Patent Description:
Sucralose-<NUM>-acetate is one of the important intermediates for producing sucralose, and the purity of sucralose-<NUM>-acetate is one of the keys affecting the yield of sucralose. It is found that, when the purity of sucralose-<NUM>-acetate is <NUM>%, the yield of sucralose after deacylation is <NUM>%; but when the purity of sucralose-<NUM>-acetate is increased to <NUM>%, the yield of sucralose is accordingly increased to <NUM>%. Therefore, the improvement of the purity of sucralose-<NUM>-acetate makes it possible to effectively improve the yield of sucralose. At present, ethyl acetate, butyl acetate and water are widely used industrially for the purification of sucralose-<NUM>-acetate, and the purification of sucralose-<NUM>-acetate is generally achieved by multiple recrystallization.

There are patent reports on the purification of sucralose-<NUM>-acetate. Chinese patent <CIT> discloses a method for purifying sucralose-<NUM>-acetate by recrystallization with ethyl acetate and water, which is a previous sucralose-<NUM>-acetate purification technology used in industry, and has the advantages of high single-pass yield, but the disadvantages of low product purity, multiple recrystallization, and large solvent consumption.

Chinese patent <CIT> discloses a method for purifying sucralose-<NUM>-acetate, including: first preparing a sucralose-<NUM>-acetate crude product into an aqueous solution, and then subjecting the aqueous solution to extraction with ethyl acetate or butyl acetate, concentration, and multiple recrystallization by the above solvent, to obtain a sucralose-<NUM>-acetate crystal. However, the above method has the disadvantages of large organic solvent consumption, low product purity, and poor purification and separation effect.

Chinese patent <CIT> discloses a method for extracting sucralose-<NUM>-ethyl ester, which comprises: after a chlorination stage for preparing sucralose-<NUM>-ethyl ester, neutralizing an obtained acid material with alkali, adding a non-polar or a low-polar solvent, and leaving the mixture to stand after stirring such that the sucralose-<NUM>-ethyl ester forms a solid; subjecting a resulting system to solid-liquid separation to obtain a crude product of sucralose-<NUM>-ethyl ester solid; and optionally, recycling a liquid part after rectification separation, and recrystallizing the crude product of sucralose-<NUM>-ethyl ester solid.

Chinese patent <CIT> discloses a method for preparing sucralose-<NUM>-ethyl ester, which comprises: (<NUM>) adding sucrose-<NUM>-ethyl ester into a solvent containing N-formyl groups, cooling to below <NUM>, and adding thionyl chloride dropwise to react with N-formyl groups in the solvent; and heating a resulting mixture up to <NUM>-<NUM> for <NUM>-<NUM> hours, and then heating up to <NUM>-<NUM> for <NUM>-<NUM> hours, finally heating up to <NUM>-<NUM> for <NUM>-<NUM> hours, the whole heating process and reaction are protected by chlorine gas; (<NUM>) cooling a resulting system to room temperature, adjusting the system to neutral by alkali, extracting the system with ethyl acetate, and concentrating a resulting extract to obtain a sucralose-<NUM>-ethyl ester solution; and adding a small amount of ether solvent or water to the sucralose-<NUM>-ethyl ester solution to obtain sucralose-<NUM>-ethyl ester crystals.

Chinese patent <CIT> discloses a method for refining sucralose-<NUM>-ethyl ester, which comprises: refining a sucralose-<NUM>-ethyl ester crude product obtained by concentration for the first time by using an alcohol-ether mixed solvent to remove most impurities; and refining the crude product for the second time by using an ester-alkane mixed solvent to remove trace impurities so as to obtain a high-purity sucralose-<NUM>-ethyl ester fine product.

Industrially, sucralose-<NUM>-acetate is obtained through chlorination of sucrose-<NUM>-acetate, and by-products produced during the chlorination mainly include monochlorosucrose-<NUM>-acetate, dichlorosucrose-<NUM>-acetate, tetrachlorosucrose-<NUM>-acetate, or the like, where monochlorinated and dichlorinated by-products are common. Ethyl acetate, which is commonly used in industry, has excellent polarity and includes an ester group. According to the principle of similar compatibility, ethyl acetate has a high solubility for the four products. However, the use of a single solvent inevitably fails to effectively separate a variety of by-products; thus, it is easy to cause problems in the current process such as poor crystallization efficiency of ethyl acetate, large number of crystallization times, and large organic solvent consumption.

In view of the above problems, the present disclosure provides a method for purifying sucralose-<NUM>-acetate in order to overcome the above problems.

