CN115572227A - Method for preparing carbasalate calcium - Google Patents
Method for preparing carbasalate calcium Download PDFInfo
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- CN115572227A CN115572227A CN202211261300.6A CN202211261300A CN115572227A CN 115572227 A CN115572227 A CN 115572227A CN 202211261300 A CN202211261300 A CN 202211261300A CN 115572227 A CN115572227 A CN 115572227A
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- Prior art keywords
- calcium
- aspirin
- urea
- solvent
- certain embodiments
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- 238000000034 method Methods 0.000 title claims abstract description 21
- 229960004105 carbasalate calcium Drugs 0.000 title claims abstract description 17
- VYMUGTALCSPLDM-UHFFFAOYSA-L carbasalate calcium Chemical compound [Ca+2].NC(N)=O.CC(=O)OC1=CC=CC=C1C([O-])=O.CC(=O)OC1=CC=CC=C1C([O-])=O VYMUGTALCSPLDM-UHFFFAOYSA-L 0.000 title claims abstract description 17
- BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 claims abstract description 39
- 229960001138 acetylsalicylic acid Drugs 0.000 claims abstract description 39
- 239000004202 carbamide Substances 0.000 claims abstract description 26
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 claims abstract description 25
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims abstract description 22
- 239000002904 solvent Substances 0.000 claims abstract description 17
- AXCZMVOFGPJBDE-UHFFFAOYSA-L calcium dihydroxide Chemical compound [OH-].[OH-].[Ca+2] AXCZMVOFGPJBDE-UHFFFAOYSA-L 0.000 claims abstract description 16
- 239000000920 calcium hydroxide Substances 0.000 claims abstract description 16
- 229910001861 calcium hydroxide Inorganic materials 0.000 claims abstract description 16
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 claims abstract description 15
- 229910052791 calcium Inorganic materials 0.000 claims abstract description 15
- 239000011575 calcium Substances 0.000 claims abstract description 15
- BRPQOXSCLDDYGP-UHFFFAOYSA-N calcium oxide Chemical compound [O-2].[Ca+2] BRPQOXSCLDDYGP-UHFFFAOYSA-N 0.000 claims abstract description 12
- 239000000292 calcium oxide Substances 0.000 claims abstract description 12
- ODINCKMPIJJUCX-UHFFFAOYSA-N calcium oxide Inorganic materials [Ca]=O ODINCKMPIJJUCX-UHFFFAOYSA-N 0.000 claims abstract description 12
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 51
- 239000012065 filter cake Substances 0.000 claims description 11
- 238000001035 drying Methods 0.000 claims description 10
- 239000000047 product Substances 0.000 claims description 8
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 6
- 238000004519 manufacturing process Methods 0.000 claims description 5
- 230000035484 reaction time Effects 0.000 claims description 5
- 238000001914 filtration Methods 0.000 claims description 4
- YZBQHRLRFGPBSL-RXMQYKEDSA-N carbapenem Chemical compound C1C=CN2C(=O)C[C@H]21 YZBQHRLRFGPBSL-RXMQYKEDSA-N 0.000 claims 1
- 239000002253 acid Substances 0.000 abstract description 5
- 239000011230 binding agent Substances 0.000 abstract description 5
- 239000002994 raw material Substances 0.000 abstract 1
- 239000000243 solution Substances 0.000 description 8
- 238000000967 suction filtration Methods 0.000 description 7
- 239000000843 powder Substances 0.000 description 6
- 239000000706 filtrate Substances 0.000 description 5
- 238000002360 preparation method Methods 0.000 description 5
- 238000003756 stirring Methods 0.000 description 5
- 239000002699 waste material Substances 0.000 description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 5
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 4
- 238000009776 industrial production Methods 0.000 description 4
- 239000007787 solid Substances 0.000 description 4
- 239000000725 suspension Substances 0.000 description 4
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 230000008901 benefit Effects 0.000 description 3
- 238000002425 crystallisation Methods 0.000 description 3
- 230000008025 crystallization Effects 0.000 description 3
- 238000005516 engineering process Methods 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- PAWQVTBBRAZDMG-UHFFFAOYSA-N 2-(3-bromo-2-fluorophenyl)acetic acid Chemical compound OC(=O)CC1=CC=CC(Br)=C1F PAWQVTBBRAZDMG-UHFFFAOYSA-N 0.000 description 2
- MBNMSERYORMPIB-UHFFFAOYSA-N 2-acetyloxybenzoic acid;calcium Chemical compound [Ca].CC(=O)OC1=CC=CC=C1C(O)=O MBNMSERYORMPIB-UHFFFAOYSA-N 0.000 description 2
