CN108948017A - A kind of purification process of folic acid - Google Patents
A kind of purification process of folic acid Download PDFInfo
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- CN108948017A CN108948017A CN201710368978.7A CN201710368978A CN108948017A CN 108948017 A CN108948017 A CN 108948017A CN 201710368978 A CN201710368978 A CN 201710368978A CN 108948017 A CN108948017 A CN 108948017A
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- C07D475/00—Heterocyclic compounds containing pteridine ring systems
- C07D475/02—Heterocyclic compounds containing pteridine ring systems with an oxygen atom directly attached in position 4
- C07D475/04—Heterocyclic compounds containing pteridine ring systems with an oxygen atom directly attached in position 4 with a nitrogen atom directly attached in position 2
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Abstract
The invention belongs to field of compound preparation, a kind of purification process of folic acid is disclosed, the sour item for disposal that folic acid crude product carries out after acid treating carries out alkali refining under the conditions of pH6~6.5, adjusts acid crystal, dry folic acid finished product.The purification process of folic acid of the present invention, the pH value that alkali refining is controlled after acid treating is 6~6.5, carries out alkali refining step under weak acid environment, and condition is milder, reduces the hydrolyzed possibility for generating impurity A of folic acid, improves folic acid product yield and purity.It tests and shows to effectively reduce the content of impurity A using the purification process of folic acid of the present invention, while also reducing the content of impurity D compared with traditional folic acid purification process, improve the yield and purity of folic acid finished product.
Description
Technical field
The invention belongs to field of compound preparation, and in particular to a kind of purification process of folic acid, more particularly, to a kind of drop
The purification process of low folic acid impurity A (N- (4- aminobenzoyl)-Pidolidone) content.
Background technique
Folic acid is a kind of basic kind of vitamin, substance necessary to being body cell growth and breeding, to cell
The synthesis of merisis and nucleic acid, amino acid, protein plays an important role.Human body, which lacks folic acid, can lead to the different of red blood cell
Often, the increase of immature cell, anaemia and white blood cell are reduced；Pregnant woman's shortage folic acid is likely to result in occurring when fetal birth low
Weight, harelip, heart defect etc..
There are many food containing folic acid, but since natural folic acid is extremely unstable, influence and occur vulnerable to ultraviolet light, high temperature etc.
Oxidation, and folic acid biological availability is lower, so the folic acid that human body can really be obtained from food and few.The mankind are to folic acid
Dependent Demand is in commercial synthesis folic acid.The folic acid of commercial synthesis can keep stable within several months or several years, and it is easy to absorb,
Human body availability is about higher by one times of natural product or so.With the fast development in the fields such as medicine, food, the demand of folic acid
Also it increases sharply, has pushed the fast development of folic acid synthetic technology.
However, chemically synthesized folic acid crude product purity is often less high, need to be further purified, qualified leaf could be obtained
Sour finished product.The method that the purification process of folic acid generally uses acid treating and alkali refining to combine at present.The molten technique of acid is carried out first,
Crude product is dissolved with acid solution, dissolved crude product is obtained into sour extract through elutriation, filters pressing；Alkali soluble technique is carried out again, it is anti-in alkali soluble
It answers and adds water and stirs sour extract in tank, adjust pH value to 9.0~9.5 with lye at 90~100 DEG C, filters pressing obtains alkali soluble filtrate；
Alkali soluble filtrate is through adjusting the process for refining such as acid crystal, drying to get finished product.Such as the Chinese patent of 102432610 A of Publication No. CN
Disclosed folic acid purification process are as follows: folic acid crude product is dissolved using the dilute sulfuric acid of 25%-35%, by dissolved folic acid crude product through water
Analysis, filters pressing obtain sour extract；It recycles lye to carry out alkali soluble to sour extract, is heated to 90~102 DEG C, and adjust pH value with lye
To 9.0~9.5,1 hour is kept the temperature, filters pressing obtains alkali soluble filtrate after active carbon decoloring is added；Recycle diluted acid to lye carry out at
Salt refining obtains folic acid finished product.In addition the folic acid purification process of state's patent disclosure of 103102351 B of Publication No. CN are as follows: benefit
Folic acid crude product is dissolved with the hydrochloric acid of 15%-25%, into the dissolved folic acid crude product solution of gained plus water, blowing are centrifuged, directly
It connects drying and obtains sour extract；In alkali soluble reaction vessel, sour extract is mixed with solvent, and organic alkali solution is added to be adjusted to pH
9.0-10.0 is heated to 65-90 DEG C, adds adsorbent, keeps the temperature 0.5-2 hours at 65-90 DEG C, and filters pressing obtains alkali soluble filter
Liquid, the clear alkali soluble filtrate of gained are added in crystallization reaction container, 80~90 DEG C are heated to, with dilute hydrochloric acid tune pH
For 3.0-3.5, temperature is down to 55~60 DEG C, is centrifuged to obtain folic acid finished product.
