CN108484484A - The preparation method of 2- oxygen-ethyl nipecotate - Google Patents
The preparation method of 2- oxygen-ethyl nipecotate Download PDFInfo
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- CN108484484A CN108484484A CN201810497214.2A CN201810497214A CN108484484A CN 108484484 A CN108484484 A CN 108484484A CN 201810497214 A CN201810497214 A CN 201810497214A CN 108484484 A CN108484484 A CN 108484484A
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- Prior art keywords
- oxygen
- preparation
- diethyl malonate
- ethyl
- ethyl nipecotate
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- 238000002360 preparation method Methods 0.000 title claims abstract description 16
- 238000006243 chemical reaction Methods 0.000 claims abstract description 31
- LTMRRSWNXVJMBA-UHFFFAOYSA-L 2,2-diethylpropanedioate Chemical compound CCC(CC)(C([O-])=O)C([O-])=O LTMRRSWNXVJMBA-UHFFFAOYSA-L 0.000 claims abstract description 15
- NLHHRLWOUZZQLW-UHFFFAOYSA-N Acrylonitrile Chemical compound C=CC#N NLHHRLWOUZZQLW-UHFFFAOYSA-N 0.000 claims abstract description 15
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 14
- -1 2 cyanoethyl diethyl malonates Chemical class 0.000 claims abstract description 10
- 239000003054 catalyst Substances 0.000 claims abstract description 9
- 239000003426 co-catalyst Substances 0.000 claims abstract description 8
- 239000003960 organic solvent Substances 0.000 claims abstract description 7
- 238000002156 mixing Methods 0.000 claims abstract description 3
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 15
- 229910052739 hydrogen Inorganic materials 0.000 claims description 13
- 239000001257 hydrogen Substances 0.000 claims description 13
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 10
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 claims description 8
- RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 7
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-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
- 235000019441 ethanol Nutrition 0.000 claims description 5
- 239000002904 solvent Substances 0.000 claims description 5
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims description 4
- 239000003208 petroleum Substances 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
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 claims description 4
- 125000001731 2-cyanoethyl group Chemical group [H]C([H])(*)C([H])([H])C#N 0.000 claims description 3
- 238000001953 recrystallisation Methods 0.000 claims description 3
- LCGLNKUTAGEVQW-UHFFFAOYSA-N Dimethyl ether Chemical group COC LCGLNKUTAGEVQW-UHFFFAOYSA-N 0.000 claims description 2
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 claims description 2
- 229910000027 potassium carbonate Inorganic materials 0.000 claims description 2
- 229910000029 sodium carbonate Inorganic materials 0.000 claims description 2
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 claims description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims 3
- 239000003795 chemical substances by application Substances 0.000 claims 2
- 238000005815 base catalysis Methods 0.000 claims 1
- 229910017052 cobalt Inorganic materials 0.000 claims 1
- 239000010941 cobalt Substances 0.000 claims 1
- GUTLYIVDDKVIGB-UHFFFAOYSA-N cobalt atom Chemical compound [Co] GUTLYIVDDKVIGB-UHFFFAOYSA-N 0.000 claims 1
- 150000002148 esters Chemical class 0.000 claims 1
- 238000000034 method Methods 0.000 abstract description 8
- 238000004519 manufacturing process Methods 0.000 abstract description 6
- 239000002994 raw material Substances 0.000 abstract description 4
- 238000011084 recovery Methods 0.000 abstract description 3
- 230000000694 effects Effects 0.000 abstract description 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 abstract 3
- DXEOEEVKDQSFNT-UHFFFAOYSA-N ethyl formate piperidine Chemical compound C(=O)OCC.N1CCCCC1 DXEOEEVKDQSFNT-UHFFFAOYSA-N 0.000 abstract 3
- 239000001301 oxygen Substances 0.000 abstract 3
- 229910052760 oxygen Inorganic materials 0.000 abstract 3
- 239000000498 cooling water Substances 0.000 description 5
- 239000000463 material Substances 0.000 description 5
- 239000000047 product Substances 0.000 description 5
- 239000007787 solid Substances 0.000 description 5
- OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 4
- 238000001914 filtration Methods 0.000 description 4
- 238000003756 stirring Methods 0.000 description 4
- 238000007039 two-step reaction Methods 0.000 description 4
- 238000002425 crystallisation Methods 0.000 description 3
- 230000000994 depressogenic effect Effects 0.000 description 3
- 238000010438 heat treatment Methods 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 238000001816 cooling Methods 0.000 description 2
- 230000008025 crystallization Effects 0.000 description 2
- 238000006073 displacement reaction Methods 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 239000000706 filtrate Substances 0.000 description 2
