AT17930U1 - Process for the manufacture of dexibuprofen - Google Patents

Abstract

The present invention discloses a process for preparing dexibuprofen comprising: (1) placing toluene in a reaction vessel, adding ibuprofen and n-octyl-d-glucamine, heating to 76 to 80°C, conducting the reaction at the maintained temperature above 0.5 hours, transferring the material to an amine salt crystallizing kettle, cooling to crystallize after adding purified water, centrifuging and separating, washing and drying after lowering the temperature to 18 to 22°C to obtain dexibuprofen-n-octyl -d-glucamine salt, the feeding ratio of ibuprofen: n-octyl-d-glucamine: toluene: purified water being 1: 0.65~0.75:7.5~8:0.01~0.02 amounts; (2) performing a hydrolysis reaction to precipitate n-octyl-d-glucamine; (3) Conducting an acidification reaction to precipitate dexibuprofen. The applicant finally found that the ratio of the volume of purified water to the weight of ibuprofen in the production of amine salt is 0.01~0.02L:1kg, so the molar yield of dexibuprofen is finally high and the melting point of Dextro amine salt can meet an acceptable standard of 135~140°C.

Description

Description

PROCESS FOR THE MANUFACTURE OF DEXIBUPROFEN

TECHNICAL PART

The invention relates to the technical field of organic synthesis, in particular to a process for the production of dexibuprofen.

STATE OF THE ART

The process of separating racemates into pure levo or dextro isomers is called racemic resolution, and chemical resolution is one of the common resolution methods. The chemical method uses a resolving agent to separate the racemate, and an optically active organic acid or an alkali is often used as the resolving agent. Dexibuprofen is the right-handed form of ibuprofen. Research has found that the pharmacological activity of ibuprofen mainly comes from the dextromer, which has a higher curative effect compared to ibuprofen racemate at the same dose and can achieve the therapeutic effect at a lower dose. Dexibuprofen and ibuprofen have the same effects and uses, but the effects of dexibuprofen at doses of 150 mg and 300 mg are equivalent to the effects of ibuprofen at 200 mg and 400 mg. Dexibuprofen is better than ibuprofen in terms of safety and pharmacokinetic properties. Therefore, it is necessary to separate dexibuprofen from ibuprofen.

Comparative document: the application number is "CN02138434.7" and the title is "Preparation of dextroibuprofen". It discloses a process for the production of dexibuprofen((+)I) by resolution of racemic ibuprofen((+)I) by a host-guest crystallization reaction kinetics control process. With N-octyl-d-glucamine or a-phenhexylamine, cinchonidine, L-lysine and meglumine ((+)II) as the host, racemic ibuprofen ((+)I) as the guest, and ethanol (III) as the solvent, the salt formation reaction proceeds carried out at normal pressure and a temperature of 10-85°C. The salt ((A1-(AII)) formed from dextribuprofen (+)I) and the host cleaving reagent ((+)II) precipitates as a crystal, while that of levibuprofen ((-)I) and the cleaving reagent (AI ) formed salt ((-)I-(+)II) dissolves in the solvent.To separate ((+)1-(+)I)-salt, a pH=10 is first adjusted in water with an NaCOH solution and solid (+)II is filtered off. A pH value is then adjusted to 1-2 with hydrochloric acid and (+)l is precipitated. The salt (-)l-(+)Il dissolved in the solvent is formed by racemization ((+)l) recovered and split again.In each step, the ratio of materials and the temperature is strictly controlled to monitor the dissolution and quality of (+)!.The primary dissolution is 27-33%, the mass content of (+)I is = 99.5% and the specific rotation [a]D is 56-59° Although the resolution in the comparative document is high, the dextroamine salt produced according to the reaction conditions of the process has a very low melting point and the content of levo isomer in that by hydrolysis and acidification The dexibuprofen obtained is significantly above the acceptable standard. How to improve this method so that the molar yield of dexibuprofen is high and the melting point of the dextroamine salt meets the acceptable standard has become a technical problem to be urgently solved.

CONTENT OF THE INVENTION

The object of the present invention is to overcome the deficiencies of the prior art and to provide a process for the production of dexibuprofen such that the molar yield of dexibuprofen is high and the melting point of dextroamine salt is within the acceptable standard.