Major impurity and troublesome impurity in folic acid purification process are impurity D (pteroic acid) and impurity A (N- (4- aminobenzoic
Acyl)-Pidolidone).Quality requirement impurity D content≤0.6% of folic acid finished product in European Pharmacopoeia, while Impurity A content≤
0.5%.And current folic acid purification process mostly controls impurity D (pteroic acid)≤0.6% in folic acid, and the content of impurity A is still
It is higher.
Summary of the invention
In view of this, it is an object of the invention to provide a kind of purification process of folic acid in view of the drawbacks of the prior art.This
The purification process of the folic acid is invented, alkali refining step carries out under weak acid benign environment, reduces the hydrolyzed possibility of folic acid, has
Conducive to the content for reducing impurity A, the purity of folic acid finished product is improved.
In order to achieve the object of the present invention, the present invention adopts the following technical scheme that.
A kind of purification process of folic acid, the sour item for disposal that folic acid crude product carries out after acid treating carry out under the conditions of pH6~6.5
Alkali refining adjusts acid crystal, dry folic acid finished product.
The purification process of folic acid of the present invention, the pH value that alkali refining is controlled after acid treating is 6~6.5, makes alkali refining
Step carries out under weak acid environment, and condition is milder, reduces the hydrolyzed possibility for generating impurity A of folic acid, receives folic acid finished product
Rate and purity improve.
Wherein, the acid treating is specially to dissolve folic acid crude product with acid solution, and be warming up to 35~45 DEG C and be dissolved to clarification
Afterwards, adsorbent is added, 25~35min of stirring is filtered, and water is added in filtrate, stirs 25~35min, stands 40~80min, it filters,
Obtain sour item for disposal.
Acid solution described in the step of acid treating can be at least one of sulfuric acid, hydrochloric acid.
Adsorbent described in the step of acid treating can be active carbon, diatomite or silica gel.
Further, the acid treating is preferably that acid solution is added in folic acid crude product, stirs lower dropwise addition acid solution, is warming up to
After 38-42 DEG C is dissolved to clarification, adsorbent is added, stirs 28-32min, filtering, filtrate adds water, stirs 28-32min, stands
50-70min, filtering obtain sour item for disposal；Wherein, based on g/ml, the mass volume ratio of the folic acid crude product and acid solution is
(2-4):4；The mass ratio of the adsorbent and folic acid crude product is (0.5-1.5): 45；Based on g/ml, the folic acid crude product and filter
The water quality volume ratio (4-8) that liquid is added: 100.
Further, the lower acid solution being added dropwise of acid solution and stirring that the step middle period acid crude of the acid treating is added
Volume ratio is preferably 1:1.
Further, the acid solution is preferably 45%~55% sulfuric acid or 20%-30% hydrochloric acid.In some embodiments
The acid solution is 50% sulfuric acid；In further embodiments, the acid solution is 45% sulfuric acid；In further embodiments,
The acid solution is 55% sulfuric acid；In further embodiments, the acid solution is 25% hydrochloric acid.
