JP4799892B2 - Cyclohexane derivative and method for producing the same - Google Patents

Description

  The present invention relates to a crystal of (1R, 2R) -1,2-bis (methanesulfonyloxymethyl) cyclohexane or an enantiomer thereof useful as a pharmaceutical and agrochemical intermediate, and a method for producing the same.

で表される（１Ｒ，２Ｒ）−１，２−ビス（メタンスルホニルオキシメチル）シクロヘキサン又はその対掌体（以下、化合物（１）と称する場合がある）は、例えば、特許文献１に記載の向精神性物質とし有用なイミド誘導体の中間体等、医農薬中間体として有用な化合物である。
化合物（１）の製造方法としては、例えば、式（２）

で表される（１Ｒ，２Ｒ）−１，２−シクロヘキサンジメタノール又はその対掌体（以下、化合物（２）と称する場合がある）にメタンスルホン化試剤を反応させて、化合物（１）を含む粗生成物を得たのち、粗生成物のメタノール溶液から結晶化することにより結晶として得る方法（例えば、非特許文献１、非特許文献２、非特許文献３）、粗生成物、トルエン及びイソプロピルエーテルの混合溶液から結晶化することにより結晶として得る方法（例えば、特許文献２）などが知られている。 Formula (1)

(1R, 2R) -1,2-bis (methanesulfonyloxymethyl) cyclohexane or an enantiomer thereof (hereinafter sometimes referred to as compound (1)) represented by, for example, It is a compound useful as an intermediate for medicines and agricultural chemicals, such as an intermediate of an imide derivative useful as a psychotropic substance.
As a manufacturing method of compound (1), for example, formula (2)

(1R, 2R) -1,2-cyclohexanedimethanol or an enantiomer thereof (hereinafter sometimes referred to as compound (2)) is reacted with a methanesulfonate reagent to give compound (1). After obtaining a crude product containing, a method of obtaining a crystal by crystallization from a methanol solution of the crude product (for example, Non-Patent Document 1, Non-Patent Document 2, Non-Patent Document 3), crude product, toluene and A method of obtaining a crystal by crystallization from a mixed solution of isopropyl ether (for example, Patent Document 2) is known.

Japanese Patent Laid-Open No. 5-17440 JP 2004-224664 A [0025] (Example 7) Chemistry of Material, vol. 13, 1665-1673, 2001 Journal of Organic Chemistry, vol 61, pp. 700-709, 1996 Journal of Chemical Society (J. Chem. Soc.), 389-398, 1953

However, the crystals of compound (1) obtained by these methods are needle-like crystals, and the crystals obtained by drying the crystals have a bulk density of about 0.2 g / ml. Therefore, there has been a demand for a crystal of compound (1) that can be easily prepared.
An object of the present invention is to provide a crystal of the compound (1) that has a high bulk density after drying, is difficult to powder, and is easy to handle, and a method for producing the crystal.

で表される（１Ｒ，２Ｒ）−１，２−ビス（メタンスルホニルオキシメチル）シクロヘキサン又はその対掌体の結晶、 In the powder X-ray diffraction diagram, the present invention is 12.2 ° ± 0.2 °, 17.9 ° ± 0.2 °, 21.0 ° ± 0.2 °, 19.8 ° ± 0.2 °. Which gives an X-ray diffraction diagram having a peak at 21.0 ° ± 0.2 ° and the highest peak intensity (1)

A crystal of (1R, 2R) -1,2-bis (methanesulfonyloxymethyl) cyclohexane represented by the formula:

  (1R, 2R) -1,2-bis (methanesulfonyloxymethyl) cyclohexane represented by the above formula (1) having a bulk density of 0.6 to 0.8 g / ml, or an enantiomer thereof, and

  The crude product containing (1R, 2R) -1,2-bis (methanesulfonyloxymethyl) cyclohexane represented by the formula (1) or an enantiomer thereof is selected from the group consisting of an ester solvent and a ketone solvent. It is a method for producing a crystal of (1R, 2R) -1,2-bis (methanesulfonyloxymethyl) cyclohexane or an enantiomer thereof, wherein the crystal is dissolved in at least one organic solvent and crystallized.