The present invention is realized in this way: The object of the present invention is to provide a method for the production of

to provide dexibuprofen, the method described comprising the following steps: Step 1: Salt formation reaction to produce Dexibuprofen-N-octyl-d-glucamine salt:

After toluene has been placed in a reaction vessel, ibuprofen and N-octyl-dglucamine are added and the mixture is heated to 76-80° C. with stirring. At the kept temperature, the reaction is carried out for 0.5 hour. The material is transferred to an amine salt crystallization kettle. Purified water is added and cooled to crystallize. When the temperature drops to 18-22°C, centrifugation, washing and drying are performed to obtain Dexibuprofen-N-octyl-d-glucamine salt. The feeding ratio of ibuprofen: N-octyl-d-glucamine: toluene: purified water is 1: 0.65-0.75:7.5-8:0.01-0.02, where the unit of ibuprofen and N- Octyl-d-glucamine in this ratio is kg and the unit of toluene and purified water is L;

Step 2: hydrolysis reaction to precipitate N-octyl-d-glucamine to fill in:

The alkaline salt solution is added to the dexibuprofen-N-octyl-d-glucamine salt obtained in Step 1 to carry out hydrolysis reaction to precipitate and remove N-octyl-d-glucamine;

Step 3: Acidification Reaction to Precipitate Dexibuprofen:

After the pH of the material obtained after removal of N-octyl-d-glucamine in step 2 is adjusted to 1 to 2 with hydrochloric acid, a wet crude product of dexibuprofen is obtained by cooling and centrifugation. Then a finished product of dexibuprofen is obtained by refining.

Compared with the prior art, the present invention has the following advantages and effects: a process for the production of dexibuprofen, wherein the applicant adopts the cleavage process for dexibuprofen, using toluene as a solvent and N-octyld-glucamine as a cleavage reagent, ibuprofen is cleaved to obtain amine salt which is then hydrolyzed and acidified to obtain dexibuprofen. In the case of extremely low water content of the three raw and excipients N-octyl-d-glucamine, ibuprofen and toluene in the production of dexibuprofen amine salt according to process conditions, the melting point of the produced dextranamine salt is very low (122°C-130°C) and the level of levo isomer in the dexibuprofen obtained by hydrolysis and acidification significantly exceeds the acceptable standard. The applicant has found in an industrial production that the remaining water after washing with water during the process of reusing toluene causes the melting point of dextro-amine salt to be unexpectedly equal to the acceptable standard. This shows that a small amount of water is required for cleavage. Applicant has found through a variety of innovative experiments that too much water (over 0.02 times the ibuprofen dosage amount, the unit of water is L and the unit of ibuprofen is kg) can dissolve amine salt, resulting in a reduced amount of product and lower yield (normal yield is 92%, yield is reduced below 88% with excess water). With too little water (less than 0.01 times the ilbuprofen dosage, the unit of water is L and the unit of ibuprofen is kg), the melting point of the amine salt is very low (the acceptable standard is 135-140°C and the lowest is 125°C), making the product non-standard. Finally, through the experiments, we found that the amount of water required to produce amine salt and the ratio of the volume of purified water to the weight of ibuprofen is 0.01-0.02L:1kg, i.e. the purified water is added according to this ratio when switching from the reaction of raw and auxiliary materials at elevated temperature to crystallization on cooling. Finally, the molar yield of dexibuprofen is high and the melting point of the dextroamine salt reaches the acceptable standard of 135-140°C.

DESCRIPTION OF THE DRAWINGS

Figure 1 is the flow chart of a process for the production of dexibuprofen according to the present invention;

Fig. 2 is the infrared spectrum of dexibuprofen produced in embodiment 1 of the present invention;

Fig. 3 is the chromatogram of dexibuprofen produced in embodiment 1 of the present invention;

Fig. 4 is the related substance chromatogram of dexibuprofen produced in Embodiment 1 of the present invention.

EMBODIMENTS

EMBODIMENT 1 A process for the manufacture of dexibuprofen, comprising:

I. Preparation of amine salt:

1. Toluene with a process amount (2448L) was placed in a reaction vessel according to the feed ratio, and about 50L hydrochloric acid solution (14-18%) was added. It was stirred for over 10 minutes and allowed to stand for over 10 minutes to separate the hydrochloric acid layer. Then, about 200L of drinking water was added, stirred over 10 minutes, and allowed to stand over 10 minutes to separate the water layer.