The purification process folic acid crude product of folic acid of the present invention carries out alkali refining after acid treating.The alkali refining is specific
It is added water and stirred for sour item for disposal, and is warming up to 75~85 DEG C, be adjusted to pH 6.0~6.5 with aqueous slkali, adsorbent, stirring is added
25~35min, filtering.
Wherein, the aqueous slkali can be sodium carbonate, sodium bicarbonate, ammonium hydroxide, sodium hydroxide, hydroxide during alkali refining
At least one of potassium.
The adsorbent is preferably active carbon, diatomite, at least one in silica gel during alkali refining of the present invention
Kind.
Further, the alkali refining is preferably in sour item for disposal plus water, stirring are warming up to 78-82 DEG C, use alkali soluble
Liquid adjusts pH to 6.0~6.5, and adsorbent is added, and stirs 28-32min, filtering；Wherein, based on g/ml, it is described acid item for disposal with
The mass volume ratio of water is (0.5-1.5): 30；The mass ratio of the adsorbent and sour item for disposal is (0.5-1.5): 10.
Further, the aqueous slkali is preferably 5-15% sodium carbonate liquor, 5-15% sodium bicarbonate solution, 5-15% ammonia
Water, 5-15%NaOH solution or 5-15%KOH solution.
The aqueous slkali is 10% sodium carbonate liquor in some embodiments.The aqueous slkali is in some embodiments
10% ammonia spirit.The aqueous slkali is 10% sodium bicarbonate solution in some embodiments.The alkali in some embodiments
Solution is 10%NaOH solution.The aqueous slkali is 10%KOH solution in some embodiments.
Further, the aqueous slkali is preferably 10% sodium carbonate liquor.
The purification process of folic acid of the present invention collected after alkali refining filtrate tune acid crystal, dry available folic acid at
Product.It is described that acid crystal, the dry filtrate for specially collecting alkali refining is adjusted to be heated to 75~85 DEG C, pH to 3.0 is adjusted with acid solution
~4.0, stirring is cooled to 65~75 DEG C, filters after 25~35min, dry.
Wherein, it is described adjust acid crystal, drying step described in acid solution be preferably sulfuric acid, hydrochloric acid, in acetic acid at least
It is a kind of.
Further, described to adjust acid crystal, the dry filtrate for preferably collecting alkali refining at 78-82 DEG C with acid solution tune
PH to 3.0~3.5 is saved, stirring is cooled to 68~72 DEG C, filters after about 28-32min, 40-60 DEG C of drying.
Further, the tune acid crystal, acid solution is preferably 3-8% dilute sulfuric acid, 7-15% salt described in drying steps
Acid or 30-40% acetic acid solution.The acid solution is 5% dilute sulfuric acid in some embodiments.The acid in some embodiments
Solution is 10% hydrochloric acid.The acid solution is 35% acetic acid solution in some embodiments.
Further, it is described adjust acid crystal, drying step described in acid solution be preferably 5% dilute sulfuric acid.
As shown from the above technical solution, the present invention provides a kind of purification process of folic acid, folic acid crude product carries out acid treating
Sour item for disposal afterwards carries out alkali refining under the conditions of pH6~6.5, adjusts acid crystal, dry folic acid finished product.Folic acid of the present invention
Purification process, after acid treating control alkali refining pH value be 6~6.5, carry out alkali refining step under weak acid environment,
Condition is milder, reduces the hydrolyzed possibility for generating impurity A of folic acid, improves folic acid product yield and purity.Experiment show with
Traditional folic acid purification process is compared, and the content of impurity A is effectively reduced using the purification process of folic acid of the present invention, simultaneously
The content of impurity D is also reduced, the yield and purity of folic acid finished product are improved.
Specific embodiment
The invention discloses a kind of purification process of folic acid.Those skilled in the art can use for reference present disclosure, suitably change
Into realization of process parameters.In particular, it should be pointed out that all similar substitutions and modifications are aobvious for a person skilled in the art
And be clear to, they are considered as being included in the present invention.Method and product of the invention has passed through preferred embodiment and has carried out
Description, related personnel obviously can not depart from the content of present invention, method described herein is modified in spirit and scope or
Appropriate changes and combinations carry out implementation and application the technology of the present invention.