- 239000007789 gas Substances 0.000 description 2
- 238000004128 high performance liquid chromatography Methods 0.000 description 2
- 150000002431 hydrogen Chemical class 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 238000010992 reflux Methods 0.000 description 2
- MFRIHAYPQRLWNB-UHFFFAOYSA-N sodium tert-butoxide Chemical compound [Na+].CC(C)(C)[O-] MFRIHAYPQRLWNB-UHFFFAOYSA-N 0.000 description 2
- 229910001220 stainless steel Inorganic materials 0.000 description 2
- 239000010935 stainless steel Substances 0.000 description 2
- DKPFZGUDAPQIHT-UHFFFAOYSA-N Butyl acetate Natural products CCCCOC(C)=O DKPFZGUDAPQIHT-UHFFFAOYSA-N 0.000 description 1
- VIZORQUEIQEFRT-UHFFFAOYSA-N Diethyl adipate Chemical compound CCOC(=O)CCCCC(=O)OCC VIZORQUEIQEFRT-UHFFFAOYSA-N 0.000 description 1
- 206010013786 Dry skin Diseases 0.000 description 1
- 206010054949 Metaplasia Diseases 0.000 description 1
- NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 1
- 229910000831 Steel Inorganic materials 0.000 description 1
- 238000013019 agitation Methods 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 238000006555 catalytic reaction Methods 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 238000009833 condensation Methods 0.000 description 1
- 230000005494 condensation Effects 0.000 description 1
- 238000006482 condensation reaction Methods 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- 230000006837 decompression Effects 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 210000003298 dental enamel Anatomy 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 125000004494 ethyl ester group Chemical group 0.000 description 1
- 239000012847 fine chemical Substances 0.000 description 1
- FUZZWVXGSFPDMH-UHFFFAOYSA-N hexanoic acid Chemical compound CCCCCC(O)=O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 description 1
- 238000005984 hydrogenation reaction Methods 0.000 description 1
- 230000015689 metaplastic ossification Effects 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 1
- 238000004064 recycling Methods 0.000 description 1
- 238000007363 ring formation reaction Methods 0.000 description 1
- 239000002002 slurry Substances 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 239000010959 steel Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 238000010792 warming Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/68—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member
- C07D211/72—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member with hetero atoms or with carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, directly attached to ring carbon atoms
- C07D211/78—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/02—Preparation by ring-closure or hydrogenation
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Hydrogenated Pyridines (AREA)
Abstract
The present invention provides a kind of preparation methods of 2 oxygen, 3 piperidine ethyl formate comprising following steps：S1, by after diethyl malonate and base catalyst mixing, acrylonitrile is added dropwise at 10~50 DEG C, 2 cyanoethyl diethyl malonates are obtained by the reaction；S2, the 2 cyanoethyl diethyl malonate and organic solvent, thunder Buddhist nun Co catalysts are reacted in the hydrogen gas atmosphere, at 75~130 DEG C, through being recrystallized to give 2 oxygen, 3 piperidine ethyl formate.Compared with prior art, the present invention has following advantageous effect：The manufacturing method of 2 oxygen, 3 piperidine ethyl formate provided by the present invention, is easy to get with raw material, easy to operate, and total recovery, up to 77% or more (improving 20%), therefore is very suitable for industrialized production compared with classical NFAlbertsm methods.
Description
Technical field
The present invention relates to a kind of preparation methods of 2- oxygen-ethyl nipecotate, belong to chemical intermediate technical field.
Background technology
2- oxygen-ethyl nipecotate is a kind of fine-chemical intermediate, for manufacturing brain health-care product epiphysin.Early in
1949, NFAlbertsm et al. just delivered 2- oxygen-ethyl nipecotate on american chemical magazine (JACS)
Synthetic method.They use diethyl malonate and acrylonitrile condensation reaction, obtain intermediate cyanoethyl diethyl malonate, so
Hydrogen cyclization is added to obtain product 2- oxygen-ethyl nipecotate in the presence of catalyst Raney Ni it afterwards, two-step reaction is always received
Rate 57.3%.Its reaction route is as follows：
Synthesis 2- oxygen-ethyl nipecotate method that NFAlbertsm is proposed has become the warp for synthesizing this compound
Allusion quotation method.The method that later scholar often directly quotes NFAlbertsm when publishing an article.Such as NJ in 2016
The article that Willis et al. is delivered on Green Chemistry, 2016,18,1313-1318 magazines.