To achieve the above object, the present disclosure provides the following technical solutions:
A method for purifying sucralose-<NUM>-acetate, including:.

In some embodiments, the predetermined temperature of the saturated solution of crude sucralose-<NUM>-acetate in ethyl acetate is in a range of <NUM> to <NUM>.

In some embodiments, the low-polarity solvent is one or more selected from the group consisting of n-pentane, cyclopentane, n-hexane, cyclohexane, n-heptane, and cycloheptane.

In some embodiments, in the gradient crystallization, the saturated solution is subjected to the cooling crystallization for three or more times.

In some embodiments, in the purification, the crude sucralose-<NUM>-acetate is dissolved at a temperature of <NUM> to <NUM> for recrystallization; the mixed solution of ethyl acetate and the low-polarity solvent is stirred at a rate of <NUM> r/min to <NUM> r/min; a volume ratio of ethyl acetate to the low-polarity solvent is in a range of <NUM>:(<NUM>-<NUM>); and the recrystallization is conducted at a temperature of -<NUM> to <NUM> for <NUM> hours to <NUM> hours.

In some embodiments, the purification further includes: drying a sucralose-<NUM>-acetate solid obtained by filtration with a dryer to obtain the fine sucralose-<NUM>-acetate of high purity.

In some embodiments, the method further includes:
recovery: collecting a first mother liquor obtained by filtration after the third cooling crystallization in the gradient crystallization and a second mother liquor obtained by filtration after the recrystallization for purification, and recovering ethyl acetate and the low-polarity solvent from the first mother liquor and the second mother liquor.

In some embodiments, in the recovery, under the condition that the low-polarity solvent includes one selected from the group consisting of n-pentane, cyclopentane, and n-hexane, the low-polarity solvent is first recovered from the first mother liquor and the second mother liquor, and then ethyl acetate is recovered; and under the condition that the low-polarity solvent includes one selected from the group consisting of cyclohexane, n-heptane, and cycloheptane, ethyl acetate is first recovered from the first mother liquor and the second mother liquor, and then the low-polarity solvent is recovered.

In summary, the present disclosure has the following beneficial effects:
In the method of the present disclosure, ethyl acetate is used as an initial solvent for cooling crystallization of sucralose-<NUM>-acetate, and a low-polarity solvent is added step by step with the decrease of temperature to make the polarity of the mixed solvent show a trend of gradient reduction during the crystallization, such that impurities could be effectively separated due to polarity changes, which enables high single-pass crystallization yield and efficiency of sucralose-<NUM>-acetate, ensures the purity of a crystallization product, and reduces the number of crystallization times and the consumption of the organic solvent, thereby leading to high product yield, purity, and quality.

where V-<NUM> refers to a low-polarity solvent storage tank; V-<NUM> refers to an ethyl acetate storage tank; E-<NUM> refers to a first crystallization reactor; E-<NUM> refers to a second crystallization reactor; E-<NUM> refers to a third crystallization reactor; E-<NUM> refers to a fourth crystallization reactor; E-<NUM> and E-<NUM> each refers to a solvent recovery tower; H-<NUM> refers to a first solid-liquid separator; H-<NUM> refers to a second solid-liquid separator; H-<NUM> refers to a third solid-liquid separator; H-<NUM> refers to a fourth solid-liquid separator; and H-<NUM> refers to a dryer.

To make the object, technical solutions, and advantages of the present disclosure clear, embodiments of the present disclosure will be further described in detail with reference to the accompanying drawings. Although exemplary embodiments of the present disclosure are shown in the accompanying drawings, it should be understood that the present disclosure may be implemented in various forms and should not be limited to the embodiments set forth herein. Instead, these embodiments are provided to make the present disclosure thoroughly understood and make a protection scope of the present disclosure clear to those skilled in the art.

The by-products produced during the preparation of sucralose-<NUM>-acetate are mostly monochlorinated and dichlorinated by-products. Moreover, each chlorinated product has a specified polarity, and the polarity gradually increases with the increase of the number of chlorine groups, that is, the four products rank as follows in terms of polarity: tetrachlorosucrose-<NUM>-acetate > sucralose-<NUM>-acetate > dichlorosucrose-<NUM>-acetate > monochlorosucrose-<NUM>-acetate. Although ethyl acetate used in industry has excellent polarity and exhibits high solubility for the four chlorinated products, the recrystallization for purification using a single solvent inevitably fails to effectively separate a variety of by-products.