For a further understanding of the present invention, below in conjunction with the embodiment of the present invention, to the technical side in the embodiment of the present invention
Case is clearly and completely described, it is clear that and described embodiments are only a part of the embodiments of the present invention, rather than all
Embodiment.Based on the embodiments of the present invention, those of ordinary skill in the art institute without making creative work
The every other embodiment obtained, shall fall within the protection scope of the present invention.
Unless otherwise specified, reagent involved in the embodiment of the present invention is commercial product, can pass through business canal
Road purchase obtains.
Embodiment 1
Acid treating: (detection of pharmacopeia HPLC method, folic acid purity 90.8%, Impurity A content 3.2% are miscellaneous for 360g folic acid crude product
Matter D content 2.6%) 50% sulfuric acid of 240mL is added, continue that 50% sulfuric acid about 240mL is added dropwise under stirring, is warming up to 40 DEG C of dissolutions
To clarification, active carbon 8g is added, stirs 30min, filtering, distilled water 6L is added in filtrate, stirs 30min, stands 1h, and filtering obtains
Obtain sour item for disposal.
Alkali refining: being added 7.2L distilled water in sour item for disposal, stirring is warming up to 80 DEG C, adjusts pH with 10% sodium carbonate liquor
6.0, active carbon 25g is added, stirs 30min, filtering.
It adjusts acid crystal: filtrate is heated to 80 DEG C, adjust pH 3.5 with 5% dilution heat of sulfuric acid, stirring is cooled to 70
DEG C, it is filtered after about 30min, 50 DEG C of drying obtain folic acid finished product.Yield 82%, HPLC detect folic acid purity 99.78%, impurity A
It is not detected, impurity D 0.038%.
Embodiment 2
Acid treating: (detection of pharmacopeia HPLC method, folic acid purity 90.8%, Impurity A content 3.2% are miscellaneous for 360g folic acid crude product
Matter D content 2.6%) 45% sulfuric acid of 240mL is added, continue that 45% sulfuric acid of 240mL is added dropwise under stirring, is warming up to 40 DEG C and is dissolved to
After clarification, active carbon 8g is added, stirs 30min, filtering, distilled water 6L is added in filtrate, stirs 30min, stands 1h, and filtering obtains
Sour item for disposal.
Alkali refining: being added 7.2L distilled water in sour item for disposal, stirring is warming up to 80 DEG C, adjusts pH with 10% ammonia spirit
6.5, active carbon 25g is added, stirs 30min, filtering.
It adjusts acid crystal: filtrate is heated to 80 DEG C, adjust pH 3.5 with 5% dilution heat of sulfuric acid, stirring is cooled to 70
DEG C, it is filtered after about 30min, 50 DEG C of drying obtain folic acid finished product.Yield 83%, HPLC detect folic acid purity 99.80%, impurity A
It is not detected, impurity D 0.029%.
Embodiment 3
Acid treating: (detection of pharmacopeia HPLC method, folic acid purity 90.8%, Impurity A content 3.2% are miscellaneous for 360g folic acid crude product
Matter D content 2.6%) 55% sulfuric acid of 240mL is added, continue that 55% sulfuric acid 240mL is added dropwise under stirring, is warming up to 40 DEG C and is dissolved to
After clarification, active carbon 8g is added, stirs 30min, filtering, distilled water 6L is added in filtrate, stirs 30min, stands 1h, and filtering obtains
Sour item for disposal.
Alkali refining: being added 7.2L distilled water in sour item for disposal, stirring is warming up to 80 DEG C, is adjusted with 10% sodium bicarbonate solution
Active carbon 25g is added in pH 6.5, stirs 30min, filtering.