2. 315 kg of ibuprofen and 216 kg of N-octyl-d-glucamine were used according to the feed ratio. The hole cover was sealed. It was stirred and heated to the temperature of 76-80°C and the temperature was maintained over 0.5 hour.

3. The material was transferred to an amine salt crystallization kettle. About 4.5L of purified water was added and cooled to crystallize. After the temperature dropped to 18-22°C, the material was spun dry in a centrifuge (1015 minutes), washed once with toluene (30-50L) and rinsed once (30-40L).

The material was bagged and weighed to obtain a wet product of amine salt. The wet product of amine salt was placed in a dryer with the water temperature set at 85-95°C and the degree of vacuum <= -0.09 MPa. After drying for 3-6 hours, the material was unloaded, bagged and weighed. A 20-30g sample was taken with a sampling bottle and sent for testing to determine the melting point. The melting point was determined with a melting point tester and is 135°C-140°C.

II. Hydrolysis reaction:

1. 936L of drinking water, 59.4kg of potassium hydroxide and 300kg of a batch of dexibuprofen-NOctyl-d-glucamine salt produced in the above process step were added to a hydrolysis reaction vessel according to the feed ratio, and then the hole cover was sealed.

2. After heating to 45-55°C and conducting the reaction for 40-60 minutes, the material was transferred to a hydrolysis freezing kettle. Ice brine was opened to cool below 20°C.

3. The frozen material was spun dry in a centrifuge and washed once with water (30-50L). The centrifugal solution and wash water were aspirated into an acidification kettle. The filter cake after centrifugation was N-octyl-d-glucamine and was dried with the water temperature from the jacket of the dryer at =95°C and the degree of vacuum at 3/15

became. A sample was taken for testing. The material was then unloaded and weighed.

III. Acidification reaction:

1. After the temperature was raised to 45-55°C, the material in the acidification kettle was dropwise acidified with hydrochloric acid having a concentration of 14-18%. The final pH was 1-2 and the reaction was carried out at the maintained temperature for 0.5-1 hour.

2. After the temperature dropped below 30°C, the material was discharged and spun dry by centrifugation (8-10 min) and washed with water to pH 5-7. After being spun dry, it was bagged and weighed. The weight of each batch of wet crude product should be not less than 55kg (based on 135kg amine salt) and the molar yield should be = 66%. The yield calculation method is: Crude Product Output + (Glucoseoctylamine Feed Rate x 206.28-293.4). In this embodiment, the wet crude product weight was 134 kg and the molar yield was 88.2%.

3. A 20-30g sample was taken to examine appearance and rt% (HPLC method). Appearance was off-white to light yellow.

IV. Refining of the crude product:

The crude product of dexibuprofen was used in 80% acetic acid (4+42%) in a dissolving vessel. The weight ratio of the described dexibuprofen crude product: 80% acetic acid (42%) was 1:1.4. In this process stage, different batches can be mixed when they are used. The weight of the raw product was kept under control at 330kg-450kg. The hole cover was opened and the crude dexibuprofen from the above process step and 1-2kg of activated charcoal were added. Then it was sealed and the temperature raised to 45-60°C and held for 0.5>1 hour. Thereafter, the material was pressure-filtered into the crystallization vessel, cooled to 0-5°C, spun dry by centrifugation, washed with purified water to pH=5-7 and spun dry in a centrifuge (8-10 min). Then, a 20-30g sample was taken in a polyethylene plastic bottle for examination of appearance and cl%. Appearance was white and cl-% was <0.008%. Then, it was placed in a drier with the temperature of the drier set at 35-40°C and the degree of vacuum set to EMBODIMENT EXAMPLE 2 A process for producing dexibuprofen, which comprises:

I. Preparation of amine salt:

1. Toluene with a process amount (2362.5L) was placed in a reaction kettle according to the feed ratio, and about 50L hydrochloric acid solution (14-18%) was added. It was stirred over 10 minutes and allowed to stand over 10 minutes to separate the hydrochloric acid layer. Then, about 200L of drinking water was added, stirred over 10 minutes, and allowed to stand over 10 minutes to separate the water layer.

2. 315 kg of ibuprofen and 204.75 kg of N-octyl-d-glucamine were used according to the feed ratio. The hole cover was sealed. It was stirred and heated to the temperature of 76-80°C and the temperature was maintained over 0.5 hour.