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 2
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- 229940035676 analgesics Drugs 0.000 description 2
- 229910000019 calcium carbonate Inorganic materials 0.000 description 2
- KRALOLGXHLZTCW-UHFFFAOYSA-L calcium;2-acetyloxybenzoate Chemical compound [Ca+2].CC(=O)OC1=CC=CC=C1C([O-])=O.CC(=O)OC1=CC=CC=C1C([O-])=O KRALOLGXHLZTCW-UHFFFAOYSA-L 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 238000010907 mechanical stirring Methods 0.000 description 2
- 238000012805 post-processing Methods 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- XNWFRZJHXBZDAG-UHFFFAOYSA-N 2-METHOXYETHANOL Chemical compound COCCO XNWFRZJHXBZDAG-UHFFFAOYSA-N 0.000 description 1
- LWUQBSVJOMGTOY-UHFFFAOYSA-N 2-acetyloxybenzoic acid;calcium;urea Chemical compound [Ca].NC(N)=O.CC(=O)OC1=CC=CC=C1C(O)=O LWUQBSVJOMGTOY-UHFFFAOYSA-N 0.000 description 1
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 241000287828 Gallus gallus Species 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 206010037660 Pyrexia Diseases 0.000 description 1
- 208000007271 Substance Withdrawal Syndrome Diseases 0.000 description 1
- 241000282887 Suidae Species 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- 235000019270 ammonium chloride Nutrition 0.000 description 1
- 235000011114 ammonium hydroxide Nutrition 0.000 description 1
- 239000000730 antalgic agent Substances 0.000 description 1
- 230000001754 anti-pyretic effect Effects 0.000 description 1
- 239000002221 antipyretic Substances 0.000 description 1
- 239000003907 antipyretic analgesic agent Substances 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 239000007900 aqueous suspension Substances 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 239000001110 calcium chloride Substances 0.000 description 1
- 229910001628 calcium chloride Inorganic materials 0.000 description 1
- ZCCIPPOKBCJFDN-UHFFFAOYSA-N calcium nitrate Inorganic materials [Ca+2].[O-][N+]([O-])=O.[O-][N+]([O-])=O ZCCIPPOKBCJFDN-UHFFFAOYSA-N 0.000 description 1
- 239000001569 carbon dioxide Substances 0.000 description 1
- 229910002092 carbon dioxide Inorganic materials 0.000 description 1
- 238000012822 chemical development Methods 0.000 description 1
- 235000013330 chicken meat Nutrition 0.000 description 1
- 239000003651 drinking water Substances 0.000 description 1
- 235000020188 drinking water Nutrition 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000002360 explosive Substances 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 229910017053 inorganic salt Inorganic materials 0.000 description 1
- 239000012046 mixed solvent Substances 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 239000002547 new drug Substances 0.000 description 1
- 239000000820 nonprescription drug Substances 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 238000001694 spray drying Methods 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- ILWRPSCZWQJDMK-UHFFFAOYSA-N triethylazanium;chloride Chemical compound Cl.CCN(CC)CC ILWRPSCZWQJDMK-UHFFFAOYSA-N 0.000 description 1
- 239000000273 veterinary drug Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C67/00—Preparation of carboxylic acid esters
- C07C67/28—Preparation of carboxylic acid esters by modifying the hydroxylic moiety of the ester, such modification not being an introduction of an ester group
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C273/00—Preparation of urea or its derivatives, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups
- C07C273/02—Preparation of urea or its derivatives, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups of urea, its salts, complexes or addition compounds
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C273/00—Preparation of urea or its derivatives, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups
- C07C273/02—Preparation of urea or its derivatives, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups of urea, its salts, complexes or addition compounds
- C07C273/14—Separation; Purification; Stabilisation; Use of additives
- C07C273/16—Separation; Purification
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention relates to a method for preparing carbasalate calcium by using alcohol as a solvent, using aspirin and urea as raw materials, and using calcium oxide or calcium hydroxide as a calcium source and an acid-binding agent simultaneously.