The technical concept of the present disclosure is as follows: An ethyl acetate saturated solution is used for cooling crystallization of sucralose-<NUM>-acetate, and a low-polarity solvent is added step by step with the decrease in temperature to reduce the polarity of the solution in stages, such that impurities could be effectively separated and a crystalline purity of sucralose-<NUM>-acetate could be improved at each stage, thereby reducing the number of crystallization times and the organic solvent consumption, and making it possible to ensure a high single-pass crystallization yield and the purity of a crystallization product. The method of the present disclosure has strong operability and makes it possible to obtain product with high yield, high purity, and good quality.

<FIG> is a flowchart showing a method for purifying sucralose-<NUM>-acetate according to an embodiment of the present disclosure. As shown in <FIG>, the method includes:.

Since the purity of the crude sucralose-<NUM>-acetate is improved at each stage of the gradient crystallization, under the condition of the same number of crystallization times, the purity of the final sucralose-<NUM>-acetate product in the embodiment is significantly improved.

In an embodiment of the present disclosure, the temperature of the saturated solution of crude sucralose-<NUM>-acetate in ethyl acetate is in a range of <NUM> to <NUM>. Ethyl acetate has excellent polarity and includes ester groups. According to the principle of similar compatibility, ethyl acetate exhibits high solubility for the four chlorinated products, which could effectively ensure the product yield. In the present disclosure, ethyl acetate with excellent polarity is first used alone, and with the progress of cooling crystallization, a low-polarity solvent is gradually added to reduce the overall polarity of the solvent in the solution system, such that monochlorinated product and dichlorinated product of low polarity are effectively separated due to the gradient changes of the polarity of the solvent, which promotes the precipitation of the target product sucralose-<NUM>-acetate and realizes the efficient and high-purity purification of sucralose-<NUM>-acetate.

In an embodiment of the present disclosure, the low-polarity solvent is one or more selected from the group consisting of n-pentane, cyclopentane, n-hexane, cyclohexane, n-heptane, and cycloheptane. Of course, the low-polarity solvent available in the present disclosure is not limited to the above solvents, and any low-polarity solvent that can be mixed with ethyl acetate to produce a mixed solvent with reduced polarity, does not react with the target product in the solution, and is easy to separate may be used in the present disclosure.

In an embodiment of the present disclosure, in the gradient crystallization, the saturated solution is subjected to the cooling crystallization for three or more times.

In some preferred embodiments of the present disclosure, an excellent purification effect could be achieved by gradually reducing the polarity of the solvent and conducting cooling crystallization for <NUM> times. Of course, increased cooling crystallization times could bring an improved purification effect, but would also increase the cost. Therefore, the actual number of cooling crystallization times could be determined according to the production needs.

In the present disclosure, in the gradient crystallization, the saturated solution of crude sucralose-<NUM>-acetate in ethyl acetate is subjected to the cooling crystallization for three times, where a first cooling crystallization is conducted at a temperature of <NUM> to <NUM>, a second cooling crystallization is conducted at a temperature of <NUM> to <NUM>, and a third cooling crystallization is conducted at a temperature of -<NUM> to <NUM>.

In some embodiments, in the gradient crystallization, the low-polarity solvent is added dropwise for <NUM> minutes to <NUM> minutes in an amount of <NUM>% to <NUM>% of a volume of the saturated solution during each cooling crystallization process.

In some embodiments, the cooling crystallization is conducted for three times, where a first cooling crystallization is conducted for <NUM> hours to <NUM> hour, a second cooling crystallization is conducted for <NUM> hours to <NUM> hours, and a third cooling crystallization is conducted for <NUM> hours to <NUM> hours; and the resulting solution is stirred at a rate of <NUM> r/min to <NUM> r/min during each cooling crystallization process.

In an embodiment of the present disclosure, in the purification, the crude sucralose-<NUM>-acetate is dissolved at a temperature of <NUM> to <NUM> for recrystallization; the mixed solution of ethyl acetate and the low-polarity solvent is stirred at a rate of <NUM> r/min to <NUM> r/min; a volume ratio of ethyl acetate to the low-polarity solvent is in a range of <NUM> :(<NUM>-<NUM>); and the recrystallization is conducted at a temperature of -<NUM> to <NUM> for <NUM> hours to <NUM> hours. The above method is not much different from the existing method for purifying sucralose-<NUM>-acetate by ethyl acetate recrystallization, and is mainly intended to further purify and unify the purities of sucralose-<NUM>-acetate products at different concentrations produced at different stages.

In an embodiment of the present disclosure, the purification further includes: drying a sucralose-<NUM>-acetate solid obtained by filtration with a dryer to obtain the fine sucralose-<NUM>-acetate of high purity.

