CN117986261A - Method for recycling nalmefene hydrochloride mother liquor - Google Patents
Method for recycling nalmefene hydrochloride mother liquor Download PDFInfo
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- CN117986261A CN117986261A CN202410390815.9A CN202410390815A CN117986261A CN 117986261 A CN117986261 A CN 117986261A CN 202410390815 A CN202410390815 A CN 202410390815A CN 117986261 A CN117986261 A CN 117986261A
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- Prior art keywords
- nalmefene hydrochloride
- mother liquor
- nalmefene
- recycling
- crude
- Prior art date
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- GYWMRGWFQPSQLK-OPHZJPRHSA-N (4r,4as,7as,12bs)-3-(cyclopropylmethyl)-7-methylidene-2,4,5,6,7a,13-hexahydro-1h-4,12-methanobenzofuro[3,2-e]isoquinoline-4a,9-diol;hydron;chloride Chemical compound Cl.N1([C@@H]2CC3=CC=C(C=4O[C@@H]5[C@](C3=4)([C@]2(CCC5=C)O)CC1)O)CC1CC1 GYWMRGWFQPSQLK-OPHZJPRHSA-N 0.000 title claims abstract description 83
- 229960000677 nalmefene hydrochloride Drugs 0.000 title claims abstract description 83
- 239000012452 mother liquor Substances 0.000 title claims abstract description 51
- 238000000034 method Methods 0.000 title claims abstract description 23
- 238000004064 recycling Methods 0.000 title claims abstract description 14
- 239000003513 alkali Substances 0.000 claims abstract description 16
- 239000012065 filter cake Substances 0.000 claims abstract description 15
- 238000001914 filtration Methods 0.000 claims abstract description 15
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims abstract description 14
- WJBLNOPPDWQMCH-MBPVOVBZSA-N Nalmefene Chemical compound N1([C@@H]2CC3=CC=C(C=4O[C@@H]5[C@](C3=4)([C@]2(CCC5=C)O)CC1)O)CC1CC1 WJBLNOPPDWQMCH-MBPVOVBZSA-N 0.000 claims abstract description 13
- 229960005297 nalmefene Drugs 0.000 claims abstract description 13
- 238000001035 drying Methods 0.000 claims abstract description 12
- 238000001816 cooling Methods 0.000 claims abstract description 10
- 238000002425 crystallisation Methods 0.000 claims abstract description 8
- 230000008025 crystallization Effects 0.000 claims abstract description 8
- 239000012043 crude product Substances 0.000 claims abstract description 7
- 238000010494 dissociation reaction Methods 0.000 claims abstract description 6
- 230000005593 dissociations Effects 0.000 claims abstract description 6
- 239000000706 filtrate Substances 0.000 claims abstract description 6
- 238000001953 recrystallisation Methods 0.000 claims abstract description 5
- 238000004090 dissolution Methods 0.000 claims abstract description 4
- 239000010413 mother solution Substances 0.000 claims abstract description 4
- 239000000843 powder Substances 0.000 claims abstract description 4
- 239000007788 liquid Substances 0.000 claims abstract description 3
- 238000000926 separation method Methods 0.000 claims abstract description 3
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims description 10
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 9
- 239000002904 solvent Substances 0.000 claims description 8
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 claims description 6
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 6
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 6
- 229910000029 sodium carbonate Inorganic materials 0.000 claims description 5
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 4
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims description 4
- NTIZESTWPVYFNL-UHFFFAOYSA-N Methyl isobutyl ketone Chemical compound CC(C)CC(C)=O NTIZESTWPVYFNL-UHFFFAOYSA-N 0.000 claims description 2
- UIHCLUNTQKBZGK-UHFFFAOYSA-N Methyl isobutyl ketone Natural products CCC(C)C(C)=O UIHCLUNTQKBZGK-UHFFFAOYSA-N 0.000 claims description 2
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 claims description 2
- 229910000027 potassium carbonate Inorganic materials 0.000 claims description 2
- 238000011084 recovery Methods 0.000 abstract description 9
- 238000000746 purification Methods 0.000 abstract description 4
- 239000012535 impurity Substances 0.000 abstract description 3
- 238000003889 chemical engineering Methods 0.000 abstract description 2
- 239000012847 fine chemical Substances 0.000 abstract description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 15
- 239000008213 purified water Substances 0.000 description 9
- 238000003756 stirring Methods 0.000 description 9
- 238000006243 chemical reaction Methods 0.000 description 8
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 6
- 238000004128 high performance liquid chromatography Methods 0.000 description 6
- 239000000047 product Substances 0.000 description 5
- 238000010438 heat treatment Methods 0.000 description 4