3. The material was transferred to an amine salt crystallization kettle. About 3.15L of purified water was added and cooled to crystallize. After the temperature dropped to 18-22°C, the material was spun dry in a centrifuge (10-15

minutes), washed once with toluene (30-50L) and rinsed once (30-40L).

The material was bagged and weighed to obtain a wet product of amine salt. The wet product of amine salt was placed in a dryer with the water temperature set at 85-95°C and the degree of vacuum <= -0.09MPa. After drying for 3-6 hours, the material was unloaded, bagged and weighed. A 20-30g sample was removed from a sampling bottle and sent for testing to determine the melting point. The melting point was determined with a melting point tester and is 135°C-140°C.

II. Hydrolysis reaction:

1. 882.35L of drinking water, 52.9kg of potassium hydroxide and 300kg of a batch of dexibuprofen N-octyl-d-glucamine salt produced in the above process step were added to a hydrolysis reaction vessel according to the feed ratio, and then the hole cover was sealed.

2. After heating to 45-55°C and conducting the reaction for 40-60 minutes, the material was transferred to a hydrolysis freezing kettle. Ice brine was opened to cool below 20°C.

3. The frozen material was spun dry in a centrifuge and washed once with water (30-50L). The centrifugal solution and wash water were aspirated into an acidification kettle. The filter cake after centrifugation was N-octyl-d-glucamine and was dried keeping the water temperature from the jacket of the dryer at =95°C and the vacuum degree at III. Acidification reaction:

1. After the temperature was raised to 45-55°C, the material in the acidification kettle was dropwise acidified with hydrochloric acid having a concentration of 14-18%. The final pH was 1-2 and the reaction was carried out at the maintained temperature for 0.5-1 hour.

2. After the temperature dropped below 30°C, the material was discharged and spun dry by centrifugation (8-10min) and washed with water to pH 5-7. After being spun dry, it was bagged and weighed. The weight of each batch of wet crude product should be not less than 55kg (based on 135kg amine salt) and the molar yield should be = 66%. The yield calculation method is: Crude Product Output + (Glucoseoctylamine Feed Rate x 206.28-293.4). In this embodiment, the wet crude product weight was 125 kg and the molar yield was 86.8%.

3. A 20-30g sample was taken for examination of appearance and rt% (HPLC method). Appearance was off-white to light yellow.

IV. Refining of Crude Product:

The crude product of dexibuprofen was used in 80% acetic acid (42%) in a dissolving kettle. The weight ratio of the described dexibuprofen crude product: 80% acetic acid (+2%) was 1:1.4. In this process stage, different batches can be mixed when they are used. The weight of the raw product was kept under control at 330kg-450kg. The hole cover was opened and the crude dexibuprofen from the above process step and 1-2 kg of activated charcoal were added. Then the dissolving vessel was closed and the temperature increased to 45-60°C and held for 0.51 hour. Thereafter, the material was pressure filtered into the crystallizer, cooled to 0-5°C, spun dry by centrifugation, washed with purified water to pH=5-7 and spun dry in a centrifuge (8-10 min). Then a 20-30g sample in a

Taken from polyethylene plastic bottle to check appearance and cl%. Appearance was white and cl-%<0.008%. Then it was placed in a drier, the temperature of the drier being adjusted to 35-40°C and the degree of vacuum to <= -0.09 MPa. The drying was carried out over 24 hours and the water was removed every 2-3 hours. Then the material was packed in a carton and weighed and transferred to the packing room where it was crushed, sieved and bagged, tied and packed separately.

EMBODIMENT 3 A method of manufacturing dexibuprofen, comprising:

I. Preparation of amine salt:

1. Toluene with a process amount (2520L) was placed in a reaction kettle according to the feed ratio, and about 50L hydrochloric acid solution (14-18%) was added. It was stirred for over 10 minutes and allowed to stand for over 10 minutes to separate the hydrochloric acid layer. Then, about 200L of drinking water was added, stirred for over 10 minutes, and allowed to stand for over 10 minutes to separate the water layer.

2. 315 kg of ibuprofen and 236.25 kg of N-octyl-d-glucamine were used according to the feed ratio. The hole cover was sealed. It was stirred and heated to a temperature of 76-80°C and the temperature was maintained for 0.5 hour.

3. The material was transferred to an amine salt crystallization kettle. About 6.3L of purified water was added and cooled to crystallize. After the temperature dropped to 18-22°C, the material was spun dry in a centrifuge (10-15 minutes), washed once with toluene (30-50L) and rinsed once (30-40L).