Description
Technical Field
The invention relates to the field of medicinal chemistry, in particular to a preparation method of an antipyretic analgesic drug, and specifically relates to a preparation method of a veterinary drug, namely carbasalate calcium.
Background
The carbasalate calcium is also called acetylsalicylic acid calcium urea or aspirin calcium urea, is a complex of acetylsalicylic acid calcium and urea, and is chemically named as bis- (2-acetoxybenzoic acid calcium) urea. The carbasalate calcium has good water solubility, is fast to be absorbed by oral administration, and has the functions of relieving fever, easing pain and resisting inflammation. The carbasalate calcium is loaded in European pharmacopoeia, is listed as an over-the-counter drug in the United states, belongs to three new drugs in China, and is the only one group of antipyretic analgesics approved by Ministry of agriculture in China for edible animals such as pigs, chickens and cattle. The carbasalate calcium can be used for drinking water and mixing materials, has no residue in animal bodies, does not need a drug withdrawal period, and has wide market prospect.
In the prior art CN 101575305A, methanol or ethanol is used as a single solvent, aspirin, calcium nitrate, urea and the like are stirred and dissolved, then an ammonia alcohol solution is introduced for crystallization until the reaction end point, and the mixture is centrifuged and dried, so that the yield is 95-96%. Although the method overcomes the problems of poor safety, high cost and difficult solvent recovery caused by using a mixed solvent of ethylene glycol monomethyl ether and ethanol, the method can not avoid the generation of a large amount of by-product ammonium nitrate, and the ammonium nitrate is an explosive product, so that great potential safety hazard exists when the generated waste liquid is treated.
In the prior art CN 114315574A, ethanol/water is used as a solvent, aspirin, calcium chloride and urea are stirred and dissolved, triethylamine is added dropwise at a temperature controlled by a DSC system, the temperature is reduced after the reaction is finished, crystallization is carried out, suction filtration is carried out, a filter cake is rinsed by ethanol, and drying is carried out, thus obtaining the carbasalate calcium, and the yield is about 94%. The filtrate obtained by the method is concentrated and recycled with ethanol, so that the use cost and the production cost of the solvent are reduced, but more triethylamine hydrochloric acid waste residues are generated. Other reports use similar process to synthesize ammonia gas or ammonia water as acid-binding agent, but the ammonium chloride waste liquid or waste residue will be generated finally.
In the prior art CN 102382013A, water is used as a solvent, aspirin and urea are added and stirred, calcium carbonate is added in batches, stirring is continued for a period of time after the addition, insoluble substances are removed by filtration, methanol is added into filtrate for crystallization, the filtrate is filtered, a filter cake is soaked and washed by methanol, the filtrate is filtered and dried, and the product yield can reach 94%. The method takes calcium carbonate as a calcium source and an acid-binding agent, reduces the cost, does not produce inorganic salt waste residues, but produces carbon dioxide gas, and is not beneficial to industrial production.
In the prior art CN 106496074A, aspirin and urea are firstly added into water and stirred to be dissolved, then the mixture is dripped into calcium hydroxide/water suspension, after the reaction is finished, the mixture is filtered, and the filtrate is spray-dried to obtain the product, wherein the yield is about 95%. The method takes the calcium hydroxide as a calcium source and an acid-binding agent simultaneously, is safe and environment-friendly, but the spray drying equipment is expensive, so that the investment is huge at the early stage of production.