  Among the production methods of the present invention, a method in which a crude product is dissolved in the organic solvent and then mixed with a hydrocarbon solvent for crystallization tends to reduce the temperature at which crystals are precipitated. It is preferable because there is.

  The crystal of (1R, 2R) -1,2-bis (methanesulfonyloxymethyl) cyclohexane or its enantiomer of the present invention is a crystal that has a high bulk density after drying, is difficult to powder, and is easy to handle. . The manufacturing method is excellent in yield and can be easily manufactured.

Hereinafter, the present invention will be described in detail.
The crystal of (1R, 2R) -1,2-bis (methanesulfonyloxymethyl) cyclohexane or its enantiomer represented by the formula (1), that is, the crystal of the compound (1) includes the compound (1). It can be obtained by crystallization from a mixed solution of a crude product and an organic solvent.
The crude product containing the compound (1) is described in, for example, the methods described in Non-Patent Documents 1 to 3, as well as the tetrahedron asymmetry (Tetrahedron: Asymmetry, vol. 8, pages 987-990, 1997). Methods, methods described in Liebigs Annalen der Chemie (1540-1548, 1980), methods described in Organic Synthesis Collective Volume (Vol. 6, page 482), etc. Can be obtained.

Specifically, (1R, 2R) -1,2-bis (hydroxymethyl) cyclohexane represented by the formula (2) or an enantiomer thereof, that is, a method of reacting the compound (2) with a methanesulfonated reagent, etc. Is exemplified. Below, reaction of a compound (2) and a methane sulfonation reagent is demonstrated.

Examples of the methane sulfonation reagent include halogenated methane sulfonic acids such as chloromethane sulfonic acid, fluorinated methane sulfonic acid, and bromomethane sulfonic acid, such as methane sulfonic anhydride. Preference is given to methanesulfonic acid chloride.
As the usage-amount of a methane sulfonation reagent, it is about 1-5 mol with respect to 1 mol of compound (2), Preferably it is about 2-3 mol.

The reaction with the methane sulfonation reagent is preferably carried out in the presence of a base. Examples of the base used in this reaction include trialkylamines such as triethylamine and diisopropylethylamine, pyridine compounds such as pyridine, lutidine, and picoline, such as quinoline, imidazole, N-methylpyrrolidine, and 1,5-diazabicyclo. [4.3.0] non-5-ene, 1,4-diazabicyclo [2.2.2] octane, 1,8-diazabicyclo [5.4.0] undec-7-ene and the like. . Trialkylamines such as triethylamine are preferable.
The amount of the base to be used is about 1 to 5 mol, preferably about 2 to 4 mol, per 1 mol of compound (2).

Examples of the solvent used for the reaction with the methanesulfonated reagent include 8 or less carbon atoms such as methyl acetate, ethyl acetate, n-butyl acetate, sec-butyl acetate, tert-butyl acetate, and ethyl propionate. Ester solvents, for example, ketone solvents having 8 or less carbon atoms such as 4-methyl-2-pentanone, acetone, methyl ethyl ketone; ether solvents such as dioxane, diethyl ether, tetrahydrofuran, etc., for example, methylene chloride, chloroform, 1, 2 -Halogenated hydrocarbon solvents such as dichloroethane, for example, aromatic hydrocarbon solvents such as benzene, toluene and monochlorobenzene.
Ethyl acetate is preferably used as the ester solvent, and 4-methyl-2-pentanone is preferably used as the ketone solvent.
As the usage-amount of a solvent, it is about 1-50 weight times with respect to a compound (2), Preferably, it is about 1-20 weight times.