It adjusts acid crystal: filtrate is heated to 80 DEG C, adjust pH 3.5 with 5% dilution heat of sulfuric acid, stirring is cooled to 70
DEG C, it is filtered after about 30min, 50 DEG C of drying obtain folic acid finished product.Yield 85%, HPLC detect folic acid purity 99.71%, impurity A
0.005%, impurity D 0.042%.
Embodiment 4
Acid treating: (detection of pharmacopeia HPLC method, folic acid purity 90.8%, Impurity A content 3.2% are miscellaneous for 360g folic acid crude product
Matter D content 2.6%) 25% hydrochloric acid of 240mL is added, continue that 25% hydrochloric acid 240mL is added dropwise under stirring, is warming up to 40 DEG C and is dissolved to
After clarification, diatomite 8g is added, stirs 30min, filtering, distilled water 6L is added in filtrate, stirs 30min, stands 1h, and filtering obtains
Sour item for disposal.
Alkali refining: being added 7.2L distilled water in sour item for disposal, stirring is warming up to 80 DEG C, adjusts pH with 10%NaOH solution
6.5, diatomite 25g is added, stirs 30min, filtering.
It adjusts acid crystal: filtrate is heated to 80 DEG C, adjust pH 3.5 with 10% hydrochloric acid solution, stirring is cooled to 70
DEG C, it is filtered after about 30min, 50 DEG C of drying obtain folic acid finished product.Yield 81%, HPLC detect folic acid purity 99.68%, impurity A
0.004%, impurity D 0.045%.
Embodiment 5
Acid treating: (detection of pharmacopeia HPLC method, folic acid purity 90.8%, Impurity A content 3.2% are miscellaneous for 360g folic acid crude product
Matter D content 2.6%) 25% hydrochloric acid of 240mL is added, continue that 25% hydrochloric acid 240mL of 240mL is added dropwise under stirring, is warming up to 40 DEG C
After being dissolved to clarification, silica gel 8g is added, stirs 30min, filtering, distilled water 6L is added in filtrate, stirs 30min, stands 1h, filtering
Obtain sour item for disposal.
Alkali refining: being added 7.2L distilled water in sour item for disposal, stirring is warming up to 80 DEG C, adjusts pH with 10%KOH solution
6.5, silica gel 25g is added, stirs 30min, filtering.
It adjusts acid crystal: filtrate is heated to 80 DEG C, adjust pH 3.5 with 35% acetic acid solution, stirring is cooled to 70
DEG C, it is filtered after about 30min, 50 DEG C of drying obtain folic acid finished product.Yield 83%, HPLC detect folic acid purity 99.73%, impurity A
0.006%, impurity D 0.051%.
Comparative example 1
Acid treating: using 500ml 18% hydrochloric acid by 100g folic acid crude product (pharmacopeia HPLC method detect, folic acid purity
90.8%, Impurity A content 3.2%, impurity D content 2.6%) dissolution, water is added into the dissolved folic acid crude product solution of gained, is put
Material, centrifugation, drying obtain sour extract.
Alkali refining: being added 3000ml deionized water in sour extract, ammonium hydroxide tune pH9 is added dropwise, is heated to 85 DEG C, repetition measurement
20g activated carbon is added after pH stablizes in pH value.After 85-90 DEG C keeps the temperature 1 hour, 55 DEG C are cooled to, filters pressing.
It adjusts acid crystal: filtrate is heated to 80 DEG C, the hydrochloric acid tune pH for being added dropwise 10% is 3.5.83.5 DEG C are warming up to, it is multiple
PH is surveyed after 3-3.5, is cooled to 57 DEG C.It is discharged to centrifuge to be directly centrifuged, then is eluted with the deionized water of 300ml 35-40 DEG C
Twice, 80 DEG C of drying, obtain folic acid fine work.Yield 80%, HPLC purity 99.4%, impurity A 0.31%, impurity D 0.09%.