<FIG> is a flowchart showing the method for purifying sucralose-<NUM>-acetate according to another embodiment of the present disclosure. In the embodiment of <FIG>, the method further includes:
S140: Recovery: A first mother liquor obtained by filtration after the third cooling crystallization in the gradient crystallization and a second mother liquor obtained by filtration after the recrystallization for purification are collected, and ethyl acetate and the low-polarity solvent are recovered from the first mother liquor and the second mother liquor. Thus, in the method of the present disclosure, ethyl acetate and the low-polarity solvent could be recovered and recycled, which makes it possible to reduce the process cost.

In an embodiment of the present disclosure, in the recovery, under the condition that the low-polarity solvent includes one selected from the group consisting of n-pentane, cyclopentane, and n-hexane, the low-polarity solvent is first recovered from the first mother liquor and the second liquor, and then ethyl acetate is recovered; and under the condition that the low-polarity solvent includes one selected from the group consisting of cyclohexane, n-heptane, and cycloheptane, ethyl acetate is first recovered from the first mother liquor and the second mother liquor, and then the low-polarity solvent is recovered. When other low-polarity solvents are used, a recovery order may be adjusted according to properties such as the boiling points of the low-polarity solvents and ethyl acetate.

<FIG> is a process flowchart showing the method for purifying sucralose-<NUM>-acetate according to an embodiment of the present disclosure. In the process shown in <FIG>, the purification of crude sucralose-<NUM>-acetate is achieved by conducting cooling crystallization for three times during the gradient crystallization. The following examples are illustrated with reference to the process flowchart shown in <FIG>.

<NUM><NUM> of a <NUM> saturated solution of crude sucralose-<NUM>-acetate in ethyl acetate (purity: greater than <NUM>%, commercially available) (the saturated solution was prepared by dissolving crude sucralose-<NUM>-acetate obtained from a sucralose production process in ethyl acetate, and the purity was tested by high performance liquid chromatography (HPLC)) was added to a first crystallization reactor E-<NUM>, stirred at a rate of <NUM> r/min, and cooled to <NUM>. <NUM> of n-pentane (purity: greater than <NUM>%, commercially available) was added dropwise for <NUM> minutes, and a resulting system was further stirred for <NUM> hours to allow a crystallization. After the crystallization was completed, a resulting mixture was subjected to a first solid-liquid separation (SLS) in a first solid-liquid separator H-<NUM>. A resulting mother liquor was transported to a second crystallization reactor E-<NUM>, cooled to <NUM>, and stirred at a rate of <NUM> r/min. Then <NUM> of n-pentane was added dropwise for <NUM> minutes, and a resulting system was further stirred for <NUM> hours to allow a continued crystallization. After the crystallization was completed, a resulting mixture was subjected to a second SLS in a second solid-liquid separator H-<NUM>. A resulting mother liquor was transported to a third crystallization reactor E-<NUM>, cooled to <NUM>, and stirred at a rate of <NUM> r/min. Then <NUM> of n-pentane was added dropwise for <NUM> minutes, and a resulting system was further stirred for <NUM> hours to allow a further crystallization. After the crystallization was completed, a resulting mixture was subjected to a third SLS in a third solid-liquid separator H-<NUM>, and a resulting mother liquor was transported to recovery towers E-<NUM> and E-<NUM> for solvent recovery. The gradient crystallization was completed.

<NUM><NUM> of a mixed solvent of ethyl acetate and n-pentane in a volume ratio of <NUM>:<NUM> was added to a fourth crystallization reactor E-<NUM>, and crude sucralose-<NUM>-acetate products obtained from the first solid-liquid separator H-<NUM>, the second solid-liquid separator H-<NUM>, and the third solid-liquid separator H-<NUM> were added to the fourth crystallization reactor E-<NUM>. A resulting mixture was heated and stirred for complete dissolution, then cooled to -<NUM>, and subjected to a crystallization for <NUM> hour. A resulting sucralose-<NUM>-acetate solid was dried by a dryer H-<NUM> to obtain a fine sucralose-<NUM>-acetate of high purity, and a resulting mother liquor was combined with the mother liquor obtained from the third solid-liquid separator H-<NUM> and transported to recovery towers E-<NUM> and E-<NUM> for recovering ethyl acetate and the low-polarity solvent. In example <NUM>, the low-polarity solvent was n-pentane with a lower boiling point than that of ethyl acetate. The solvent recovery tower E-<NUM> was a low-polarity solvent recovery tower, which was configured to recover n-pentane and was connected to a low-polarity solvent storage tank V-<NUM>. The solvent recovery tower E-<NUM> was an ethyl acetate recovery tower, which was connected to an ethyl acetate storage tank V-<NUM>. In other examples of the present disclosure, a solvent recovery order of the solvent recovery towers E-<NUM> and E-<NUM> was determined according to the boiling points of the low-polarity solvent and ethyl acetate, and the principle was the same, which would not be repeated. A purity of sucralose-<NUM>-acetate at each stage and a total yield of sucralose-<NUM>-acetate were shown in Table <NUM>.

