CN106588689A - Method for recycling atorvastatin intermediate M4 from crystallization mother liquor waste liquor - Google Patents
Method for recycling atorvastatin intermediate M4 from crystallization mother liquor waste liquor Download PDFInfo
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- CN106588689A CN106588689A CN201611162211.0A CN201611162211A CN106588689A CN 106588689 A CN106588689 A CN 106588689A CN 201611162211 A CN201611162211 A CN 201611162211A CN 106588689 A CN106588689 A CN 106588689A
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- waste liquid
- mother solution
- crystalline mother
- atorvastatin intermediate
- atorvastatin
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C231/00—Preparation of carboxylic acid amides
- C07C231/22—Separation; Purification; Stabilisation; Use of additives
- C07C231/24—Separation; Purification
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- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention provides a method for recycling an atorvastatin intermediate M4 from crystallization mother liquor waste liquor. The method comprises the following steps that 1, the crystallization mother liquor waste liquor is taken, a certain amount of dichloromethane and ethyl alcohol are added, and stirring is conducted; 2, a certain amount of potassium carbonate and kieselguhr are added, and stirring is conducted for hours; 3, centrifugation is conducted, waste residues are filtered out, a filtrate is concentrated, and a crude atorvastatin intermediate M4 product is obtained; 4, the crude product is subjected to water beating, suction filtration and drying, and the atorvastatin intermediate M4 with the content larger than 98.0% is obtained. Accordingly, the purpose of recycling the atorvastatin intermediate M4 from the crystallization mother liquor waste liquor is achieved, the technology is simple, the cost is low, the energy consumption is low, less needed equipment is needed, and discharge of the three wastes is reduced.
Description
Technical field
The invention belongs to the purification technique field of the chemical products three wastes, and in particular to return from crystalline mother solution waste liquid from one kind
The method for receiving atorvastatin intermediate M4.
Background technology
In atorvastatin intermediate M4 productions, crystalline mother solution waste liquid is secondary crystallization disposing mother liquor atorvastatin M4
Afterwards, after remaining feed liquid recycling design, the waste liquid of direct barrelling.During long-term storage, there is caking phenomenon, with the shape of waste liquid
Formula is more intractable, causes long-term accumulation, causes energy waste and environmental pollution.Domestic and international pertinent literature is consulted, to crystalline mother solution
The report of devil liquor recovery M4 does not almost have, not enough for more than, need exploitation it is a kind of it is not high to equipment requirements, simple to operate, into
This is low, save energy, beneficial to the method for environmentally friendly recovery atorvastatin M4.Crystalline mother solution waste liquid is mainly consisted of
M4（Account for the 25% of waste liquid quality）, methanol（Account for the 60% of waste liquid quality）, impurity mixture（Account for the 15% of waste liquid quality）Mixing
Thing.In order to reduce three waste discharge, the utilization rate of material in waste residue is improved, need to recycle crystalline mother solution waste liquid.
The content of the invention
It is an object of the invention to provide reclaiming the side of atorvastatin intermediate M4 from a kind of waste liquid from crystalline mother solution
Method.
Based on above-mentioned purpose, following technical scheme is this invention takes：
A kind of method that atorvastatin intermediate M4 is reclaimed in waste liquid from crystalline mother solution, comprises the steps：1）Take crystallization female
Liquid waste liquid, adds a certain amount of dichloromethane and alcohol mixed solvent, stirring；2）A certain amount of potassium carbonate and kieselguhr are added,
Stirring a few hours；3）Centrifugation, filters out waste residue, and filtrate is concentrated to give atorvastatin intermediate M4 crude products；4）Crude product is carried out
Water beating, sucking filtration, drying, obtain atorvastatin intermediate M4 of the content more than 98.0 ﹪.
The method that atorvastatin intermediate M4 is reclaimed in a kind of above-mentioned waste liquid from crystalline mother solution, it is characterised in that dichloro
Methane and alcohol mixed solvent and the mass ratio of crystalline mother solution waste liquid are 5 ~ 10:1, the mass ratio of wherein dichloromethane and ethanol is
2:1。
The method that atorvastatin intermediate M4 is reclaimed in a kind of above-mentioned waste liquid from crystalline mother solution, it is characterised in that add
Potassium carbonate and kieselguhr, stir 2～5 hours, and the mass ratio of potassium carbonate and crystalline mother solution waste liquid is 0.10 ~ 0.25:1, kieselguhr
It is 0.01 ~ 0.03 with the mass ratio of crystalline mother solution waste liquid:1.
The method that atorvastatin intermediate M4 is reclaimed in a kind of above-mentioned waste liquid from crystalline mother solution, when crude product is beaten, water
In crude product mass ratio be 5～10：1.