Comparative example 2
Acid treating: (detection of pharmacopeia HPLC method, folic acid purity 90.8%, Impurity A content 3.2% are miscellaneous for 360g folic acid crude product
Matter D content 2.6%) 50% sulfuric acid of 240mL is added, continue that 50% sulfuric acid about 240mL is added dropwise under stirring, is warming up to 40 DEG C of dissolutions
To clarification, active carbon 8g is added, stirs 30min, filtering, distilled water 6L is added in filtrate, stirs 30min, stands 1h, and filtering obtains
Obtain sour item for disposal.
Alkali refining: being added 7.2L distilled water in sour item for disposal, stirring is warming up to 80 DEG C, adjusts pH with 10%NaOH solution
9.5, active carbon 25g is added, stirs 30min, filtering.
It adjusts acid crystal: filtrate is heated to 80 DEG C, adjust pH 3.5 with 5% dilution heat of sulfuric acid, stirring is cooled to 70
DEG C, it is filtered after about 30min, 50 DEG C of drying obtain folic acid finished product.Yield 77%, HPLC detect folic acid purity 98.7%, impurity A
0.41%, impurity D 0.35%.
Comparative example 3
Acid treating: (detection of pharmacopeia HPLC method, folic acid purity 90.8%, Impurity A content 3.2% are miscellaneous for 360g folic acid crude product
Matter D content 2.6%) 50% sulfuric acid of 240mL is added, continue that 50% sulfuric acid about 240mL is added dropwise under stirring, is warming up to 40 DEG C of dissolved clarifications
Afterwards, active carbon 8g is added, stirs 30min, filtering, distilled water 6L is added in filtrate, stirs 30min, stands 1h, and filtering obtains at acid
Reason product.
Alkali refining: being added 7.2L distilled water in sour item for disposal, stirring is warming up to 80 DEG C, adjusts pH with 10% sodium carbonate liquor
7, active carbon 25g is added, stirs 30min, filtering.
It adjusts acid crystal: filtrate is heated to 80 DEG C, adjust pH 3.5 with 5% dilution heat of sulfuric acid, stirring is cooled to 70
DEG C, it is filtered after about 30min, 50 DEG C of drying obtain folic acid finished product.Yield 76%, HPLC detect folic acid purity 98.6%, impurity A
0.39%, impurity D 0.38%.
Comparative example 4
Acid treating: (detection of pharmacopeia HPLC method, folic acid purity 90.8%, Impurity A content 3.2% are miscellaneous for 360g folic acid crude product
Matter D content 2.6%) 50% sulfuric acid of 240mL is added, continue that 50% sulfuric acid about 240mL is added dropwise under stirring, is warming up to 40 DEG C of dissolved clarifications
Afterwards, active carbon 8g is added, stirs 30min, filtering, distilled water 6L is added in filtrate, stirs 30min, stands 1h, and filtering obtains at acid
Reason product.
Alkali refining: being added 7.2L distilled water in sour item for disposal, stirring is warming up to 80 DEG C, is adjusted with 10% sodium carbonate liquor
Active carbon 25g is added in pH5, stirs 30min, filtering.
Adjust acid crystal: 80 DEG C adjust pH 3.5 with 5% dilution heat of sulfuric acid, and stirring is cooled to 70 DEG C, filters after about 30min,
50 DEG C of drying, obtain folic acid finished product.Yield 78%, HPLC detect folic acid purity 98.3%, impurity A 0.38%, impurity D
0.40%.
In conclusion compared with traditional folic acid purification process (comparative example 1-4), using the purifying of folic acid of the present invention
Method (embodiment 1-5) effectively reduces the content of impurity A and impurity D, improves the yield and purity of folic acid finished product.
Claims (10)
1. a kind of purification process of folic acid, which is characterized in that folic acid crude product carries out the sour item for disposal after acid treating in pH6~6.5
Under the conditions of carry out alkali refining, adjust acid crystal, dry folic acid finished product.
2. purification process according to claim 1, which is characterized in that the acid treating is specially to dissolve folic acid with acid solution
Crude product, and be warming up to 35~45 DEG C be dissolved to clarification after, be added adsorbent, stir 25~35min, filtering, filtrate be added water, stir
25~35min is mixed, 40~80min is stood, filtering obtains sour item for disposal.