<NUM><NUM> of a <NUM> saturated solution of crude sucralose-<NUM>-acetate in ethyl acetate (purity: greater than <NUM>%, commercially available) (the saturated solution was prepared by dissolving crude sucralose-<NUM>-acetate obtained from a sucralose production process in ethyl acetate, and the purity was tested by HPLC) was added to a first crystallization reactor E-<NUM>, stirred at a rate of <NUM> r/min, and cooled to <NUM>. <NUM> of cyclopentane was added dropwise for <NUM> minutes, and a resulting system was further stirred for <NUM> minutes to allow a crystallization. After the crystallization was completed, a resulting mixture was subjected to a first SLS in a first solid-liquid separator H-<NUM>. A resulting mother liquor was transported to a second crystallization reactor E-<NUM>, cooled to <NUM>, and stirred at a rate of <NUM> r/min. Then <NUM> of cyclopentane was added dropwise for <NUM> minutes, and a resulting system was further stirred for <NUM> hour to allow a continued crystallization. After the crystallization was completed, a resulting mixture was subjected to a second SLS in a second solid-liquid separator H-<NUM>. A resulting mother liquor was transported to a third crystallization reactor E-<NUM>, cooled to -<NUM>, and stirred at a rate of <NUM> r/min. Then <NUM> of n-pentane (purity: greater than <NUM>%, commercially available) was added dropwise for <NUM> minutes, and a resulting system was further stirred for <NUM> hour to allow a further crystallization. After the crystallization was completed, a resulting mixture was subjected to a third SLS in a third solid-liquid separator H-<NUM>, and a resulting mother liquor was transported to solvent recovery towers for solvent recovery.

<NUM><NUM> of a mixed solvent of ethyl acetate and n-pentane in a volume ratio of <NUM>:<NUM> was added to a fourth crystallization reactor E-<NUM>, and crude sucralose-<NUM>-acetate products obtained from the first solid-liquid separator H-<NUM>, the second solid-liquid separator H-<NUM>, and the third solid-liquid separator H-<NUM> were added to the fourth crystallization reactor E-<NUM>. A resulting mixture was heated and stirred for complete dissolution, then cooled to -<NUM>, and subjected to a crystallization for <NUM> hours. A resulting sucralose-<NUM>-acetate solid was dried by a dryer H-<NUM> to obtain a fine sucralose-<NUM>-acetate of high purity, and a resulting mother liquor was combined with the mother liquor obtained from the third solid-liquid separator H-<NUM> and transported to solvent recovery towers for recovering ethyl acetate and the low-polarity solvent. A purity of sucralose-<NUM>-acetate at each stage and a total yield of sucralose-<NUM>-acetate were shown in Table <NUM>.

<NUM><NUM> of a <NUM> saturated solution of crude sucralose-<NUM>-acetate in ethyl acetate (purity: greater than <NUM>%, commercially available) (the saturated solution was prepared by dissolving crude sucralose-<NUM>-acetate obtained from a sucralose production process in ethyl acetate, and the purity was tested by HPLC) was added to a first crystallization reactor E-<NUM>, stirred at a rate of <NUM> r/min, and cooled to <NUM>. <NUM> of n-hexane (purity: greater than <NUM>%, commercially available) was added dropwise for <NUM> minutes, and a resulting system was further stirred for <NUM> minutes to allow a crystallization. After the crystallization was completed, a resulting mixture was subjected to a first SLS in a first solid-liquid separator H-<NUM>. A resulting mother liquor was transported to a second crystallization reactor E-<NUM>, cooled to <NUM>, and stirred at a rate of <NUM> r/min. Then <NUM> of n-pentane was added dropwise for <NUM> minutes, and a resulting system was further stirred for <NUM> hour to allow a continued crystallization. After the crystallization was completed, a resulting mixture was subjected to a second SLS in a second solid-liquid separator H-<NUM>. A resulting mother liquor was transported to a third crystallization reactor E-<NUM>, cooled to <NUM>, and stirred at a rate of <NUM> r/min. Then <NUM> of n-pentane was added dropwise for <NUM> minutes, and a resulting system was further stirred for <NUM> hours to allow a further crystallization. After the crystallization was completed, a resulting mixture was subjected to a third SLS in a third solid-liquid separator H-<NUM>, and a resulting mother liquor was transported to solvent recovery towers for solvent recovery.

