CN1332930C - Method for preparing precursor of cycloprothrin - Google Patents
Method for preparing precursor of cycloprothrin Download PDFInfo
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- CN1332930C CN1332930C CNB2005100285702A CN200510028570A CN1332930C CN 1332930 C CN1332930 C CN 1332930C CN B2005100285702 A CNB2005100285702 A CN B2005100285702A CN 200510028570 A CN200510028570 A CN 200510028570A CN 1332930 C CN1332930 C CN 1332930C
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- ethoxyl phenenyl
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C67/00—Preparation of carboxylic acid esters
- C07C67/30—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group
- C07C67/317—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group by splitting-off hydrogen or functional groups; by hydrogenolysis of functional groups
- C07C67/327—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group by splitting-off hydrogen or functional groups; by hydrogenolysis of functional groups by elimination of functional groups containing oxygen only in singly bound form
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C67/00—Preparation of carboxylic acid esters
- C07C67/30—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group
- C07C67/333—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group by isomerisation; by change of size of the carbon skeleton
- C07C67/343—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group by isomerisation; by change of size of the carbon skeleton by increase in the number of carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C67/00—Preparation of carboxylic acid esters
- C07C67/30—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group
- C07C67/333—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group by isomerisation; by change of size of the carbon skeleton
- C07C67/343—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group by isomerisation; by change of size of the carbon skeleton by increase in the number of carbon atoms
- C07C67/347—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group by isomerisation; by change of size of the carbon skeleton by increase in the number of carbon atoms by addition to unsaturated carbon-to-carbon bonds
Abstract
The present invention relates to a convenient and low-cost process for synthesizing cycloprothrin and the precursor thereof. The process conveniently and cheaply prepares a key intermediate compound, namely 4-ethoxy phenyl lactate ester dehydrated under the acid condition to obtain corresponding methyl acrylate. 2-(4-ethoxy) phenyl methyl acrylate reacts with dichloro carbene to generate dichlor carbene ternary ring of which the compound is conventionally saponified into acid. After being chloridized, acylation reacts with cyanohydrin to obtain the cycloprothrin.
Description
Technical field:
The present invention relates to the new process of precursor of cycloprothrin.
Background technology:
Cycloprothrin (cycloprothrin) is a kind of hydrobiont low toxicities such as fish to be can be used for the synthetic pyrethroid insecticide in paddy field, and structural formula is as follows:
The document synthetic method is from p-hydroxyphenylaceticacid, make the ethoxy-phenylacetic acid ethyl ester through etherificate, esterification, get 2-(to ethoxyl phenenyl) acrylate with formaldehyde condensation again, be reacted into triatomic ring with the dichlorocarbene then, resaponifying becomes acid, make at last behind the acyl chlorides with cyanalcohol react cycloprothrin, route is as follows:
Above operational path is long, and yield is low, and the intermediate major part is high boiling oily liquids, need carry out molecular distillation and purify, and difficult purifying causes cost very high.Concrete document is: 1.US4262014; 2.AU502950; 3.EP0003670.
Summary of the invention:
The problem to be solved in the present invention is convenient and prepares this key intermediate of 4-ethoxyl phenenyl lactate cheaply, and then the processing method of a kind of convenience and synthetic cheaply cycloprothrin and precursor thereof is provided.4-ethoxyl phenenyl lactate structure is:
Wherein R is the straight chain or the branched alkane of 1-6 carbon.
4-ethoxyl phenenyl lactate prepares under following reaction conditions by phenyl ethyl ether and pyruvate.This compounds can be used for convenient and synthetic cheaply cycloprothrin.
The reaction formula of synthetic 4-ethoxyl phenenyl lactate is:
In the formula, R as previously mentioned.