The material was bagged and weighed to obtain a wet product of amine salt. The wet product of amine salt was placed in a dryer with the water temperature set at 85-95°C and the degree of vacuum <= -0.09 MPa. After 3-6 hours of drying, the material was unloaded, bagged and weighed. A 20-30g sample was removed from a sampling bottle and sent for testing to determine the melting point. The melting point was determined with a melting point tester and is 135°C-140°C.

II. Hydrolysis reaction:

1. 916.7L of drinking water, 58.34kg of potassium hydroxide and 300kg of a batch of dexibuprofen N-octyl-d-glucamine salt produced in the above process step were added to a hydrolysis reaction vessel according to the feed ratio, and then the hole cover was sealed .

2. After being heated to 45-55°C and reacting for 40-60 minutes, the material was transferred to a hydrolysis freezing kettle. Ice brine was opened to cool below 20°C.

3. The frozen material was spun dry in a centrifuge and washed once with water (30-50L). The centrifugal solution and wash water were aspirated into an acidification kettle. The filter cake after centrifugation was N-octyl-d-glucamine and was dried with the water temperature from the jacket of the dryer at =95°C and the vacuum degree at II. acidification reaction:

1. After the temperature was raised to 45-55°C, the material in the acidification kettle was dropwise acidified with hydrochloric acid having a concentration of 14-18%. The

Final pH was 1-2 and the reaction was carried out at the maintained temperature for 0.5>1 hour.

2. After the temperature dropped below 30°C, the material was discharged and spun dry by centrifugation (8-10min) and washed with water to pH 5-7. After being spun dry, it was bagged and weighed. The weight of each batch of wet crude product should be not less than 55kg (based on 135kg amine salt) and the molar yield should be = 66%. The yield calculation method is: Crude Product Output + (Glucoseoctylamine Feed Rate x 206.28 + 293.4). In this embodiment, the wet crude product weight was 151 kg and the molar yield was 90.9%.

3. A 20-30g sample was taken for examination of appearance and rt% (HPLC method). Appearance was off-white to light yellow.

IV. Refining of the crude product:

The crude product of dexibuprofen was used in 80% acetic acid (4+2%) in the dissolving tank. The weight ratio of the described dexibuprofen crude product: 80% acetic acid (+2%) was 1:1.4. In this process stage, different batches can be mixed when they are used. The weight of the raw product was kept under control at 330kg-450kg. The hole cover was opened and the crude dexibuprofen from the above process step and 1-2kg of activated charcoal were added. Then the dissolving vessel was closed and the temperature increased to 45-60°C and maintained for 0.5-1 hour. Thereafter, the material was pressure filtered into a crystallizer, cooled to 0-5°C, spun dry by centrifugation, washed with purified water to pH=5-7 and spun dry in a centrifuge (8-10 min). Then a 20-30g sample was taken in a polyethylene plastic bottle for examination of appearance and cl%. Appearance was white and cl%<0.008%. Then, it was placed in a drier with the temperature of the drier set at 35-40°C and the degree of vacuum = -0.09 MPa. The drying was carried out over 24 hours and the water was removed every 2-3 hours. Then the material was packed and weighed in the carton and transferred to the packing room where it was crushed, sieved and bagged, tied and packed separately.

COMPARATIVE EXAMPLE 1

The comparative example is the same as example 1, with the difference that no purified water is added when changing from the reaction of raw and auxiliary materials at elevated temperature to crystallization on cooling. Dexibuprofen-N-octyl-d-glucamine salt produced by a salt formation reaction has a low melting point of 122°C-130°C determined with a melting point tester.

EXPERIMENTAL EXAMPLE 1

|. The dexibuprofen prepared in Example 1 was subjected to product testing. The product lot number is “Product Lot Number: C102-1906007M” and the test results are shown in Table 1.

II. Table 1

Examination items Requirement for examination standard Examination results

| The product is white or off-white. . | Properties of bene crystalline powder White crystalline powder

A. The Infrared Absorption Spectrum _

of this product should be compatible with the Dexibu | Consistent with the profen reference substance | requirement/regulations are correct

B. The retention time of the main peak

of sample should be checked for ver- _

applied substances with the retenti-| In accordance with the

Identity of the main peak of the Dexibu- | Requirement

match profen reference substance. C. There is a maximum absorbance at 265 and 273 nm, a minimum | In agreement with the absorption at 245 and 271 nm and ei- | Requirement for a shoulder peak at 259 nm.