<NUM><NUM> of a mixed solvent of ethyl acetate and n-pentane in a volume ratio of <NUM>:<NUM> was added to a fourth crystallization reactor, and crude sucralose-<NUM>-acetate products obtained from the first solid-liquid separator H-<NUM>, the second solid-liquid separator H-<NUM>, and the third solid-liquid separator H-<NUM> were added to the fourth crystallization reactor. A resulting mixture was heated and stirred for complete dissolution, then cooled to -<NUM>, and subjected to a crystallization for <NUM> hour. A resulting sucralose-<NUM>-acetate solid was dried by a dryer H-<NUM> to obtain a fine sucralose-<NUM>-acetate of high purity, and a resulting mother liquor was combined with the mother liquor obtained from the third solid-liquid separator H-<NUM> and transported to solvent recovery towers for recovering ethyl acetate and the low-polarity solvent. A purity of sucralose-<NUM>-acetate at each stage and a total yield of sucralose-<NUM>-acetate were shown in Table <NUM>.

<NUM><NUM> of a <NUM> saturated solution of crude sucralose-<NUM>-acetate in ethyl acetate (purity: greater than <NUM>%, commercially available) (the saturated solution was prepared by dissolving crude sucralose-<NUM>-acetate obtained from a sucralose production process in ethyl acetate, and the purity was tested by HPLC) was added to a first crystallization reactor E-<NUM>, stirred at a rate of <NUM> r/min, and cooled to <NUM>. <NUM> of cyclohexane was added dropwise for <NUM> minutes, and a resulting system was further stirred for <NUM> minutes to allow a crystallization. After the crystallization was completed, a resulting mixture was subjected to a first SLS in a first solid-liquid separator H-<NUM>. A resulting mother liquor was transported to a second crystallization reactor E-<NUM>, cooled to <NUM>, and stirred at a rate of <NUM> r/min. Then <NUM> of n-pentane (purity: greater than <NUM>%, commercially available) was added dropwise for <NUM> minutes, and a resulting system was further stirred for <NUM> hour to allow a continued crystallization. After the crystallization was completed, a resulting mixture was subjected to a second SLS in a second solid-liquid separator H-<NUM>. A resulting mother liquor was transported to a third crystallization reactor E-<NUM>, cooled to <NUM>, and stirred at a rate of <NUM> r/min. Then <NUM> of n-pentane was added dropwise for <NUM> minutes, and a resulting system was further stirred for <NUM> hours to allow a further crystallization. After the crystallization was completed, a resulting mixture was subjected to a third SLS in a third solid-liquid separator H-<NUM>, and a resulting mother liquor was transported to solvent recovery towers for solvent recovery.

<NUM><NUM> of a mixed solvent of ethyl acetate and n-pentane in a volume ratio of <NUM>:<NUM> was added to a fourth crystallization reactor, and crude sucralose-<NUM>-acetate products obtained from the first solid-liquid separator H-<NUM>, the second solid-liquid separator H-<NUM>, and the third solid-liquid separator H-<NUM> were added to the fourth crystallization reactor. A resulting mixture was heated and stirred for complete dissolution, then cooled to -<NUM>, and subjected to a crystallization for <NUM> hours. A resulting sucralose-<NUM>-acetate solid was dried by a dryer H-<NUM> to obtain a fine sucralose-<NUM>-acetate of high purity, and a resulting mother liquor was combined with the mother liquor obtained from the third solid-liquid separator H-<NUM> and transported to solvent recovery towers for recovering ethyl acetate and the low-polarity solvent. A purity of sucralose-<NUM>-acetate at each stage and a total yield of sucralose-<NUM>-acetate were shown in Table <NUM>.