Therefore, the method has important practical value by improving the existing preparation process of the carbasalate calcium.
Disclosure of Invention
Problems to be solved by the invention
In order to solve the problems in the prior art, the invention provides the preparation method of the carbasalate calcium, which is simple and convenient to operate, good in economy, friendly to reaction equipment and suitable for industrial production.
Means for solving the problems
The invention provides a method for preparing carbasalate calcium, which comprises the following steps:
step S: aspirin, a calcium source and urea react in a solvent 1 to obtain carbasalate calcium;
the calcium source is selected from one or more of calcium oxide and calcium hydroxide;
the solvent 1 is selected from one or more of methanol, ethanol and isopropanol.
Preferably, the mass ratio of aspirin to urea in step S is 1.
Preferably, the mass ratio of aspirin to calcium oxide in step S is 1.
Preferably, the mass ratio of aspirin to calcium hydroxide in step S is 1.
Preferably, the mass volume ratio of aspirin to solvent 1 in step S is 1; the unit is g/mL.
Preferably, the reaction temperature of step S is 0-50 deg.C, preferably 20-40 deg.C.
Preferably, the reaction time of step S is 1 to 10 hours, preferably 4 to 5 hours.
Preferably, the post-processing step of step S includes: and after the reaction is finished, filtering, and drying a filter cake to obtain a product.
ADVANTAGEOUS EFFECTS OF INVENTION
The method takes calcium oxide or calcium hydroxide as a calcium source and an acid-binding agent simultaneously to synthesize the carbasalate calcium, only produces products and water, is safe and environment-friendly, has simple and convenient process, low cost and good economic benefit, and has better guiding significance for realizing industrial production. Meanwhile, the preparation method has high reaction yield, and the obtained product has high purity, and is suitable for industrial production.
Detailed Description
In order to make the technical solution and advantages of the present invention more comprehensible, a detailed description is given below by way of specific examples. Unless defined otherwise, technical and scientific terms used herein have the same meaning as technical and scientific terms used in the technical field to which this application belongs.
The invention provides a method for preparing carbasalate calcium, which comprises the following steps:
step S: aspirin, a calcium source and urea react in a solvent 1 to obtain carbasalate calcium;
the calcium source is selected from one or more of calcium oxide and calcium hydroxide;
the solvent 1 is selected from one or more of methanol, ethanol and isopropanol.
In certain embodiments, the mass ratio of aspirin to urea in step S is 1.
In certain embodiments, the mass ratio of aspirin to urea in step S is 1.2 to 0.3.
In certain embodiments, the mass ratio of aspirin to urea in step S is 1.
In certain embodiments, the mass ratio of aspirin to calcium oxide in step S is 1.
In certain embodiments, the mass ratio of aspirin to calcium oxide in step S is 1.
In certain embodiments, the mass ratio of aspirin to calcium oxide in step S is 1.
In certain embodiments, the mass ratio of aspirin to calcium hydroxide in step S is 1.
In certain embodiments, the mass ratio of aspirin to calcium hydroxide in step S is 1.
In certain embodiments, the mass ratio of aspirin to calcium hydroxide in step S is 1.
In certain embodiments, the mass to volume ratio of aspirin to solvent 1 in step S is 1.
In certain embodiments, the mass to volume ratio of aspirin to solvent 1 in step S is 1.
In certain embodiments, the mass-to-volume ratio of aspirin to solvent 1 in step S is 1.
In certain embodiments, the reaction temperature of step S is from 0 to 50 ℃.
In certain embodiments, the reaction temperature of step S is from 20 to 40 ℃.
In certain embodiments, the step S reaction temperature is 20 ℃, 21 ℃, 22 ℃, 23 ℃, 24 ℃, 25 ℃, 26 ℃, 27 ℃, 28 ℃, 29 ℃, 30 ℃, 31 ℃, 32 ℃, 33 ℃, 34 ℃, 35 ℃, 36 ℃, 37 ℃, 38 ℃, 39 ℃, 40 ℃.
In certain embodiments, the reaction time of step S is 1 to 10 hours.