- 239000012458 free base Substances 0.000 description 3
- 238000010992 reflux Methods 0.000 description 3
- 230000001105 regulatory effect Effects 0.000 description 3
- 239000007787 solid Substances 0.000 description 3
- 206010008118 cerebral infarction Diseases 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 238000000605 extraction Methods 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 229960004127 naloxone Drugs 0.000 description 2
- UZHSEJADLWPNLE-GRGSLBFTSA-N naloxone Chemical compound O=C([C@@H]1O2)CC[C@@]3(O)[C@H]4CC5=CC=C(O)C2=C5[C@@]13CCN4CC=C UZHSEJADLWPNLE-GRGSLBFTSA-N 0.000 description 2
- 229940005483 opioid analgesics Drugs 0.000 description 2
- 239000002994 raw material Substances 0.000 description 2
- 238000007670 refining Methods 0.000 description 2
- 208000007848 Alcoholism Diseases 0.000 description 1
- 206010002091 Anaesthesia Diseases 0.000 description 1
- LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 description 1
- 201000006474 Brain Ischemia Diseases 0.000 description 1
- 206010008120 Cerebral ischaemia Diseases 0.000 description 1
- 206010010071 Coma Diseases 0.000 description 1
- 206010019196 Head injury Diseases 0.000 description 1
- 208000012488 Opiate Overdose Diseases 0.000 description 1
- 229940123257 Opioid receptor antagonist Drugs 0.000 description 1
- 208000004756 Respiratory Insufficiency Diseases 0.000 description 1
- 206010038678 Respiratory depression Diseases 0.000 description 1
- 208000007271 Substance Withdrawal Syndrome Diseases 0.000 description 1
- 208000030886 Traumatic Brain injury Diseases 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 201000007930 alcohol dependence Diseases 0.000 description 1
- 230000037005 anaesthesia Effects 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 208000026106 cerebrovascular disease Diseases 0.000 description 1
- 238000010835 comparative analysis Methods 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 238000007865 diluting Methods 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 235000019441 ethanol Nutrition 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 229950010675 nalmefene hydrochloride dihydrate Drugs 0.000 description 1
- 210000005036 nerve Anatomy 0.000 description 1
- 239000003401 opiate antagonist Substances 0.000 description 1
- 231100000572 poisoning Toxicity 0.000 description 1
- 230000000607 poisoning effect Effects 0.000 description 1
- 230000002980 postoperative effect Effects 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 238000003908 quality control method Methods 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 230000035939 shock Effects 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 208000020431 spinal cord injury Diseases 0.000 description 1
- 230000002618 waking effect Effects 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D489/00—Heterocyclic compounds containing 4aH-8, 9 c- Iminoethano-phenanthro [4, 5-b, c, d] furan ring systems, e.g. derivatives of [4, 5-epoxy]-morphinan of the formula:
- C07D489/06—Heterocyclic compounds containing 4aH-8, 9 c- Iminoethano-phenanthro [4, 5-b, c, d] furan ring systems, e.g. derivatives of [4, 5-epoxy]-morphinan of the formula: with a hetero atom directly attached in position 14
- C07D489/08—Oxygen atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/07—Optical isomers
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention discloses a method for recycling nalmefene hydrochloride mother liquor, which relates to the technical field of fine chemical engineering and comprises the following steps: adding alkali into the refined nalmefene hydrochloride mother solution for dissociation, and filtering to obtain nalmefene free alkali; after recrystallization, hydrochloric acid salifying to obtain mother liquor for recovering nalmefene hydrochloride crude product; and (3) combining the crude nalmefene hydrochloride recovered from the mother liquor with the crude nalmefene hydrochloride, carrying out purified hydrothermal dissolution, cooling crystallization, carrying out solid-liquid separation to obtain a filter cake and a filtrate, drying the filter cake to obtain white crystalline powder, namely the nalmefene hydrochloride monohydrate, wherein the filtrate is refined mother liquor containing the nalmefene hydrochloride. According to the scheme, the nalmefene hydrochloride refined mother liquor is continuously utilized after recovery and purification, the yield of nalmefene hydrochloride is obviously improved, and the nalmefene hydrochloride monohydrate with single impurity less than 0.1% and purity more than 99.9% and meeting the pharmacopoeia quality standard can be prepared.