2014, the bear of Hubei Kinsey pharmaceutcal corporation, Ltd, which opens et al., delivered the patent for preparing epiphysin
CN201410712934, wherein also using NFAlbertsm method synthetic intermediate 2- oxygen-ethyl nipecotate.But specially
This intermediate is not separated into catalysis in profit, but its aqueous solution is directly used in and is reacted in next step, therefore is reported without yield.
In conclusion so far from 1949,2- oxygen-ethyl nipecotate of domestic and foreign literature report is all made of in classics
NFAlbertsm methods, which has the shortcomings that yield is relatively low.Therefore, two step reaction yields how are improved, are dropped
Low cost of material reduces three-protection design pressure, is that production 2- oxygen-ethyl nipecotate intermediate is technically in the urgent need to address
The problem of.
Invention content
For the defects in the prior art, the object of the present invention is to provide a kind of preparations of 2- oxygen-ethyl nipecotate
Method.
The present invention is achieved by the following technical solutions：
The present invention provides a kind of preparation methods of 2- oxygen-ethyl nipecotate comprising following steps：
S1, by after diethyl malonate and base catalyst mixing, acrylonitrile is added dropwise at 10~50 DEG C, 2- is obtained by the reaction
Cyanoethyl diethyl malonate；
S2, by the 2- cyanoethyls diethyl malonate and organic solvent, thunder Buddhist nun Co catalysts in the hydrogen gas atmosphere, in 75
It is reacted at~130 DEG C, through being recrystallized to give the 2- oxygen-ethyl nipecotate.
Preferably, the reaction temperature in step S1 is 30~35 DEG C.
Preferably, the dosage of the base catalyst described in step S1 be diethyl malonate weight 0.3~
3%.
Preferably, the base catalyst includes NaOH, KOH, Na2CO3、K2CO3、NaOC2H5、 NaOC(OH3)3、
KOC(CH3)3At least one of.
Preferably, the weight ratio of the acrylonitrile described in step S1 and diethyl malonate is 1:(5~10),
Preferably 1:(7.5~8.5).
Preferably, the time for adding of the acrylonitrile is 1~10h, preferably 3~6h.
Preferably, the reaction temperature in step S2 is 100~105 DEG C.
Preferably, the thunder Buddhist nun Co catalysts and 2- cyanoethyl diethyl malonate weight ratios be (0.03~
0.3)：1, preferably (0.1~0.15)：1.
Preferably, the organic solvent and 2- cyanoethyl diethyl malonate weight ratios are (1~10)：1, it is described
Organic solvent is selected from one or more of ethyl alcohol, methanol, propyl alcohol, butanol, isopropanol.
Preferably, the reaction pressure of the hydrogen is 10~80kg/cm2, preferably 30~40kg/cm2, described
Recrystallization solvent used is in ethyl alcohol, isopropanol, butanol, ethyl acetate, butyl acetate, petroleum ether, methyl tertiary butyl ether(MTBE)
At least one.
Compared with prior art, the present invention has following advantageous effect：
The manufacturing method of 2- oxygen-ethyl nipecotate provided by the present invention, is easy to get with raw material, easy to operate, always
Yield, up to 77% or more (improving 20%), therefore is very suitable for industrial metaplasia compared with classical NFAlbertsm methods
Production.
Specific implementation mode
With reference to specific embodiment, the present invention is described in detail.Following embodiment will be helpful to the technology of this field
Personnel further understand the present invention, but the invention is not limited in any way.It should be pointed out that the ordinary skill of this field
For personnel, without departing from the inventive concept of the premise, various modifications and improvements can be made.These belong to the present invention
Protection domain.