<NUM><NUM> of a <NUM> saturated solution of crude sucralose-<NUM>-acetate in ethyl acetate (purity: greater than <NUM>%, commercially available) (the saturated solution was prepared by dissolving crude sucralose-<NUM>-acetate obtained from a sucralose production process in ethyl acetate, and the purity was tested by HPLC) was added to a first crystallization reactor E-<NUM>, stirred at a rate of <NUM> r/min, and cooled to <NUM>. <NUM> of n-heptane (purity: greater than <NUM>%, commercially available) was added dropwise for <NUM> minutes, and a resulting system was further stirred for <NUM> hours to allow a crystallization. After the crystallization was completed, a resulting mixture was subjected to a first SLS in a first solid-liquid separator H-<NUM>. A resulting mother liquor was transported to a second crystallization reactor E-<NUM>, cooled to <NUM>, and stirred at a rate of <NUM> r/min. Then <NUM> of n-pentane was added dropwise for <NUM> minutes, and a resulting system was further stirred for <NUM> hours to allow a continued crystallization. After the crystallization was completed, a resulting mixture was subjected to a second SLS in a second solid-liquid separator H-<NUM>. A resulting mother liquor was transported to a third crystallization reactor E-<NUM>, cooled to -<NUM>, and stirred at a rate of <NUM> r/min. Then <NUM> of n-pentane was added dropwise for <NUM> minutes, and a resulting system was further stirred for <NUM> hours to allow a further crystallization. After the crystallization was completed, a resulting mixture was subjected to a third SLS in a third solid-liquid separator H-<NUM>, and a resulting mother liquor was transported to solvent recovery towers for solvent recovery.

<NUM><NUM> of a <NUM> saturated solution of crude sucralose-<NUM>-acetate in ethyl acetate (purity: greater than <NUM>%, commercially available) (the saturated solution was prepared by dissolving crude sucralose-<NUM>-acetate obtained from a sucralose production process in ethyl acetate, and the purity was tested by HPLC) was added to a first crystallization reactor E-<NUM>, stirred at a rate of <NUM> r/min, and cooled to <NUM>. <NUM> of cycloheptane (purity: greater than <NUM>%, commercially available) was added dropwise for <NUM> minutes, and a resulting system was further stirred for <NUM> hour to allow a crystallization. After the crystallization was completed, a resulting mixture was subjected to a first SLS in a first solid-liquid separator H-<NUM>. A resulting mother liquor was transported to a second crystallization reactor E-<NUM>, cooled to <NUM>, and stirred at a rate of <NUM> r/min. Then <NUM> of n-pentane was added dropwise for <NUM> minutes, and a resulting system was further stirred for <NUM> hours to allow a continued crystallization. After the crystallization was completed, a resulting mixture was subjected to a second SLS in a second solid-liquid separator H-<NUM>. A resulting mother liquor was transported to a third crystallization reactor E-<NUM>, cooled to -<NUM>, and stirred at a rate of <NUM> r/min. Then <NUM> of n-pentane was added dropwise for <NUM> minutes, and a resulting system was further stirred for <NUM> hours to allow a further crystallization. After the crystallization was completed, a resulting mixture was subjected to a third SLS in a third solid-liquid separator H-<NUM>, and a resulting mother liquor was transported to solvent recovery towers for solvent recovery.

<NUM><NUM> of a <NUM> saturated solution of crude sucralose-<NUM>-acetate in ethyl acetate (purity: greater than <NUM>%, commercially available) (the saturated solution was prepared by dissolving crude sucralose-<NUM>-acetate obtained from a sucralose production process in ethyl acetate, and the purity was tested by HPLC) was added to a first crystallization reactor E-<NUM>, stirred at a rate of <NUM> r/min, and cooled to <NUM>. <NUM> of cyclohexane (purity: greater than <NUM>%, commercially available) was added dropwise for <NUM> minutes, and a resulting system was further stirred for <NUM> hour to allow a crystallization. After the crystallization was completed, a resulting mixture was subjected to a first SLS in a first solid-liquid separator H-<NUM>. A resulting mother liquor was transported to a second crystallization reactor E-<NUM>, cooled to <NUM>, and stirred at a rate of <NUM> r/min. Then <NUM> of n-pentane was added dropwise for <NUM> minutes, and a resulting system was further stirred for <NUM> hours to allow a continued crystallization. After the crystallization was completed, a resulting mixture was subjected to a second SLS in a second solid-liquid separator H-<NUM>. A resulting mother liquor was transported to a third crystallization reactor E-<NUM>, cooled to -<NUM>, and stirred at a rate of <NUM> r/min. Then <NUM> of n-pentane was added dropwise for <NUM> minutes, and a resulting system was further stirred for <NUM> hours to allow a further crystallization. After the crystallization was completed, a resulting mixture was subjected to a third SLS in a third solid-liquid separator H-<NUM>, and a resulting mother liquor was transported to solvent recovery towers for solvent recovery.