Promptly under a kind of Lewis acid effect, add or do not add under the condition of alkali, the direct and pyruvate in the electron rich position of phenyl ethyl ether
Carry out Friedel-Crafts reaction and prepare above-mentioned 2-ary lactate.Described Lewis acid is recommended as: aluminum chloride, zinc chloride, iron(ic) chloride, titanium tetrachloride, nickelous chloride, tin tetrachloride, zirconium tetrachloride, tindichloride, boron trifluoride diethyl etherate, trimethylchlorosilane, trifluoromethanesulfonic acid zinc, copper trifluoromethanesulfcomposite, Bismuth triflate.Described alkali is triethylamine, diethylamine, pyridine, piperidines, diisopropylethylamine, alkali-metal carbonate, alkali-metal oxyhydroxide, metal oxide.Described reaction is recommended in the following organic solvent to be carried out: tetrahydrofuran (THF), methylene dichloride, oil of mirbane, chlorobenzene, ethylene dichloride, methyl tertiary butyl ether, Nitromethane 99Min., benzene, tetracol phenixin, the perhaps mixture of above solvent.The ratio of amount of substance is recommended as between the described reactant: phenyl ethyl ether: pyruvate: alkali: Lewis acid=1.0: 1.0～1.5: 1.0～3.0: 0.5～2.5.The reactions steps of recommending is as follows:
1. with in phenyl ethyl ether and pyruvate and the alkali adding organic solvent
2. then this system is cooled to subzero 50 and spends zero degree, begin to add Lewis acid under stirring;
3. spend to reaction between 5 degree subzero 50, after reacting completely reaction mixture is added in the water of the 0-5 degree that stirs the cancellation reaction;
4. the concentrated underpressure distillation of extraction liquid removes solvent and gets the product ary lactate.
The invention provides the novel method of synthetic cycloprothrin and precursor thereof, this method can make things convenient for and synthesize cheaply the precursor dichlorocarbene triatomic ring compound of cycloprothrin:
Phenyl ethyl ether under these conditions with pyruvate react 4-ethoxyl phenenyl lactate:
2.4-the ethoxyl phenenyl lactate (is recommended as and adds tosic acid and Resorcinol under acidic conditions according to routine operation, further be recommended as the tosic acid of adding (1-10) % and (0.1-5) Resorcinol of %, described per-cent is the weight percentage with respect to lactate, and temperature of reaction is recommended as reflux) the corresponding acrylate of dehydration generation:
3.2-carrying out the dichlorocarbene under the effect of alkali, (4-ethoxyl phenenyl) acrylate and chloroform react generation dichlorocarbene triatomic ring:
This step reacts and further recommends to have two kinds of methods to make the heat effect when technology is amplified production better control, thereby has improved original technology owing to the violent unmanageable shortcoming of carbene reaction heat release, and reaction yield greatly improves.Method has:
1) add a kind of organic solvent in the Cabbeen reaction system, make two phase reaction steadily carry out, described organic solvent is recommended as toluene, and the amount of described organic solvent is recommended as the weight with respect to 0.5 to 6 times of substrate acrylate
2) alkali that will produce Cabbeen changes Potassium monofluoride/aluminum oxide into by sodium hydroxide, and reaction is at room temperature very steadily carried out;
The first method concrete steps are recommended as: 4-ethoxyl phenenyl lactate is dewatered under acidic conditions to be generated corresponding acrylate and is dissolved in the chloroform, add phase-transfer catalyst then and with respect to the toluene of 0.5 to 6 times of weight of substrate acrylate, the strong caustic of Dropwise 5 0% between controlled temperature 40-65 degree then.Adding the back reacts between 40-60 to raw material and disappears.Described phase-transfer catalyst is a quaternary ammonium salt, is recommended as Tetramethylammonium hydroxide, Tetrabutyl amonium bromide, and tetrabutylammonium chloride, benzyl trimethyl ammonium chloride, benzyltriethylammoinium chloride, benzyl triethyl ammonium bromide, special recommendation is a benzyltriethylammoinium chloride.
The second method concrete steps are recommended as: 4-ethoxyl phenenyl lactate is dewatered under acidic conditions to be generated corresponding acrylate and is dissolved in the acetonitrile, add 5 to 15 times of Potassium monofluoride/aluminum oxide and less water again to the substrate acrylate, add chloroform at last, at room temperature stirring reaction to raw material disappears again.
The above-mentioned dichlorocarbene's triatomic ring compound that obtains is again through the acid that is saponified into of routine, after the chloride with cyanalcohol react cycloprothrin, referring to 1.US4262014; 2.AU502950; 3.EP0003670.
The processing method that the invention provides a kind of convenience and synthesize cycloprothrin cheaply, it is low to have overcome the conventional art yield, and the intermediate major part is high boiling oily liquids, need carry out molecular distillation and purify, difficult purifying causes the very high technical barrier of cost.In addition, the present invention further the heat effect that technology is amplified when producing of the optimization by reaction conditions is controlled better, and has improved technology in the past because the violent unmanageable shortcoming of carbene reaction heat release, and reaction yield improves greatly.
Embodiment
Following examples help to understand this patent but this patent protection domain is not limited to this.
