (VIb): a step of optically resolving the compound represented by formula (VIb) using a chiral organic acid; a step of subjecting the optically resolved compound represented by formula (VIb) and a compound represented by formula (VIII) below to an amidation reaction; A method for producing a compound represented by the following formula (VIIb): 【Transformation 8】 (In formula (I), formula (V), formula (VI), formula (VIb), and formula (VIIb), R 1 represents a hydrogen atom, an alkyl group having from 1 to 8 carbon atoms, or a phenyl or naphthyl group which may be substituted with an alkyl group selected from a methyl group and an ethyl group; R 2 represents a hydrogen atom or a linear alkyl group. 6 represents a substituted or unsubstituted arylmethyl group. 7 represents a linear alkyl group having 1 to 29 carbon atoms. In formula (VIII), X represents a hydroxyl group, an alkoxy group, an alkylcarbonyloxy group, or a halogen atom.

18. The method according to claim 16, wherein the compound represented by formula (I) is obtained by the method according to any one of claims 4 to 8.

19. The method according to claim 17, wherein the compound represented by formula (I) is obtained by the method according to any one of claims 4 to 8.

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