The reaction with the methanesulfonated reagent is usually a method in which the compound (2), the methanesulfonated reagent, and preferably the base are stirred under cooling or warming, preferably at about −10 to 50 ° C.
The reaction solution thus obtained is a solution containing the compound (1) and may be used as a crude product as it is, but is preferably washed with water to remove salts and the like produced by the reaction with the methanesulfonated reagent, and then dehydrated. The solution obtained by the above operation is defined as a crude product. Furthermore, you may use what has the crystal | crystallization of the compound (1) which distilled off the solvent as a main component as a crude product. The crude product may contain acicular compound (1).
If the organic solvent described later and the solvent used for the reaction with the methanesulfonated reagent are the same, the reaction solution may be used as a crude product as it is without distilling off the solvent.

Next, a method for producing (1R, 2R) -1,2-bis (methanesulfonyloxymethyl) cyclohexane represented by the formula (1) or an enantiomer thereof, that is, a crystal of the compound (1) will be described.
The method for producing a crystal of compound (1) is a method in which the above crude product is dissolved in at least one organic solvent selected from the group consisting of an ester solvent and a ketone solvent and crystallized.

Examples of the organic solvent used in the method for producing a crystal of the compound (1) include an ester solvent having 8 or less carbon atoms exemplified by the reaction with the methanesulfonated reagent, and a ketone solvent having 8 or less carbon atoms. Ethyl acetate is preferably used as the solvent, and 4-methyl-2-pentanone is preferably used as the ketone solvent.
The amount of the organic solvent to be used varies depending on the type of the organic solvent, but is about 0.3 to 50 times by weight, preferably about 0.3 to 20 times by weight with respect to the compound (1).

As a specific method for obtaining a crystal of compound (1), for example, (I) a crude product is mixed with an organic solvent, diluted and dissolved, and then 30 ° C. or higher, preferably 50 ° C. or higher, particularly preferably 50 A method of precipitating the crystal of compound (1) while distilling off the solvent at about ~ 70 ° C; (II) After mixing and diluting and dissolving the organic solvent in the crude product, 30 ° C or higher, preferably , A method in which a solvent having low solubility such as a hydrocarbon solvent is added at 50 ° C. or higher, particularly preferably about 50 to 70 ° C., to precipitate a crystal of compound (1); (III) An organic solvent is mixed with the crude product After diluting and dissolving, adding a hydrocarbon solvent and heating and dissolving, add as little hydrocarbon solvent as possible at 30 ° C or higher, preferably 50 ° C or higher, particularly preferably about 50 to 70 ° C. Crystallize After, a method of increasing the amount of crystals obtained with cooling to give compound (1). In addition, the post-process after mixing and diluting and dissolving the organic solvent in the crude product may be performed by combining the illustrations of the post-processes (I) to (III). That is, after depositing crystals at 30 ° C. or higher, preferably 50 ° C. or higher, particularly preferably about 50 to 70 ° C., the amount of crystals is increased by combining distillation of solvent or cooling. You may let them.
Among them, it is preferable to cool the crystal after it is precipitated at 50 ° C. or higher, preferably about 50 to 70 ° C., and in particular, a crystal obtained by cooling at about −10 to 10 ° C. This is preferable because the amount of the acid tends to increase.

Among these, (III) is preferable. In particular, a method of adding a hydrocarbon solvent to precipitate crystals at 50 ° C. or higher and then cooling to increase the amount of crystals yields crystals of the compound (1) of the present invention. This is preferable because the temperature range tends to be wide.
Specifically, when about 25% by weight of an organic solvent is mixed with a hydrocarbon solvent to precipitate a crystal, the crystal is crystallized in the range of 40 to 70 ° C. before cooling and then cooled. Therefore, when a hydrocarbon solvent is mixed with about 50% by weight of an organic solvent to precipitate a crystal, the crystal is crystallized in the range of 20 to 70 ° C. before cooling and then cooled. Therefore, when a hydrocarbon solvent is mixed with about 75% by weight of an organic solvent to precipitate a crystal, the crystal is crystallized in the range of 10 to 70 ° C. before cooling and then cooled. Become.