Description
Technical Field
The invention relates to the technical field of fine chemical engineering, in particular to a method for recycling nalmefene hydrochloride mother liquor.
Background
Nalmefene hydrochloride is an endogenous opioid receptor antagonist with high selectivity and specificity developed by Baxter Healthcare Corporation and approved by the U.S. Food and Drug Administration (FDA) for use in reversing the effects of opioids, either completely or partially, including respiratory depression caused by natural or synthetic opioids in month 4 of 1995. The naloxone has become a substitute for naloxone in clinic, and is mainly used for treating nerve functional damage diseases such as known or suspected opioid overdose or poisoning, acute craniocerebral and spinal cord injury, cerebral ischemia, cerebral infarction, etc., coma, shock, postoperative anesthesia and waking, alcoholism, drug withdrawal, etc. The prior bulk drug production mainly comprises nalmefene hydrochloride monohydrate, and the structural formula of the nalmefene hydrochloride monohydrate is as follows:
。
CN104513251A reports a preparation method of nalmefene hydrochloride, but the yield is about 52% -64%, and about 45% of the product is lost to the mother liquor after refining, so that the material is wasted and the cost is extremely high.
CN104093721a discloses a method for recovering nalmefene hydrochloride, adding bisulphite into mother liquor, purifying and recovering to obtain nalmefene; in the scheme, two solvents such as dichloromethane and the like are used for extraction, a large amount of water in the mother liquor is required to be concentrated, the process is complex, and the nalmefene is degraded due to long-time high-temperature concentration.
CN104211707a discloses a method for preparing nalmefene hydrochloride dihydrate and also discloses a method for recovering mother liquor, because the recovering method still needs to distill the aqueous mother liquor, and meanwhile, the second solvent dichloromethane is also adopted for extraction, the recovering cost is higher, and the quality control of recovered products is not facilitated.
Therefore, it is necessary to develop a method for recovering and applying mother liquor which can meet the quality requirements of raw materials and solve the above technical problems at low cost.
Disclosure of Invention
In order to solve the defects of the prior art, the invention provides a method for recycling the nalmefene hydrochloride mother liquor, which has the advantages of low cost and simple operation, and the nalmefene hydrochloride refined mother liquor can be continuously recycled and reused and can meet the demands of raw materials.
In order to achieve the object of the invention, the following scheme is adopted:
The method for recycling the nalmefene hydrochloride mother liquor comprises the following steps:
Adding alkali into the refined nalmefene hydrochloride mother solution for dissociation, and filtering to obtain nalmefene free alkali; after recrystallization, hydrochloric acid salifying to obtain mother liquor for recovering nalmefene hydrochloride crude product;
And (3) combining the crude nalmefene hydrochloride recovered from the mother liquor with the crude nalmefene hydrochloride, carrying out purified hydrothermal dissolution, cooling crystallization, carrying out solid-liquid separation to obtain a filter cake and a filtrate, and drying the filter cake to obtain white crystalline powder, wherein the white crystalline powder is nalmefene hydrochloride monohydrate, and the filtrate is refined mother liquor containing nalmefene hydrochloride.
Further, the alkali adopted for adding alkali for dissociation is one or more of sodium bicarbonate, sodium carbonate, potassium carbonate, sodium hydroxide and potassium hydroxide.
Further, the solvent for recrystallization is one or more of methanol, ethanol, isopropanol, acetone, methyl ethyl ketone, methyl isobutyl ketone.
Further, the dissolution temperature of the purified water is 60-80 ℃.
Further, the amount of the purified water is 0.8-1.5 times of the weight of the mother liquor recovered nalmefene hydrochloride crude product and the weight of the mother liquor recovered nalmefene hydrochloride crude product after being combined.