In certain embodiments, the reaction time of step S is 4 to 5 hours.
In certain embodiments, the reaction time of step S is 4.0 hours, 4.5 hours, 5.0 hours.
In certain embodiments, the reaction is carried out in a batch or dropwise manner.
In certain embodiments, the order of addition may be selected such that the aspirin solid is added in portions to the suspension of the calcium source and urea.
In certain embodiments, the dosing sequence optionally adds aspirin alcohol solution droplets to the suspension of the calcium source and urea.
In certain embodiments, the order of addition may optionally be to add the calcium source in portions to the solution of aspirin and urea.
In certain embodiments, the dosing sequence optionally adds the calcium source suspension dropwise to the solution of aspirin and urea.
In certain embodiments, the post-processing step of step S comprises: and after the reaction is finished, filtering, and drying a filter cake to obtain a product.
The method of the present invention is illustrated below by means of specific examples, which are to be understood as being illustrative of the basic principles, main features and advantages of the present invention, and the present invention is not limited in scope by the following examples; the implementation conditions used in the examples can be further adjusted according to specific requirements, and the implementation conditions not noted are generally those in routine experiments.
In the following examples, unless otherwise indicated, all temperatures are in degrees celsius and unless otherwise indicated, the various starting materials and reagents are commercially available or synthesized according to known methods, and none of the commercially available materials and reagents are used without further purification and unless otherwise indicated, commercially available manufacturers include, but are not limited to, the national drug group, the welfare technology limited, the schehia (shanghai) chemical development limited, the shanghai bibi medical technology limited, the shanghai meihel chemical technology limited, and the like.
In the examples, the solution in the reaction is an aqueous solution unless otherwise specified.
In the examples, the reaction temperature is, unless otherwise specified, from 20 ℃ to 30 ℃ at room temperature.
Example 1
Adding 310ml of methanol, 8.6g of calcium oxide and 13g of urea into a 500ml three-neck bottle, mechanically stirring for 5 minutes, adding 50g of solid aspirin in 4-5 batches, completing the addition for about 1 hour, and then controlling the temperature to be 30-40 ℃ to react for 5 hours; suction filtration, filter cake drying, white powder 60.2g, yield: 94.6 percent, content: 98 percent.
Example 2
50g of aspirin is weighed in a 500ml beaker, and 150ml of methanol is added to be stirred and dissolved for later use; 150ml of methanol, 8.5g of calcium oxide and 8.5g of urea are added into a 500ml three-mouth bottle, the mechanical stirring is carried out, then the aspirin methanol solution is dripped, the addition is finished within about 1 hour, and then the temperature is controlled to be 20-30 ℃ for reaction for 4 hours; suction filtration and filter cake drying gave 59.3g of white powder, yield: 93.2%, content: 98.2 percent.
Example 3
Adding 320ml of methanol, 12.9g of calcium hydroxide and 12g of urea into a 500ml three-neck bottle, mechanically stirring for 5 minutes, adding 50g of solid aspirin in 4-5 batches, finishing the addition within about 1 hour, and controlling the temperature to be 22-31 ℃ to react for 5 hours; suction filtration, filter cake drying, white powder 60.7g, yield: 95.4%, content: 99 percent.
Example 4
50g of aspirin is weighed in a 500ml beaker, and 150ml of methanol is added to be stirred and dissolved for later use; 150ml of methanol, 13.2g of calcium hydroxide and 15g of urea are added into a 500ml three-mouth bottle, the mechanical stirring is carried out for 5 minutes, then the aspirin methanol solution is dropwise added for about 1 hour, and then the temperature is controlled to be 20-30 ℃ for reaction for 4.5 hours; suction filtration and filter cake drying gave 61.1g of white powder, yield: 96 percent, content: 98.3 percent.
Example 5
Adding 350ml of methanol, 50g of aspirin and 15g of urea into a 500ml three-neck bottle, mechanically stirring for dissolving, adding 12.4g of solid calcium hydroxide in 5-6 batches in batches, completing the addition within about 1 hour, and then controlling the temperature to be 20-30 ℃ for reaction for 5 hours; suction filtration, filter cake drying, white powder 60g, yield: 94.3 percent, content: 99.1 percent.