By above technical scheme, the final atorvastatin intermediate M4 contents for reclaiming up to more than 98%, moisture Control
Below 0.10%, through refined, product market quality standard is reached.Present invention process is simple, and with low cost, energy consumption is low, required
Equipment is few, realizes from crystalline mother solution waste liquid to the recycling of atorvastatin intermediate M4, reduces the discharge of the three wastes, profit
In industrialization.
Specific embodiment
Technical scheme is described in further detail below by way of specific embodiment, but the protection model of the present invention
Enclose and be not limited thereto.
Embodiment 1
A kind of method that atorvastatin intermediate M4 is reclaimed in the waste liquid from crystalline mother solution
Comprise the following steps that：
Atorvastatin intermediate M4 crystalline mother solution waste liquid 540kg are added in 5000L reactors（135kg containing M4, methanol
324kg, impurity 81kg）, add 1080kg dichloromethane and 540kg ethanol.35～40 DEG C are heated to, are stirred 0.5 hour,
It is completely dissolved, 0～10 DEG C is then cooled to.135kg potassium carbonate and 10.8kg kieselguhr are added, after stirring 2～3 hours,
Filter, a small amount of dichloromethane of filter cake.After filtrate reduced in volume recycling design, after stirring is cooled to 10～20 DEG C, insulation
After crystallization 1 hour, centrifugation, filtrate collection send water treatment station, filter cake about 125kg to put into 650kg water, be stirred at room temperature 2 hours.Material
Liquid is put to centrifuge and gets rid of material to dry, and filter cake is placed in double-cone vacuum dryer and is vacuum dried, 50 ± 5 DEG C of temperature, vacuum less than-
0.080Mpa, is dried 7 hours, obtains 121kg products, the response rate 89.6%.
Embodiment 2
A kind of method that atorvastatin intermediate M4 is reclaimed in the waste liquid from crystalline mother solution
Comprise the following steps that：
The high waste liquid 540kg of atorvastatin intermediate M4 crystalline mother solutions is added in 5000L reactors（135kg containing M4, methanol
324kg, impurity 81kg）, add 1620kg dichloromethane and 540kg ethanol to be warming up to 35～40 DEG C, stir 0.5 hour so as to
It is completely dissolved, is then cooled to 0～10 DEG C, add 135kg potassium carbonate and 10.8kg kieselguhr, after stirring 2～3 hours, filters,
The a small amount of dichloromethane of filter cake, after filtrate reduced in volume recycling design, after stirring is cooled to 10～20 DEG C, insulation crystallization 1
After hour, centrifugation, filtrate collection send water treatment station, filter cake 122kg in 750 water of input, to be stirred at room temperature 2 hours.Feed liquid put to from
Scheming gets rid of material to dry, and filter cake is placed in double-cone vacuum dryer and is vacuum dried, 50 ± 5 DEG C of temperature, vacuum less than-
0.080Mpa, is dried 7 hours, obtains 119kg products, the response rate 88.1%.
Embodiment 3
A kind of method that atorvastatin intermediate M4 is reclaimed in the waste liquid from crystalline mother solution
Comprise the following steps that：
Atorvastatin intermediate M4 crystalline mother solution waste liquid 540kg are added in 5000L reactors（135kg containing M4, methanol
324kg, impurity 81kg）, add 1080kg dichloromethane and 540kg ethanol to be warming up to 35～40 DEG C, stir 0.5 hour so as to
It is completely dissolved, is then cooled to 0～10 DEG C, add 135kg potassium carbonate and 10.8kg kieselguhr, after stirring 2～3 hours, filters,
The a small amount of dichloromethane of filter cake, after filtrate reduced in volume recycling design, after stirring is cooled to 10～20 DEG C, insulation crystallization 1
After hour, centrifugation, filtrate collection send water treatment station, filter cake about 125kg to put into 750kg water, be stirred at room temperature 2 hours.Feed liquid put to
Centrifuge gets rid of material to dry, and filter cake is placed in double-cone vacuum dryer and is vacuum dried, 50 ± 5 DEG C of temperature, vacuum less than-
0.080MPa is dried 7 hours, obtains 120kg products, the response rate 88.9%.
Claims (4)
1. the present invention provides a kind of method that atorvastatin intermediate M4 is reclaimed in waste liquid from crystalline mother solution, including following step
Suddenly：1）Crystalline mother solution waste liquid is taken, a certain amount of dichloromethane and alcohol mixed solvent, stirring is added；2）Add a certain amount of carbon
Sour potassium and kieselguhr, stir a few hours；3）Centrifugation, filters out waste residue, and filtrate is concentrated to give atorvastatin intermediate M4 crude products；
4）Enter water-filling beating, sucking filtration, drying to crude product, obtain atorvastatin intermediate M4 of the content more than 98.0 ﹪.