Absorption coefficient 425-470 446

Specific rotation +56° to +60° +58.2°

Melting point 48-53°C (and the melting range 50.6-51.9°C

does not exceed 2°C) Chloride <0.01% <0.01% a-Methyl-4-butylphenylacetic acid must not exceed 0.3% A single impurity peak

Not established

Related Substances |must not exceed 0.3% 0.01% Sum of peak areas of each impurity must not exceed 0.7% 0.02% Levibuprofen <1.0% 0.40% Toluene <890ppm Not detected Heavy metal <0.002% <0.002% Loss on drying <0.5 % 0.04% residue on ignition <0.1% 0.03% content (calculated as 98.5---101.0% 100.0%

dry product) Conclusion: The product has been tested according to the second part of the 2015 edition of the "Chinese Pharmacopoeia" and the results meet the requirement.

1. The infrared spectrum of the dexibuprofen prepared in Example 1 is shown in FIG. As can be seen from Fig. 2, the infrared absorption spectrum of this product agrees with the spectrum of the regular dexibuprofen reference substance.

2. The UV spectrum of the dexibuprofen produced in Example 1 is shown in FIG. As can be seen from Fig.3, there is a maximum absorption at 265 and 273 nm, a minimum absorption at 245 and 271 nm and a shoulder peak at 259 nm.

3. Check for related substances: The final product obtained in Example 1 was taken out, and chloroform was added to obtain a solution containing 100 mg per 1 ml as a sample solution. An appropriate amount was accurately weighed and trichloromethane was added to dilute to obtain a solution containing 1.0 mg per 1 ml as a control solution. The chromatogram of related substances is shown in Fig.4. As can be seen from Fig. 4, the retention time of the main peak from the sample under the examination item "Check for related substances" agrees with the retention time of the main peak of the regular dexibuprofen reference substance.

In summary, dexibuprofen is the standard as per the present

successfully manufactured the invention. Dexibuprofen in Examples 2-3 is also standard.

II. Statistically, as shown in Table 2, the melting point of dextroamine salt and the molar yield of dexibuprofen are high in Examples 1-3 and Comparative Example 1.

Table 2

group volume of purified | Melting Point of Molar Yield

Water: weight of Ibu- | dextroamine salt

profen Example 1 0.014: 1 135°C-140°C 88.2% Example 2 0.010: 1 135°C-140°C 86.8% Example 3 0.020: 1 135°C-140°C 90.9% Comparative Example 1 0 122°C- 130°C /

From Table 2 it can be seen that precise control of the amount of water is very important for the cleavage process. Finally, we have found through experiments that the ratio of the volume of added purified water to the weight of ibuprofen during the manufacture of amine salt is 0.01-0.02L: 1 kg, this proportion of purified water being added when from the Reaction of raw and auxiliary materials at elevated temperature is switched to crystallization when cooling down. Finally, the molar yield of dexibuprofen is high (the molar yield is 86.8%-90.9%) and the melting point of the dextroamine salt reaches the acceptable standard of 135-140°C.

The description represents only preferred embodiments of the present invention and is not intended to limit the present invention. Any modifications, equivalent substitutions and improvements made within the spirit and principle of the present invention are within the scope of the present invention.

Claims (10)