Here, as the hydrocarbon solvent, for example, a linear saturated hydrocarbon having 8 or less carbon atoms such as n-pentane, n-hexane, n-heptane, n-octane, etc., for example, 2-methylpentane, Linear saturated hydrocarbon having 8 or less carbon atoms substituted with an alkyl group such as 2-methylbutane, for example, aromatic carbonization such as benzene, toluene, ortho-xylene, meta-xylene, para-xylene Hydrogen is mentioned. Among these, a linear saturated hydrocarbon which may be substituted with an alkyl group is preferable, and n-heptane is particularly preferable.
The amount of the hydrocarbon solvent used varies depending on the type of the hydrocarbon solvent and the type of the organic solvent, but is usually about 1 to 50 times by weight, preferably about 1 to 20 times by weight with respect to the compound (1). is there.

  The solution containing the crystal of compound (1) obtained by the above method is separated by solid-liquid separation means such as filtration and centrifugation, and further, if necessary, by a method such as reduced pressure drying, ventilation drying, freeze drying and the like. By drying, a crystal of the compound (1) of the present invention can be obtained.

で表される（１Ｒ，２Ｒ）−１，２−ビス（メタンスルホニルオキシメチル）シクロヘキサン又はその対掌体の結晶である。 The crystal of the compound (1) of the present invention is 12.2 ° ± 0.2 °, 17.9 ° ± 0.2 °, 21.0 ° ± 0.2 °, 19. Formula (1) characterized by giving an X-ray diffraction diagram having a peak at 8 ° ± 0.2 ° and the highest peak intensity of 21.0 ° ± 0.2 °

(1R, 2R) -1,2-bis (methanesulfonyloxymethyl) cyclohexane or an enantiomer thereof.

  The crystal of the compound (1) of the present invention usually shows the diffraction angle (2θ) and relative intensity described in Table 1 in the powder X-ray diffraction diagram.

The crystal of the compound (1) of the present invention is usually a columnar crystal having a bulk density of about 0.6 to 0.8 g / ml, and has a higher bulk density and less powdering than conventional needle-like crystals. Excellent handling during transportation.
The bulk density is measured as follows.
(A) Weigh accurately the crystals and gradually add so that the mouth of the graduated cylinder is not blocked. The crystal weight W charged in the measuring cylinder is measured.
(A) After all the crystals have been charged, the brush is used to drop the crystals attached to the funnel into a measuring cylinder.
(C) Flatten the surface of the sample in the graduated cylinder with a spatula so as not to compress the crystal layer, and measure the volume V1.
(D) The bulk density is obtained by the following formula.
Bulk density (g / ml) = Crystal weight W (g) / Volume V1 (ml)

  The melting point of the compound (1) of the present invention is usually 84 to 87 ° C.

EXAMPLES Next, although an Example is given and this invention is demonstrated further more concretely, this invention is not limited at all by these.
(Comparative Example 1)
Methanesulfonyl chloride (5.75 g) was added to a solution of (1R, 2R) -1,2-bis (hydroxymethyl) cyclohexane (2.63 g) in 4-methyl-2-pentanone (154 g), and triethylamine (20.degree. 5.31 g) was added, and the mixture was kept at 20 ° C. for 2 hours. Subsequently, after washing with water and brine, the obtained organic layer was dried over sodium sulfate, and then the organic layer was concentrated under reduced pressure to obtain (1R, 2R) -1,2-bis (methanesulfonyloxymethyl) cyclohexane. About 73 g of residue was obtained. Diisopropyl ether (32 g) was added dropwise to the residue (73 g) at 25 ° C. The mixture was kept at the same temperature for 1 hour, cooled to 3 ° C., and kept at the same temperature for 1 hour. The slurry was filtered, and the obtained crystals were washed with diisopropyl ether (32 g) and dried under reduced pressure to give 4.8 g of ((1R, 2R) -1,2-bis (methanesulfonyloxymethyl) cyclohexane crystals (yield). 87%).
The obtained crystal was an acicular crystal having a bulk density of 0.20 g / ml. When the obtained crystal was subjected to X-ray diffraction measurement using an X-ray of Cu—Kα wavelength (measuring device: RINT2500V, Rigaku Denki Co., Ltd., X-ray: Cu—Kα), the powder X-ray diffraction diagram of FIG. 2 was obtained. It was.
The infrared absorption spectrum (IR) of the obtained crystal is shown in FIG.