2. the method that atorvastatin intermediate M4 is reclaimed in a kind of waste liquid from crystalline mother solution according to claim 1, its
It is characterised by that dichloromethane and alcohol mixed solvent are 5 ~ 10 with the mass ratio of crystalline mother solution waste liquid:1, wherein dichloromethane and second
The mass ratio of alcohol is 2:1.
3. the method that atorvastatin intermediate M4 is reclaimed in a kind of waste liquid from crystalline mother solution according to claim 1, its
It is characterised by adding potassium carbonate and kieselguhr, stirs 2～5 hours, the mass ratio of potassium carbonate and crystalline mother solution waste liquid is 0.10 ~
0.25:1, kieselguhr is 0.01 ~ 0.03 with the mass ratio of crystalline mother solution waste liquid:1.
4. the method that atorvastatin intermediate M4 is reclaimed in a kind of waste liquid from crystalline mother solution according to claim 1, slightly
When product are beaten, water is 5～10 in the mass ratio of crude product：1.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201611162211.0A CN106588689A (en) | 2016-12-15 | 2016-12-15 | Method for recycling atorvastatin intermediate M4 from crystallization mother liquor waste liquor |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201611162211.0A CN106588689A (en) | 2016-12-15 | 2016-12-15 | Method for recycling atorvastatin intermediate M4 from crystallization mother liquor waste liquor |
Publications (1)
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| CN106588689A true CN106588689A (en) | 2017-04-26 |
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| CN201611162211.0A Pending CN106588689A (en) | 2016-12-15 | 2016-12-15 | Method for recycling atorvastatin intermediate M4 from crystallization mother liquor waste liquor |
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Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1223647A (en) * | 1996-07-29 | 1999-07-21 | 沃尼尔·朗伯公司 | Improved process for the synthesis of protected esters of (S)-3,4-dihydroxytubyric acid |
| WO2003004457A2 (en) * | 2001-07-04 | 2003-01-16 | Ciba Specialty Chemicals Holding Inc. | Preparation process for atorvastatin and intermediates |
| CN102382006A (en) * | 2011-11-11 | 2012-03-21 | 连云港宏业化工有限公司 | Synthesis method of 2-[2-(4-fluorophenyl)-2-oxa-1-phenylethyl]-4-methyl-3-oxa-N-phenylpentanamide |
| WO2012143933A1 (en) * | 2011-04-21 | 2012-10-26 | Vijayasri Organics Limited | A PROCESS FOR PREPARATION OF 4-FLUORO-α-[2-METHYL-L-OXOPROPYL]-γ-OXO-N-β-DIPHENYLBENZENE BUTANE AMIDE |
| WO2012145808A1 (en) * | 2011-04-25 | 2012-11-01 | Universidade Estadual De Campinas - Unicamp | Method for preparing atorvastatin calcium using new intermediates and resulting atorvastatin |
-
2016
- 2016-12-15 CN CN201611162211.0A patent/CN106588689A/en active Pending
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1223647A (en) * | 1996-07-29 | 1999-07-21 | 沃尼尔·朗伯公司 | Improved process for the synthesis of protected esters of (S)-3,4-dihydroxytubyric acid |
| WO2003004457A2 (en) * | 2001-07-04 | 2003-01-16 | Ciba Specialty Chemicals Holding Inc. | Preparation process for atorvastatin and intermediates |
| WO2012143933A1 (en) * | 2011-04-21 | 2012-10-26 | Vijayasri Organics Limited | A PROCESS FOR PREPARATION OF 4-FLUORO-α-[2-METHYL-L-OXOPROPYL]-γ-OXO-N-β-DIPHENYLBENZENE BUTANE AMIDE |
| WO2012145808A1 (en) * | 2011-04-25 | 2012-11-01 | Universidade Estadual De Campinas - Unicamp | Method for preparing atorvastatin calcium using new intermediates and resulting atorvastatin |
| CN102382006A (en) * | 2011-11-11 | 2012-03-21 | 连云港宏业化工有限公司 | Synthesis method of 2-[2-(4-fluorophenyl)-2-oxa-1-phenylethyl]-4-methyl-3-oxa-N-phenylpentanamide |
Non-Patent Citations (2)
| Title |
|---|
| MAHESH REDDY GHANTA等: "An Efficient Synthesis of Highly Substituted Pyrrole and Bis Pyrrole Derivatives", 《J. HETEROCYCLIC CHEM.》 * |
| 范朋高等: "4-氟-α-(2-甲基-1-氧丙基)-γ-氧-N , β-二苯基-苯丁酰胺的合成", 《中国药物化学杂志》 * |
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Application publication date: 20170426 |