Expectations 1. Process for the production of dexibuprofen, characterized in that the process comprises the following steps: Step 1: Production of dexibuprofen-N-octyl-d-glucamine salt by a salt formation reaction, with toluene being placed in a reaction vessel, ibuprofen and n -Octyl-d-glucamine are added and heated with stirring to 76-80°C, the reaction is carried out over 0.5 hour at maintained temperature and the material is then transferred to an amine salt crystallization kettle and with addition of purified water cooling until crystallized, after which the temperature is lowered to 18-22°C, centrifugation and separation, washing and drying are performed to obtain dexibuprofenn-octyl-d-glucamine salt; wherein the feeding ratio of ibuprofen: N-octyl-dglucamine: toluene: purified water is 1:0.65-0.75:7.5-8:0.01-0.02, the unit of ibuprofen and N-octyl -d-glucamine in this ratio is kg and the unit of toluene and purified water is L; Step 2: Hydrolysis reaction to precipitate N-octyl-d-glucamine, wherein the hydrolysis reaction is carried out by adding the dexibuprofen-n-octyl-d-glucamine salt obtained in Step 1 into an alkaline saline solution to make n-octyl-d- glucamine precipitates and is removed; Step 3: Acidification reaction to precipitate dexibuprofen, the pH of the material obtained in step 2 after removing N-octyl-d-glucamine is adjusted to 1-2 with hydrochloric acid, then the wet crude product of dexibuprofen after cooling and centrifugation is obtained and a finished product of dexibuprofen is obtained by refining. 2. Process for the preparation of dexibuprofen according to claim 1, characterized in that in described step 1, when toluene is initially charged in the reaction vessel, a hydrochloric acid solution with a concentration of 14-18% is added, stirred for 10 minutes and left to stand for 10 minutes is used to separate the hydrochloric acid layer; then adding water, stirring for 10 minutes, and allowing to stand for 10 minutes to separate the water layer. 3. Process for the production of dexibuprofen according to claim 1, characterized in that the sequence of centrifuging and separating and washing in step 1 described is: the material is spun dry in a centrifuge, then washed with toluene, which is also rinsed with toluene. 4. Process for the production of dexibuprofen according to claim 1, characterized in that the course of drying in step 1 is: in a dryer, the water temperature is set to 85-95°C and the degree of vacuum to <= -0.09 MPa and that Drying is carried out for 3-6 hours. 5. The method for producing dexibuprofen according to claim 1, characterized in that the course of the hydrolysis reaction in step 2 is: the dexibuprofen-N-octyl-d-glucamine salt obtained in step 1 is added to drinking water and potassium hydroxide in the hydrolysis reaction vessel, heated to 45-55°C and allowed to react for 40-60 minutes, transferring the material to a hydrolysis freezing kettle, opening an ice brine to cool it to below 20°C and aspirating the solution and wash water after centrifugation into the acidification kettle , wherein the filter cake is N-octyl-dglucamine and is dried. 6. The method for producing dexibuprofen according to claim 5, characterized in that the feeding ratio of dexibuprofen, potassium hydroxide and drinking water is 170-180kg: 30-35kg: 500-550L. 7. Process for the production of dexibuprofen according to claim 1, characterized in that the course of the hydrolysis reaction in step 3 is: the material obtained in step 2 after removing N-octyl-d-glucamine is fed to an acidification vessel and on heated to 45-55°C, then acidified with 14-18% hydrochloric acid, the final pH being 1-2 and the reaction being carried out at the maintained temperature for 0.5-1 hour; the material is cooled to below 30°C and spun dry by centrifugation and washed with water until the pH is 5-7, the spin dry yielding a wet crude product of dexibuprofen. 8. Process for the production of dexibuprofen according to claim 1, characterized in that the course of refining of the obtained wet crude product of dexibuprofen in step 3 is: the wet crude product of dexibuprofen is treated with 78%-82% acetic acid in a weight ratio of 1:1 ,4 is placed in the dissolving vessel and this is closed after additions of an appropriate amount of activated carbon, raising the temperature to 45-60°C and maintaining it for 0.5>1 hour, then the material is filtered under pressure in the crystallization vessel, cooled to 0-5°C and spun dry in a centrifuge and washed with purified water until pH 5-7 and spun dry by centrifugation; then the material is put into the drier, with the temperature of the drier being set at 35-40°C, and the degree of vacuum being <= -0.09MPa, and the drying is carried out over 24 hours, thereby obtaining the finished product of dexibuprofen . 9. The process for producing dexibuprofen according to claim 1, characterized in that the toluene mother liquor remaining in step 1 after amine salt reaction is subjected to extraction with acid and neutralization with alkali to recycle N-octyl-d-glucamine. 10. Process for the preparation of dexibuprofen according to claim 1, characterized in that the toluene mother liquor remaining after the amine salt reaction in step 1 is first subjected to acid extraction with 14-18% hydrochloric acid, then the acidic water layer is separated and Sodium hydroxide adjusted to pH=12, cooled, spun dry by centrifugation and washed with water until pH=8-9 to recover N-octyl-dglucamine; after which sodium hydroxide and drinking water are added to the toluene mother liquor, the alkaline water layer is separated, adjusted to pH=1-2 after racemization treatment with hydrochloric acid, extracted with toluene, cooled and centrifuged to obtain racemic ibuprofen again. 4 sheets of drawings