3. purification process according to claim 2, which is characterized in that acid solution described in the step of the acid treating is sulphur
At least one of acid, hydrochloric acid；The adsorbent is at least one of active carbon, diatomite, silica gel.
4. purification process according to claim 2, which is characterized in that the acid treating is specially that folic acid crude product addition acid is molten
Liquid, stir it is lower acid solution is added dropwise, be warming up to 38-42 DEG C be dissolved to clarification after, adsorbent is added, stirs 28-32min, filters, filter
Liquid adds water, stirs 28-32min, stands 50-70min, and filtering obtains sour item for disposal；Wherein, based on g/ml, the folic acid crude product
Mass volume ratio with acid solution is (2-4): 4；The mass ratio of the adsorbent and folic acid crude product is (0.5-1.5): 45；By g/
The water quality volume ratio (4-8) that ml meter, the folic acid crude product and filtrate are added: 100；Preferably, the acid solution is 45%-
55% sulfuric acid or 20%-30% hydrochloric acid；It is furthermore preferred that being 45% sulfuric acid, 50% sulfuric acid, 55% sulfuric acid or 25% hydrochloric acid.
5. purification process according to claim 1, which is characterized in that the alkali refining is specially that sour item for disposal adds water to stir
It mixes, and is warming up to 75~85 DEG C, be adjusted to pH 6.0~6.5 with aqueous slkali, adsorbent is added, stir 25~35min, filtering.
6. purification process according to claim 5, which is characterized in that the aqueous slkali is sodium carbonate, sodium bicarbonate, ammonia
At least one of water, sodium hydroxide, potassium hydroxide；The adsorbent is active carbon, diatomite, at least one in silica gel
Kind.
7. purification process according to claim 5, which is characterized in that the alkali refining is specially to add in sour item for disposal
Water, stirring are warming up to 78-82 DEG C, adjust pH to 6.0~6.5 with aqueous slkali, adsorbent is added, and stir 28-32min, filtering；Its
In, based on g/ml, the mass volume ratio of the acid item for disposal and water is (0.5-1.5): 30；The adsorbent and sour item for disposal
Mass ratio is (0.5-1.5): 10；The aqueous slkali is 5-15% sodium carbonate liquor, 5-15% sodium bicarbonate solution, 5-15% ammonia
Water, 5-15%NaOH solution or 5-15%KOH solution, preferably 10% sodium carbonate liquor, 10% sodium bicarbonate solution, 10% ammonia
Water, 10%NaOH solution or 10%KOH solution.
8. purification process according to claim 1, which is characterized in that the tune acid crystal, dry specially collection alkali essence
The filtrate of system is heated to 75~85 DEG C, adjusts pH to 3.0~4.0 with acid solution, stirring is cooled to 65~75 DEG C, 25~35min
After filter, it is dry.
9. purification process according to claim 8, which is characterized in that it is described adjust acid crystal, drying step described in acid
Solution is at least one of sulfuric acid, hydrochloric acid, acetic acid.
10. purification process according to claim 8, which is characterized in that the tune acid crystal, dry specially collection alkali essence
The filtrate of system adjusts pH to 3.0~3.5 with acid solution at 78-82 DEG C, and stirring is cooled to 68~72 DEG C, filters after 28-32min,
40-60 DEG C of drying；Preferably, the acid solution 3-8% dilute sulfuric acid, 7-15% hydrochloric acid or 30-40% acetic acid solution；More preferably
, the acid solution is 5% dilute sulfuric acid, 10% hydrochloric acid or 35% acetic acid solution.
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| CN113816961A (en) * | 2021-08-17 | 2021-12-21 | 北京斯利安药业有限公司 | Folic acid synthesis method |
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| CN113816961A (en) * | 2021-08-17 | 2021-12-21 | 北京斯利安药业有限公司 | Folic acid synthesis method |
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