Embodiment 1
40 gram phenyl ethyl ethers and 40 gram Pyruvic Acid Ethyl esters are added in 400 milliliters of methylene dichloride, add 31 gram aluminum oxide again, then this system is cooled to subzero 45 degree, begin to add titanium tetrachloride, keep under the zero temperature 45, under this temperature, react then to subzero 20 degree.Till gas-chromatography tracking reaction raw materials no longer reduces.Spend to reaction between 5 degree subzero 10, after reacting completely reaction mixture is added in the water of the 0-5 degree that stirs the cancellation reaction.The concentrated underpressure distillation of extraction liquid removes solvent and gets product ary lactate 43 grams, yield 55%.The compound characterization data:
FTIR(neat)：3506，2983，1728，1247cm
-1；
1H?NMR(CDCl
3，300MHz)δ＝7.46(d，J＝9.0Hz，2H)，6.87(d，J＝8.7Hz，2H)，4.25(q，J＝7.1Hz，2H)，4.02(q，J＝7.0Hz，2H)，3.77(s，3H)，3.72(s，1H)，1.75(s，3H)，1.41(t，J＝7.0Hz，3H)，1.27(t，J＝7.1Hz，3H)；
13C?NMR(CDCl
3，75MHz)δ＝175.6，158.3，134.7，126.3，113.9，75.1，63.2，62.0，26.5，14.6，13.9；MS(EI)m/e?238(M+，3.5)，165(100)，43(59.7)；Anal.Calcd?forC
13H
18O
4：C，65.53；H，7.61.Found：C，65.59；H，7.66.
Embodiment 2
40 gram phenyl ethyl ethers and 40 gram Pyruvic Acid Methyl esters are added in 400 milliliters of methylene dichloride, add 31 gram barium oxide again, then this system is cooled to subzero 45 degree, begin to add titanium tetrachloride, keep under the zero temperature 45, under this temperature, react then to subzero 20 degree.Till gas-chromatography tracking reaction raw materials no longer reduces.Spend to reaction between 5 degree subzero 10, after reacting completely reaction mixture is added in the water of the 0-5 degree that stirs the cancellation reaction.The concentrated underpressure distillation of extraction liquid removes solvent and gets product ary lactate 41 grams, yield 51%.
FTIR(neat)：3523，2983，1721，1245cm
-1；
1H?NMR(CDCl
3，300MHz)δ＝7.45(d，J＝9.0Hz，2H)，6.87(d，J＝8.7Hz，2H)，4.02(q，J＝7.0Hz，2H)，3.76(s，3H)，3.72(s，1H)，1.76(s，3H)，1.41(t，J＝7.0Hz，3H)；
13C?NMR(CDCl
3，75MHz)δ＝176.2，158.4，134.5，126.3，113.9，75.3，63.2，53.0，26.5，14.7；MS(EI)m/e?224(M+，5.9)，165(100)，43(36.9)；Anal.Calcd?for?C
12H
16O
4：C，64.27；H，7.19.Found：C，64.11；H，7.11.
Embodiment 3
500 gram 4-ethoxyl phenenyl ethyl lactates are joined in 2000 milliliters of chloroforms, add 2.5 gram Resorcinol and 20 gram tosic acid then, reflux is divided water, gas phase follow the tracks of react to raw material less than 1%, steam 1000 milliliters of chloroforms altogether.Cooling with 400 milliliters of washed twice of 10% sodium hydroxide, adds 3.6 gram benzyltriethylammoinium chlorides then.System is heated to 55 degree, begins to drip the aqueous sodium hydroxide solution of 1800 grams 50%, temperature control 50-65 degree.React very violent in the dropping process, be difficult to control.Once there were three generations to dash the material phenomenon.Dripping then has raw material propylene acid esters saponification phenomenon to take place too slowly.Add the back and the 50-60 degree between be incubated to raw material less than 1%.Add 2000 milliliters of ethylene dichloride, phase-splitting, more once with 1000 milliliters of ethylene dichloride extractions.Merge oil phase, dry concentrate remove behind the solvent dichlorocarbene's triatomic ring product, not purified can be directly repurity after the step saponification down.Roll over hundred yields 41%, HPLC purity 98%.