<NUM><NUM> of a <NUM> saturated solution of crude sucralose-<NUM>-acetate in ethyl acetate (purity: greater than <NUM>%, commercially available) (the saturated solution was prepared by dissolving crude sucralose-<NUM>-acetate obtained from a sucralose production process in ethyl acetate, and the purity was tested by HPLC) was added to a first crystallization reactor E-<NUM>, stirred at a rate of <NUM> r/min, and cooled to <NUM>. <NUM> of n-heptane (purity: greater than <NUM>%, commercially available) was added dropwise for <NUM> minutes, and a resulting system was further stirred for <NUM> hour to allow a crystallization. After the crystallization was completed, a resulting mixture was subjected to a first SLS in a first solid-liquid separator H-<NUM>. A resulting mother liquor was transported to a second crystallization reactor E-<NUM>, cooled to <NUM>, and stirred at a rate of <NUM> r/min. Then <NUM> of n-pentane was added dropwise for <NUM> minutes, and a resulting system was further stirred for <NUM> hours to allow a continued crystallization. After the crystallization was completed, a resulting mixture was subjected to a second SLS in a second solid-liquid separator H-<NUM>. A resulting mother liquor was transported to a third crystallization reactor E-<NUM>, cooled to -<NUM>, and stirred at a rate of <NUM> r/min. Then <NUM> of n-pentane was added dropwise for <NUM> minutes, and a resulting system was further stirred for <NUM> hours to allow a further crystallization. After the crystallization was completed, a resulting mixture was subjected to a third SLS in a third solid-liquid separator H-<NUM>, and a resulting mother liquor was transported to solvent recovery towers for solvent recovery.

<NUM><NUM> of a <NUM> saturated solution of crude sucralose-<NUM>-acetate in ethyl acetate (purity: greater than <NUM>%, commercially available) (the saturated solution was prepared by dissolving crude sucralose-<NUM>-acetate obtained from a sucralose production process in ethyl acetate, and the purity was tested by HPLC) was added to a first crystallization reactor E-<NUM>, stirred at a rate of <NUM> r/min, and cooled to <NUM>. <NUM> of cyclopentane (purity: greater than <NUM>%, commercially available) was added dropwise for <NUM> minutes, and a resulting system was further stirred for <NUM> minutes to allow a crystallization. After the crystallization was completed, a resulting mixture was subjected to a first SLS in a first solid-liquid separator H-<NUM>. A resulting mother liquor was transported to a second crystallization reactor E-<NUM>, cooled to <NUM>, and stirred at a rate of <NUM> r/min. Then <NUM> of n-pentane was added dropwise for <NUM> minutes, and a resulting system was further stirred for <NUM> hours to allow a continued crystallization. After the crystallization was completed, a resulting mixture was subjected to a second SLS in a second solid-liquid separator H-<NUM>. A resulting mother liquor was transported to a third crystallization reactor E-<NUM>, cooled to -<NUM>, and stirred at a rate of <NUM> r/min. Then <NUM> of n-pentane was added dropwise for <NUM> minutes, and a resulting system was further stirred for <NUM> hours to allow a further crystallization. After the crystallization was completed, a resulting mixture was subjected to a third SLS in a third solid-liquid separator H-<NUM>, and a resulting mother liquor was transported to solvent recovery towers for solvent recovery.

In summary, in the method for purifying sucralose-<NUM>-acetate of the present disclosure, ethyl acetate is used as an initial solvent for cooling crystallization of sucralose-<NUM>-acetate, and a low-polarity solvent is added step by step with the decrease of temperature to make the polarity of the mixed solvent show a trend of gradient reduction during the crystallization, such that impurities could be effectively separated at different gradient stages, which enables high single-pass crystallization yield and efficiency, ensures the purity of a crystallization product, and reduces the number of crystallization times and the consumption of the organic solvent, thereby leading to high product yield, purity, and quality.

Claim 1:
A method for purifying sucralose-<NUM>-acetate, comprising:
preparation: providing a saturated solution of crude sucralose-<NUM>-acetate in ethyl acetate which is heated to a predetermined temperature;
gradient crystallization: subjecting the saturated solution to multiple cooling crystallization and filtration, and collecting crude sucralose-<NUM>-acetate obtained after the multiple cooling crystallization and filtration, wherein during each cooling crystallization process, a low-polarity solvent is added dropwise to the saturated solution to reduce a polarity of the saturated solution during crystallization step by step; and
purification: subjecting the collected crude sucralose-<NUM>-acetate to recrystallization for purification by using a mixed solution of ethyl acetate and the low-polarity solvent to obtain fine sucralose-<NUM>-acetate of high purity;
wherein in the gradient crystallization, the saturated solution is subjected to the cooling crystallization for three times, wherein a first cooling crystallization is conducted at a temperature of <NUM> to <NUM>, a second cooling crystallization is conducted at a temperature of <NUM> to <NUM>, and a third cooling crystallization is conducted at a temperature of -<NUM> to <NUM>.