(Comparative Example 2)
Methanol (40 g) was added to 8 g of needle-shaped crystals of ((1R, 2R) -1,2-bis (methanesulfonyloxymethyl) cyclohexane prepared by the same method as in Comparative Example 1 and refluxed to dissolve the crystals. The solution was cooled to 0-5 ° C. over about 3 hours and stirred for 1 hour at the same temperature, the slurry was filtered, and the resulting crystals were washed with methanol (20 g) cooled to 0-5 ° C. By drying under reduced pressure, 6.27 g (yield 78%) of ((1R, 2R) -1,2-bis (methanesulfonyloxymethyl) cyclohexane crystals were obtained.
The obtained crystal was an acicular crystal having a bulk density of 0.20 g / ml. The powder X-ray diffraction pattern of the obtained crystals was the same as FIG.
Further, the infrared absorption spectrum (IR) of the obtained crystal was the same as in FIG.

(Comparative Example 3)
A solution of (100 g) in 4 g of needle-like crystals of ((1R, 2R) -1,2-bis (methanesulfonyloxymethyl) cyclohexane prepared by the same method as in Comparative Example 1 was added at room temperature (about 20-25 ° C. ) In an open system for 3 weeks, the amount of the solution became about 62 g, the slurry was filtered, and the obtained crystals were washed with methanol (10 g) and dried under reduced pressure to ((1R, 2R) 1.58 g (yield 40%) of crystals of -1,2-bis (methanesulfonyloxymethyl) cyclohexane were obtained.
The obtained crystal was a needle-like crystal having a bulk density of 0.18 g / ml. The powder X-ray diffraction pattern of the obtained crystals was the same as FIG.
Further, the infrared absorption spectrum (IR) of the obtained crystal was the same as in FIG.

Example 1
10 g of acicular crystals of ((1R, 2R) -1,2-bis (methanesulfonyloxymethyl) cyclohexane prepared by the same method as in Comparative Example 1 was used as a crude product, and the crude product was ethyl acetate (8 g). The solution was heated to 70 ° C. and cooled to 20 ° C. over 1.5 hours, and the slurry was filtered and dried under reduced pressure to give (1R, 2R) -1,2-bis (methanesulfonyloxymethyl) cyclohexane. Of 9.5 g (95% yield from (1R, 2R) -1,2-bis (hydroxymethyl) cyclohexane).
The obtained crystal was a columnar crystal having a bulk density of 0.64 g / ml. When the obtained crystal is subjected to X-ray diffraction measurement using Cu-Kα wavelength X-rays, the powder X-ray diffraction diagram of FIG. 1 is obtained, which shows that Table 1 is satisfied.
The infrared absorption spectrum (IR) of the obtained crystal is shown in FIG.
The melting point was 84-87 ° C.

¹ H-NMR (300 MHz, CDCl ₃ ) of crystals of (1R, 2R) -1,2-bis (methanesulfonyloxymethyl) cyclohexane δ: 1.28-1.40 (4H, m), 1.65 1.89 (6H, m), 3.04 (6H, s), 4.18 (2H, m), 4.29 (2H, m)