Embodiment 4
500 gram 4-ethoxyl phenenyl ethyl lactates are joined in 2000 milliliters of chloroforms, add 2.5 gram Resorcinol and 20 gram tosic acid then, reflux is divided water, gas phase follow the tracks of react to raw material less than 1%, steam 1000 milliliters of chloroforms altogether.Cooling with 400 milliliters of washed twice of 10% sodium hydroxide, adds 2000 milliliters of toluene and 3.6 gram benzyltriethylammoinium chlorides then.System is heated to 55 degree, begins to drip the aqueous sodium hydroxide solution of 1800 grams 50%, temperature control 50-65 degree.Add the back and the 50-60 degree between be incubated to raw material less than 1%.Add 2000 milliliters of ethylene dichloride, phase-splitting, more once with 1000 milliliters of ethylene dichloride extractions.Merge oil phase, dry concentrate remove behind the solvent dichlorocarbene's triatomic ring product, not purified can be directly repurity after the step saponification down.Roll over hundred yields 90%, HPLC purity 98%.
Embodiment 5
500 gram 4-ethoxyl phenenyl ethyl lactates are joined in 2000 milliliters of chloroforms, add 2.5 gram Resorcinol and 20 gram tosic acid then, reflux is divided water, gas phase follow the tracks of react to raw material less than 1%, steam 1000 milliliters of chloroforms altogether.Cooling with 400 milliliters of washed twice of 10% sodium hydroxide, adds 500 milliliters of toluene and 3.6 gram benzyltriethylammoinium chlorides then.System is heated to 55 degree, begins to drip the aqueous sodium hydroxide solution of 1800 grams 50%, temperature control 50-65 degree.Before not adding, find to have the saponification phenomenon.Add the back and the 50-60 degree between be incubated to raw material less than 1%.Add 2000 milliliters of ethylene dichloride, phase-splitting, more once with 1000 milliliters of ethylene dichloride extractions.Merge oil phase, dry concentrate remove behind the solvent dichlorocarbene's triatomic ring product, not purified can be directly repurity after the step saponification down.Roll over hundred yields 25%
Embodiment 6
50 gram 4-ethoxyl phenenyl ethyl lactates are joined in 200 milliliters of chloroforms, add 0.25 gram Resorcinol and 2 gram tosic acid then, reflux is divided water, gas phase follow the tracks of react to raw material less than 1%, steam 100 milliliters of chloroforms altogether.Cooling with 40 milliliters of washed twice of 10% sodium hydroxide, adds 300 milliliters of toluene and 0.36 gram Tetrabutyl amonium bromide then.System is heated to 55 degree, begins to drip the aqueous sodium hydroxide solution of 180 grams 50%, temperature control 50-65 degree.Reaction needs 3 to 4 hours approximately.Add the back and the 50-60 degree between be incubated to raw material less than 1%.Add 200 milliliters of ethylene dichloride, phase-splitting, more once with 50 milliliters of ethylene dichloride extractions.Merge oil phase, dry concentrate remove behind the solvent dichlorocarbene's triatomic ring product, not purified can be directly repurity after the step saponification down.Roll over hundred yields 36%
Embodiment 7
20 gram 4-ethoxyl phenenyl ethyl lactates are joined in 80 milliliters of chloroforms, add 0.1 gram Resorcinol and 0.8 gram tosic acid then, reflux is divided water, gas phase follow the tracks of react to raw material less than 1%, steam 40 milliliters of chloroforms altogether.Cooling with 40 milliliters of washed twice of 10% sodium hydroxide, adds 200 milliliters of acetonitriles and 5.4 gram water then.Add 100 gram Potassium monofluoride/aluminum oxide again.Add 12 milliliters of chloroforms at last.Reaction system is at room temperature (25-30 degree) stirring reaction.GC follow the tracks of react to raw material less than 1%.Filter, filtrate adds 200 milliliters of ethylene dichloride and 100 ml waters, phase-splitting, more once with 50 milliliters of ethylene dichloride extractions.Merge oil phase, washing once, dry concentrate remove behind the solvent dichlorocarbene's triatomic ring product, not purified can be directly repurity after the step saponification down.Roll over hundred yields 66%, HPLC purity 97%.
Embodiment 8
20 gram 4-ethoxyl phenenyl ethyl lactates are joined in 80 milliliters of chloroforms, add 0.1 gram Resorcinol and 0.8 gram tosic acid then, reflux is divided water, gas phase follow the tracks of react to raw material less than 1%, steam 40 milliliters of chloroforms altogether.Cooling with 40 milliliters of washed twice of 10% sodium hydroxide, adds 200 milliliters of acetonitriles and 5.4 gram water then.Add 150 gram Potassium monofluoride/aluminum oxide again.Add 12 milliliters of chloroforms at last.Reaction system is at room temperature (25-30 degree) stirring reaction.GC follow the tracks of react to raw material less than 1%.Filter, filtrate adds 200 milliliters of ethylene dichloride and 100 ml waters, phase-splitting, more once with 50 milliliters of ethylene dichloride extractions.Merge oil phase, washing once, dry concentrate remove behind the solvent dichlorocarbene's triatomic ring product, not purified can be directly repurity after the step saponification down.Roll over hundred yields 90%, HPLC purity 97%.