Further, the temperature of cooling crystallization is 0-30 ℃.
Further, the temperature of the filter cake drying is 40-60 ℃.
Further, the recovery and purification steps of the nalmefene hydrochloride refined mother liquor are as follows: diluting the nalmefene hydrochloride refined mother liquor by adding water, adding alkali for dissociation, adjusting the pH value to 8-9, and filtering to obtain nalmefene free alkali; the nalmefene free alkali is recrystallized by a solvent, and then hydrochloric acid is added to form salt after cooling, and mother solution is obtained after filtration and drying to recover crude nalmefene hydrochloride.
Further, the proportion of water dilution is 3-10 times of the weight of the nalmefene hydrochloride refined mother liquor.
The invention has the beneficial effects that: the provided recycling method realizes the recycling and purification and refining, continuously utilizes the refined mother liquor of nalmefene hydrochloride, remarkably improves the yield of nalmefene hydrochloride, and can prepare the nalmefene hydrochloride monohydrate with single impurity less than 0.1% and purity more than 99.9% and meeting the pharmacopoeia quality standard.
Drawings
FIG. 1 is a schematic flow chart of a method for recycling nalmefene hydrochloride mother liquor;
FIG. 2 is an HPLC profile of crude nalmefene hydrochloride in example 1;
FIG. 3 is an HPLC chart of a nalmefene hydrochloride purification mother liquor of example 4;
FIG. 4 is an HPLC chart of crude nalmefene hydrochloride recovered from the mother liquor of example 4;
FIG. 5 is an HPLC chart of the nalmefene hydrochloride monohydrate product obtained in example 4.
Detailed Description
Example 1
104G of crude nalmefene hydrochloride is transferred into a reaction kettle, as shown in figure 2, the purity of the crude nalmefene hydrochloride is 99.54%, 104g of purified water is added into the reaction kettle, the temperature is raised to 80 ℃ to dissolve clear, the temperature is slowly lowered to 5 ℃ to crystallize, the filtration is carried out, the filter cake is dried at 60 ℃ to obtain 90.6g of nalmefene hydrochloride monohydrate, and the mass yield is 87.2%.
Example 2
As shown in fig. 1, a process flow chart of a recovery and reuse method of the nalmefene hydrochloride mother liquor is shown, 118g of the nalmefene hydrochloride refined mother liquor (wherein the mass concentration of the nalmefene hydrochloride is about 20% and the solvent is water) is added into a reaction kettle, 400g of purified water is added, sodium carbonate solid is added, the pH is regulated to 8-9, and stirring is carried out for 30min; filtering to obtain nalmefene free alkali; adding 40g of nalmefene free base and absolute ethyl alcohol into a reaction bottle, heating and refluxing, and stirring for 0.5h; slowly cooling to 20 ℃, adding 14g of hydrochloric acid, and stirring for 5 hours; filtering, drying a filter cake at 60 ℃ to obtain 21.6g of mother liquor recovered nalmefene hydrochloride crude product;
100g of crude nalmefene hydrochloride and 21.6 mother liquor are combined to recover crude nalmefene hydrochloride, 120g of purified water is added, the temperature is raised to 80 ℃ for dissolving, the temperature is slowly lowered to 5 ℃ for crystallization, filtration and 60 ℃ drying of filter cakes are carried out, 107.7g of nalmefene hydrochloride monohydrate is obtained, the mass yield is 88.6%, and the recovery yield is about 19.1%.
Example 3
1122G of nalmefene hydrochloride refined mother liquor (the mass concentration of the nalmefene hydrochloride is about 21 percent, and the solvent is water) is added into a reaction kettle, 4L of purified water is added, sodium carbonate solid is added, the pH is regulated to 8-9, and stirring is carried out for 30min; filtering to obtain nalmefene free alkali; adding 400g of nalmefene free base and absolute ethyl alcohol into a reaction bottle, heating and refluxing, and stirring for 1h; slowly cooling to 20 ℃, adding 139g of hydrochloric acid, and stirring for 5 hours; filtering, drying the filter cake at 60 ℃ to obtain 217g of crude nalmefene hydrochloride recovered from the mother liquor.