Embodiment 1
Four mouthfuls of reaction bulbs of 1000mL dryings, are equipped with mechanical agitation, thermometer, dropping funel, reflux condensing tube.It is added third
Diethyl adipate 560g (3.5mol), basic catalyst sodium tert-butoxide 0.6g (solid powder) add acrylonitrile 70g (1.3mol)
Enter dropping funel.Acrylonitrile, exothermic heat of reaction, with water-bath controlling reaction temperature at 30~32 DEG C, 4 is added dropwise to reaction bulb under stiring
It adds within~5 hours.It is stirred 1 hour then at same thermotonus.
Feed liquid is transferred in 1000mL decompression short column rectifier units, raw material malonic acid is sloughed at 18~20mmHg of vacuum degree
Then diethylester improves vacuum degree to 0.6~0.8mmHg, steam the total 227.6g of positive fraction of 106~110 DEG C of fraction temperature,
Intermediate 2- cyanoethyl diethyl malonate G/C contents are 98.6%, reaction yield 80.9% (in terms of acrylonitrile).
By above-mentioned intermediate 227.6g, 1000g isopropanols, Raney Co catalyst 26g puts into 2 liters of stainless steel reaction under high pressures
In kettle.In hydrogen displacement kettle after air, hydrogen is depressed into 25kg/cm2, reaction generation, opens cooling water when being warming up to 75 DEG C.Control
Hydrogen input makes reaction pressure in 30~32kg/cm2Lower stable reaction, control cooling water make temperature be reacted at 95~105 DEG C.
Hydrogen is inhaled after 3.2 hours to stop, and is cooled to 40 DEG C, solid Raney Co catalyst is recovered by filtration in feed liquid.Filtrate is transferred to
In 2000mL reaction bulbs, heating boils off isopropanol, and petroleum ether and ethyl alcohol 1 is added in slurry in bottle：1 mixture 1000mL is tied again
Crystalline substance, is obtained by filtration crude product, and 60 DEG C of vacuum dries to obtain white solid 173.5g, HPLC analysis product 2- oxygen-ethyl nipecotate
Content is 99.6%, and hydrogenation reaction yield is 95.9%.Two-step reaction total recovery is 77.5%.
Embodiment 2
1000 liter glassed steel reaction vessels clean drying, in N2Under protection, diethyl malonate 620kg is put into
(3.87kmol), potassium tert-butoxide solid powder 0.9kg.72kg acrylonitrile is drawn in upper head tank.(1.35kmol) starts reaction
Kettle stirs, in interior temperature less than at 35 DEG C, in instilling acrylonitrile in reaction kettle in 5 hours.It adds after acrylonitrile then at 32 DEG C
Reaction 1 hour.
By reaction material liquid from the short column rectifying column that reaction kettle is transferred to 1000 liters of tower reactors.Vacuum system startup is made into vacuum
Degree opens overhead condensation pipe cooling water circulation, tower reactor reboiler introduces steam heating, in reflux ratio 1 up to 20~25mmHg：Under 1,
Steam solvent diethyl malonate.When diethyl malonate steams to the greatest extent, opening vacuum system multi-stage roots vacuum pump makes vacuum degree
Reach 1mmHg hereinafter, tower top a small amount of temperature occurs from 80~120 DEG C of fraction at this time.When fraction temperature is stablized at 121 DEG C,
Switch receiving vat, receives 121~125 DEG C of fraction 241kg altogether.GC detects intermediate 2- cyanoethyl diethyl malonate contents
98.2%.Reaction yield is calculated as 82.2% with acrylonitrile.
By above-mentioned intermediate 241kg, isopropanol 1200kg, it is anti-that catalyst Raney Co 28kg put into 2 liters of stainless steel high pressures
It answers in kettle.In hydrogen displacement kettle after air, hydrogen is depressed into 25kg/cm2, stirring is opened, 70 DEG C are slowly raised to jacket steam
More than, oxygen-absorbing reaction starts heat release.Cooling water cooling is opened at this time, and controlling reaction temperature steadily rises to 90~100 DEG C of reactions, controls
Hydrogen introducing makes pressure stability in 35~40kg/cm2Reaction.
4.5 inhaling hydrogen after hour to stop continuing at 100 DEG C, 35kg/cm2Lower reaction 1 hour.
Material in autoclave is cooled to 44 DEG C with cooling water, after the emptying of hydrogen residual voltage, uses N2Material is depressed into filter by gas,
In N2Raney Co catalyst is recovered by filtration under gas shielded.