(Example 2)
10 g of acicular crystals of ((1R, 2R) -1,2-bis (methanesulfonyloxymethyl) cyclohexane prepared by the same method as in Comparative Example 1 was used as a crude product, and ethyl acetate (40 g) was used as the crude product. The mixture was heated to 55 ° C. to obtain a solution, and n-heptane (40 g) was added dropwise at about 50 minutes at the same temperature, after stirring at 55 ° C. for 1 hour, about 0 to 5 ° C. After cooling at 0 to 5 ° C. for 1.5 hours, the slurry was filtered, and the crystals obtained were mixed with an ethyl acetate / n-heptane mixture (10 g) at a weight ratio of 1: 1. The crystals were washed and dried under reduced pressure to obtain 9.2 g (yield 92%) of (1R, 2R) -1,2-bis (methanesulfonyloxymethyl) cyclohexane crystals.
The obtained crystals were columnar crystals with a bulk density of 0.65 g / ml. The powder X-ray diffraction pattern of the obtained crystals was the same as in FIG.
Further, the infrared absorption spectrum (IR) of the obtained crystal was the same as in FIG.

(Example 3)
Methanesulfonyl chloride (17.2 g) was added to a solution of (1R, 2R) -1,2-bis (hydroxymethyl) cyclohexane (10 g) in ethyl acetate (90 g), and triethylamine (16.0 g) was added at 20 ° C. for 1 hour. Then, the mixture was kept warm at 20 ° C. for 3 hours. Subsequently, after washing with water and brine, the obtained organic layer was dried over sodium sulfate, and then the organic layer was concentrated under reduced pressure to obtain (1R, 2R) -1,2-bis (methanesulfonyloxymethyl) cyclohexane. About 66 g of a crude product containing was obtained.
The obtained crude product was added dropwise with n-heptane (40 g) at 55 ° C. over 1 hour. After keeping at the same temperature for 1 hour, it was cooled to 3 ° C. in about 3 hours, and kept at the same temperature for 1 hour. The slurry was filtered, and the obtained crystals were washed with n-heptane (40 g) and dried under reduced pressure to give 19.1 g (yield) of (1R, 2R) -1,2-bis (methanesulfonyloxymethyl) cyclohexane crystals. 95%).
The obtained crystal was a columnar crystal having a bulk density of 0.68 g / ml. The powder X-ray diffraction pattern of the obtained crystals was the same as in FIG.
Further, the infrared absorption spectrum (IR) of the obtained crystal was the same as in FIG.

Example 4
17.5 g of needle-like crystals of ((1R, 2R) -1,2-bis (methanesulfonyloxymethyl) cyclohexane prepared by the same method as in Comparative Example 1 was used as a crude product, and 4-methyl was added to the crude product. In addition to 2-pentanone (10 g), the solution was heated to 70 ° C. to obtain a solution, cooled to 25 ° C. over 2 hours, the slurry was filtered, and the resulting crystals were washed with 4-methyl-2-pentanone (5 g). Then, 14.3 g (yield 82%) of crystals of (1R, 2R) -1,2-bis (methanesulfonyloxymethyl) cyclohexane were obtained by drying under reduced pressure.
The obtained crystal was a columnar crystal having a bulk density of 0.72 g / ml. The powder X-ray diffraction pattern of the obtained crystals was the same as in FIG.
Further, the infrared absorption spectrum (IR) of the obtained crystal was the same as in FIG.

(Example 5)
10 g of acicular crystals of ((1R, 2R) -1,2-bis (methanesulfonyloxymethyl) cyclohexane prepared by the same method as in Comparative Example 1 was used as a crude product, and 4-methyl-2 was added to the crude product. N-Heptane (20 g) was added to the pentanone (20 g) solution at 50-55 ° C. After stirring for 1 hour at 50-55 ° C., the mixture was cooled to 5 ° C. over about 4 hours. The obtained crystals were washed with n-heptane (20 g) and dried under reduced pressure to give 9.5 g (yield 95%) of (1R, 2R) -1,2-bis (methanesulfonyloxymethyl) cyclohexane crystals. Got.
The obtained crystal was a columnar crystal having a bulk density of 0.70 g / ml. The powder X-ray diffraction pattern of the obtained crystals was the same as in FIG.
Further, the infrared absorption spectrum (IR) of the obtained crystal was the same as in FIG.