1008G of crude nalmefene hydrochloride and 217g of mother liquor recovered crude nalmefene hydrochloride are combined, 1200g of purified water is added, the temperature is raised to 80 ℃ for dissolving, the temperature is slowly lowered to 5 ℃ for crystallization, filtration and 60 ℃ drying of filter cakes are carried out, 1097.6g of nalmefene hydrochloride monohydrate is obtained, the mass yield is 89.6%, and the recovery yield is 19.2%.
Example 4
1357G of nalmefene hydrochloride refined mother liquor (the mass concentration of the nalmefene hydrochloride is about 19%, the solvent is water, the purity of the nalmefene hydrochloride is 99.06% as shown in figure 3) is added into a reaction kettle, 4.5L of purified water is added, sodium carbonate solid is added, the pH is regulated to 8-9, and stirring is carried out for 30min; filtering to obtain nalmefene free alkali; adding 500g of nalmefene free base and absolute ethyl alcohol into a reaction bottle, heating and refluxing, and stirring for 1h; slowly cooling to 20 ℃, adding 152g of hydrochloric acid, and stirring for 5 hours; filtering, drying the filter cake at 60 ℃ to obtain mother liquor recovered nalmefene hydrochloride crude product 234g, wherein the HPLC chart is shown in figure 4, and the purity is 99.42%.
And (3) mixing 1032g of crude nalmefene hydrochloride with 234g of crude nalmefene hydrochloride recovered from mother liquor, adding 1300g of purified water, heating to 80 ℃ to dissolve, slowly cooling to 5 ℃ for crystallization, filtering, drying a filter cake at60 ℃ to obtain 1143.2g of nalmefene hydrochloride monohydrate, wherein the mass yield is 90.3%, the recovery yield is 20.5%, and the HPLC spectrum of the nalmefene hydrochloride monohydrate is shown in figure 5, and the purity is 99.91%.
The invention performs comparative analysis on the quality of the crude nalmefene hydrochloride product and the crude nalmefene hydrochloride product recovered from the mother liquor in the above examples, and the results are shown in the table:
By contrast, the mother liquor obtained after the refined mother liquor of nalmefene hydrochloride is recovered and purified is equivalent to the crude nalmefene hydrochloride without recovery, and the technological process of recovering and reusing the crude nalmefene hydrochloride is carried out firstly, so that the nalmefene hydrochloride monohydrate with single impurity less than 0.1% and purity more than 99.9% and meeting the pharmacopoeia quality standard can be prepared. Compared with the recovery process without mother liquor, the recovery method of the invention obviously improves the yield of nalmefene hydrochloride by about 20 percent and greatly reduces the material cost.
The above embodiments are merely for illustrating the technical ideas and features of the present invention, and are not meant to be exclusive or limiting. It will be understood by those skilled in the art that various changes may be made and equivalents may be substituted for elements thereof without departing from the scope of the invention.
Claims (5)
1. The method for recycling the nalmefene hydrochloride mother liquor is characterized by comprising the following steps:
Adding alkali into the refined nalmefene hydrochloride mother solution for dissociation, and filtering to obtain nalmefene free alkali; after recrystallization, hydrochloric acid salifying to obtain mother liquor for recovering nalmefene hydrochloride crude product;
And (3) combining the crude nalmefene hydrochloride recovered from the mother liquor with the crude nalmefene hydrochloride, carrying out purified hydrothermal dissolution, cooling crystallization, carrying out solid-liquid separation to obtain a filter cake and a filtrate, drying the filter cake to obtain white crystalline powder, namely the nalmefene hydrochloride monohydrate, wherein the filtrate is refined mother liquor containing the nalmefene hydrochloride.
2. The method for recycling and reusing nalmefene hydrochloride mother liquor according to claim 1, wherein the alkali adopted for adding alkali for dissociation is one or more of sodium bicarbonate, sodium carbonate, potassium carbonate, sodium hydroxide and potassium hydroxide.
3. The method for recycling and applying the nalmefene hydrochloride mother liquor according to claim 1, wherein the solvent for recrystallization is one or more of methanol, ethanol, isopropanol, acetone, methyl ethyl ketone and methyl isobutyl ketone.
4. The method for recycling and reusing nalmefene hydrochloride mother liquor according to claim 1, wherein the temperature of cooling crystallization is 0 ℃ to 30 ℃.