Filtrate is introduced in 2000 liter enamels distillation crystallization kettle, under agitating and heating, solvent isopropanol is evaporated off.Then it takes advantage of
660kg petroleum ether and stirrings are added 0.5 hour in heat, gradually crystallisation by cooling, stirring interval start be not easy after preventing product from luming from
It is released under kettle.
Centrifugal filtration after the completion of crystallization obtains white solid 184kg after dry.HPLC detection levels are 99.6%, add hydrogen anti-
It is 96.4% to answer yield.
Two-step reaction total recovery is 79.2%.
Embodiment 3~8
Embodiment 3~8 repeats the operation of embodiment 2, but the malonic acid two that raw material diethyl malonate is steamed again with recycling
Ethyl ester adds fresh material to reach requirement inventory again；Next kettle is put into after the Raney Co catalyst recycled every time adds 0.5kg
Reaction；Product recrystallization operation all uses fresh solvent.
Reaction result such as following table：
Specific embodiments of the present invention are described above.It is to be appreciated that the invention is not limited in above-mentioned
Particular implementation, those skilled in the art can make various deformations or amendments within the scope of the claims, this not shadow
Ring the substantive content of the present invention.
Claims (10)
1. a kind of preparation method of 2- oxygen-ethyl nipecotate, which is characterized in that include the following steps：
S1, by after diethyl malonate and base catalyst mixing, acrylonitrile is added dropwise at 10~50 DEG C, 2- cyanoethyls are obtained by the reaction
Diethyl malonate；
S2, by the 2- cyanoethyls diethyl malonate and organic solvent, thunder Buddhist nun Co catalysts in the hydrogen gas atmosphere, in 75~
It is reacted at 130 DEG C, through being recrystallized to give the 2- oxygen-ethyl nipecotate.
2. the preparation method of 2- oxygen-ethyl nipecotate as described in claim 1, which is characterized in that anti-in step S1
It is 30~35 DEG C to answer temperature.
3. the preparation method of 2- oxygen-ethyl nipecotate as described in claim 1, which is characterized in that described in step S1
Base catalyst dosage be diethyl malonate weight 0.3~3%.
4. the preparation method of 2- oxygen-ethyl nipecotate as described in claim 1 or 3, which is characterized in that the base catalysis
Agent includes NaOH, KOH, Na2CO3、K2CO3、NaOC2H5、NaOC(OH3)3、KOC(CH3)3At least one of.
5. the preparation method of 2- oxygen-ethyl nipecotate as described in claim 1, which is characterized in that described in step S1
Acrylonitrile and diethyl malonate weight ratio be 1:(5~10).
6. the preparation method of 2- oxygen-ethyl nipecotate as described in claim 1, which is characterized in that the acrylonitrile
Time for adding is 1~10h.
7. the preparation method of 2- oxygen-ethyl nipecotate as described in claim 1, which is characterized in that anti-in step S2
It is 100~105 DEG C to answer temperature.
8. the preparation method of 2- oxygen-ethyl nipecotate as described in claim 1, which is characterized in that the thunder Buddhist nun cobalt is urged
Agent is (0.03~0.3) with 2- cyanoethyl diethyl malonate weight ratios：1.
9. the preparation method of 2- oxygen-ethyl nipecotate as described in claim 1, which is characterized in that the organic solvent
It is (1~10) with 2- cyanoethyl diethyl malonate weight ratios：1, the organic solvent be selected from ethyl alcohol, methanol, propyl alcohol, butanol,
One or more of isopropanol.
10. the preparation method of 2- oxygen-ethyl nipecotate as described in claim 1, which is characterized in that the hydrogen it is anti-
It is 10~80kg/cm to answer pressure2, the solvent used in the recrystallization is selected from ethyl alcohol, isopropanol, butanol, ethyl acetate, acetic acid fourth
At least one of ester, petroleum ether, methyl tertiary butyl ether(MTBE).
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN115010623A (en) * | 2022-06-29 | 2022-09-06 | 福建科宏生物工程股份有限公司 | Preparation method of 2-cyanoethyl diethyl malonate |
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2018
- 2018-05-22 CN CN201810497214.2A patent/CN108484484B/en active Active
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN115010623A (en) * | 2022-06-29 | 2022-09-06 | 福建科宏生物工程股份有限公司 | Preparation method of 2-cyanoethyl diethyl malonate |
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