Example 6
Adding 200ml of methanol, 50g of aspirin and 15g of urea into a 500ml three-neck flask, mechanically stirring for dissolving, dropwise adding a methanol suspension (12.5 g/100 ml) of calcium hydroxide for about 1 hour, and then controlling the temperature to be 23-32 ℃ for reaction for 5 hours; suction filtration and filter cake drying gave 59.4g of white powder, yield: 93.3%, content: 99.6 percent.
It should be understood that the above embodiments are exemplary and are not intended to encompass all possible implementations encompassed by the claims. Various modifications and changes may also be made on the basis of the above embodiments without departing from the scope of the present disclosure. Likewise, various features of the above embodiments may also be combined in any combination to form additional embodiments of the invention that may not be explicitly described. Therefore, the above examples only represent some embodiments of the present invention, and do not limit the scope of the present invention.
Claims (8)
1. A process for preparing carbapenem calcium, which comprises the steps of:
step S: aspirin, a calcium source and urea react in a solvent 1 to obtain carbasalate calcium;
the calcium source is selected from one or more of calcium oxide and calcium hydroxide;
the solvent 1 is selected from one or more of methanol, ethanol and isopropanol.
2. The process according to claim 1, wherein the mass ratio of aspirin to urea in step S is 1.
3. The production method according to any one of claims 1 to 2, wherein the mass ratio of aspirin to calcium oxide in step S is 1.
4. The production method according to any one of claims 1 to 3, wherein the mass ratio of aspirin to calcium hydroxide in step S is 1.
5. The process according to any one of claims 1 to 4, wherein the mass-to-volume ratio of aspirin to solvent 1 in step S is 1; the unit is g/mL.
6. The process according to any one of claims 1 to 5, wherein the reaction temperature in step S is from 0 ℃ to 50 ℃, preferably from 20 ℃ to 40 ℃.
7. The process according to any one of claims 1 to 6, wherein the reaction time of step S is from 1 to 10 hours, preferably from 4 to 5 hours.
8. The method of any one of claims 1 to 7, wherein the post-treatment step of step S comprises: after the reaction is finished, filtering, and drying a filter cake to obtain a product.
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| CN202211261300.6A CN115572227A (en) | 2022-10-14 | 2022-10-14 | Method for preparing carbasalate calcium |
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| CN202211261300.6A CN115572227A (en) | 2022-10-14 | 2022-10-14 | Method for preparing carbasalate calcium |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106496074A (en) * | 2016-08-31 | 2017-03-15 | 河北远征禾木药业有限公司 | A kind of preparation method of carbasalate calcium |
| CN107344919A (en) * | 2017-05-27 | 2017-11-14 | 山东久隆恒信药业有限公司 | A kind of preparation method of carbasalate calcium |
| CN109134315A (en) * | 2017-06-19 | 2019-01-04 | 河南后羿制药有限公司 | A kind of preparation method of carbasalate calcium and carbasalate calcium prepared by this method |
| CN110724057A (en) * | 2019-12-05 | 2020-01-24 | 山东省化工研究院 | Preparation method of carbasalate calcium |
-
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- 2022-10-14 CN CN202211261300.6A patent/CN115572227A/en active Pending
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106496074A (en) * | 2016-08-31 | 2017-03-15 | 河北远征禾木药业有限公司 | A kind of preparation method of carbasalate calcium |
| CN107344919A (en) * | 2017-05-27 | 2017-11-14 | 山东久隆恒信药业有限公司 | A kind of preparation method of carbasalate calcium |
| CN109134315A (en) * | 2017-06-19 | 2019-01-04 | 河南后羿制药有限公司 | A kind of preparation method of carbasalate calcium and carbasalate calcium prepared by this method |
| CN110724057A (en) * | 2019-12-05 | 2020-01-24 | 山东省化工研究院 | Preparation method of carbasalate calcium |
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