(Example 6)
Triethylamine (88.2 g) was added to a solution of (1R, 2R) -1,2-bis (hydroxymethyl) cyclohexane (54.6 g) in 4-methyl-2-pentanone (510 g), and methanesulfonyl chloride (20 ° C.) was added. 95.5 g) was added, and the mixture was kept at 20 ° C. for 2 hours. Subsequently, after sequentially washing with 5% by weight potassium bicarbonate and water, the obtained organic layer was concentrated under reduced pressure, and a crude product containing (1R, 2R) -1,2-bis (methanesulfonyloxymethyl) cyclohexane was obtained. About 262 g of product was obtained.
N-Heptane (219 g) was added dropwise to the obtained crude product at 50 to 55 ° C. After keeping at the same temperature for 1 hour, it was cooled to 5 ° C. in about 4 hours and kept at the same temperature for 1 hour. The slurry was filtered, and the obtained crystals were washed with n-heptane (219 g) and dried under reduced pressure to give 100 g of (1R, 2R) -1,2-bis (methanesulfonyloxymethyl) cyclohexane crystals (yield 87 %).
The obtained crystal was a columnar crystal having a bulk density of 0.74 g / ml. The powder X-ray diffraction pattern of the obtained crystals was the same as in FIG.
Further, the infrared absorption spectrum (IR) of the obtained crystal was the same as in FIG.

  The (1R, 2R) -1,2-bis (methanesulfonyloxymethyl) cyclohexane or the enantiomer of the present invention can be used as an intermediate for medicines and agricultural chemicals such as an intermediate of an imide derivative useful as a psychotropic substance. it can.

2 is a powder X-ray diffraction pattern of (1R, 2R) -1,2-bis (methanesulfonyloxymethyl) cyclohexane obtained in Example 1. FIG. 2 is a powder X-ray diffraction pattern of (1R, 2R) -1,2-bis (methanesulfonyloxymethyl) cyclohexane obtained in Comparative Example 1. FIG. 2 is an infrared absorption spectrum of (1R, 2R) -1,2-bis (methanesulfonyloxymethyl) cyclohexane obtained in Example 1. 2 is an infrared absorption spectrum of (1R, 2R) -1,2-bis (methanesulfonyloxymethyl) cyclohexane obtained in Comparative Example 1.

Claims (7)

In the powder X-ray diffraction pattern, there are peaks at 12.2 ° ± 0.2 °, 17.9 ° ± 0.2 °, 21.0 ° ± 0.2 °, 19.8 ° ± 0.2 °. And an X-ray diffraction pattern having the highest peak intensity of 21.0 ° ± 0.2 ° is given (1)

(1R, 2R) -1,2-bis (methanesulfonyloxymethyl) cyclohexane represented by the formula: Table 1 in the powder X-ray diffraction pattern

2. The crystal according to claim 1, wherein the crystal has a diffraction angle (2θ) and a relative intensity. The crystal according to claim 1 or 2, having a bulk density of 0.6 to 0.8 g / ml. Formula (1)

Or a crude product containing (1R, 2R) -1,2-bis (methanesulfonyloxymethyl) cyclohexane or an enantiomer thereof represented by the formula: at least one organic compound selected from the group consisting of ester solvents and ketone solvents The method for producing a crystal according to any one of claims 1 to 3 , wherein the crystal is dissolved in a solvent and crystallized.   5. The production method according to claim 4, wherein the crude product is dissolved in an organic solvent, and then a hydrocarbon solvent is further mixed to start precipitation of crystals.   6. The production method according to claim 4 or 5, wherein crystallization is performed at 50 ° C. or higher from a solution containing the crude product and the organic solvent.   7. The crude product according to claim 4, wherein (1R, 2R) -1,2-bis (hydroxymethyl) cyclohexane or a product obtained by reacting an enantiomer thereof with a methanesulfonated reagent is used. Manufacturing method.

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