5. The method for recycling and reusing nalmefene hydrochloride mother liquor according to claim 1, wherein the temperature of drying the filter cake is 40-60 ℃.
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Citations (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4535157A (en) * | 1983-11-01 | 1985-08-13 | Key Pharmaceuticals, Inc. | Process for making 6-desoxy-6-methylenenaloxone and 6-desoxy-6-methylenenaltrexone |
| US4751307A (en) * | 1985-01-17 | 1988-06-14 | Mallinckrodt, Inc. | Wittig-reaction processes |
| SG176205A1 (en) * | 2009-05-25 | 2011-12-29 | Lundbeck & Co As H | Preparation of nalmefene hydrochloride from naltrexone |
| CN102325778A (en) * | 2008-12-05 | 2012-01-18 | H.隆德贝克有限公司 | Nalmefene hydrochloride dihydrate |
| CN102584840A (en) * | 2011-12-28 | 2012-07-18 | 南京优科生物医药有限公司 | Method for preparing nalmefene compound |
| CN103012416A (en) * | 2011-09-28 | 2013-04-03 | 辽宁海思科制药有限公司 | Method for preparing high-purity nalmefene hydrochloride |
| CN103204859A (en) * | 2013-04-25 | 2013-07-17 | 四川海思科制药有限公司 | Nalmefene hydrochloride compound and preparation method thereof |
| CN104093721A (en) * | 2011-12-06 | 2014-10-08 | H.隆德贝克有限公司 | Process for recovery of nalmefene hydrochloride |
| CN105646508A (en) * | 2016-02-17 | 2016-06-08 | 南京卓泰医药科技有限公司 | Preparation method of nalmefene hydrochloride monohydrate |
| CN106167492A (en) * | 2016-07-11 | 2016-11-30 | 西藏易明西雅医药科技股份有限公司 | A kind of purification process of nalmefene hydrochloride |
| JP2019031524A (en) * | 2008-12-05 | 2019-02-28 | ハー・ルンドベック・アクチエゼルスカベット | Nalmefene hydrochloride dihydrate |
-
2024
- 2024-04-02 CN CN202410390815.9A patent/CN117986261B/en active Active
Patent Citations (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4535157A (en) * | 1983-11-01 | 1985-08-13 | Key Pharmaceuticals, Inc. | Process for making 6-desoxy-6-methylenenaloxone and 6-desoxy-6-methylenenaltrexone |
| US4751307A (en) * | 1985-01-17 | 1988-06-14 | Mallinckrodt, Inc. | Wittig-reaction processes |
| CN102325778A (en) * | 2008-12-05 | 2012-01-18 | H.隆德贝克有限公司 | Nalmefene hydrochloride dihydrate |
| CN104211707A (en) * | 2008-12-05 | 2014-12-17 | H.隆德贝克有限公司 | Nalmefene hydrochloride dihydrate |
| JP2019031524A (en) * | 2008-12-05 | 2019-02-28 | ハー・ルンドベック・アクチエゼルスカベット | Nalmefene hydrochloride dihydrate |
| SG176205A1 (en) * | 2009-05-25 | 2011-12-29 | Lundbeck & Co As H | Preparation of nalmefene hydrochloride from naltrexone |
| CN103012416A (en) * | 2011-09-28 | 2013-04-03 | 辽宁海思科制药有限公司 | Method for preparing high-purity nalmefene hydrochloride |
| CN104093721A (en) * | 2011-12-06 | 2014-10-08 | H.隆德贝克有限公司 | Process for recovery of nalmefene hydrochloride |
| CN102584840A (en) * | 2011-12-28 | 2012-07-18 | 南京优科生物医药有限公司 | Method for preparing nalmefene compound |
| CN103204859A (en) * | 2013-04-25 | 2013-07-17 | 四川海思科制药有限公司 | Nalmefene hydrochloride compound and preparation method thereof |
| CN105646508A (en) * | 2016-02-17 | 2016-06-08 | 南京卓泰医药科技有限公司 | Preparation method of nalmefene hydrochloride monohydrate |
| CN106167492A (en) * | 2016-07-11 | 2016-11-30 | 西藏易明西雅医药科技股份有限公司 | A kind of purification process of nalmefene hydrochloride |
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