Embodiment 9
Ternary cyclic ester in 10 liters reactor behind the adding carbene reaction, and use the 2.0L dissolve with ethanol; Pre-configured 4%NaOH (being dissolved in 4.8L water) solution is joined system, and the heating reflux reaction HPLC that begins to take a sample after 1 hour analyze to follow the tracks of, and is complete until raw material reaction, concentrates the ethanol of removing the overwhelming majority, cooling.After remainder water solution was washed with ethylene dichloride (2 * 2 L), the ice-water bath cooling added hcl acidifying to pH=2 down, separates out solid.Suction filtration, filter cake are neutral with washing to elutant.This filter cake dewaters with 4 L refluxing toluenes; Steam 1L toluene (surplus 3 L) after water is taken out of to no longer including, the white plates crystal is separated out in cooling.Suction filtration is drained, weigh 740g product 1-(4-ethoxyl phenenyl)-2,2-two Cyclopropanoyl Chlorides-1-carboxylic acid, yield 90%.FTIR(KBr)：3218，2990，1732，1515?cm
-1；
1H?NMR(CDCl
3，300?MHz)δ＝11.3(s，br，1H)，7.36(d，J＝8.5Hz，2H)，6.88(d，J＝8.3Hz，2H)，4.02(q，J＝6.8Hz，2H)，2.59(d，J＝7.8Hz，1H)，2.04(d，J＝7.9Hz，1H)，1.40(t，J＝6.8Hz，3H)；
13C?NMR(CDCl
3，75MHz)δ＝173.8，159.2，131.9，125.4，114.1，63.4，61.8，43.9，30.6，14.8；MS(EI)m/e?274(M+，22.8)，239(100)，193(99.8)，165(99.3)，147(59.0)，131(63.5)；Anal.Calcd?for?C
12H
12Cl
2O
3：C，52.39；H，4.40.Found：C，52.34；H，4.43.
Embodiment 10
To ethoxyl phenenyl-2,2-two Cyclopropanoyl Chlorides-1-acid joins in 30 milliliters of sulfur oxychlorides with 27.5 gram 1-, and reflux one hour does not have hydrogenchloride to emit substantially.Decompression steams the excess chlorination sulfoxide then.The cooling back adds 50 milliliters of toluene.Between being added dropwise to then-phenoxy group-Cyanobenzyl Alcohol (24.8 gram) and the solution of 12 gram pyridines in 30 milliliters of toluene.Room temperature reaction 12 hours.Wash washing, saturated common salt water washing successively with aqueous sodium carbonate.Dry then concentrating.Get product 48 gram cycloprothrins, HPLC purity 99%.
Claims (13)
1. the new process of the precursor dichlorocarbene triatomic ring compound of a synthetic cycloprothrin, it is characterized in that being dewatered under acidic conditions by 4-ethoxyl phenenyl lactate generates corresponding 2-(4-ethoxyl phenenyl) acrylate; 2-(4-ethoxyl phenenyl) acrylate and chloroform carry out the dichlorocarbene and react generation dichlorocarbene triatomic ring under the effect of alkali:
Wherein R is the straight or branched alkane of 1 to 6 carbon.
2. method according to claim 1, it is characterized in that further comprising phenyl ethyl ether and pyruvate react 4-ethoxyl phenenyl lactate:
Wherein R is the straight or branched alkane of 1 to 6 carbon.
3. method according to claim 1 and 2 is characterized in that under the Lewis acid effect, adds or does not add under the condition of alkali, the direct and pyruvate in the electron rich position of phenyl ethyl ether
Carry out Friedel-Crafts reaction and prepare above-mentioned 4-ethoxyl phenenyl lactate; Described Lewis acid is: aluminum chloride, zinc chloride, iron(ic) chloride, titanium tetrachloride, nickelous chloride, tin tetrachloride, zirconium tetrachloride, tindichloride, boron trifluoride diethyl etherate, trimethylchlorosilane, trifluoromethanesulfonic acid zinc, copper trifluoromethanesulfcomposite or Bismuth triflate; Described alkali is triethylamine, diethylamine, pyridine, piperidines, diisopropylethylamine, alkali-metal carbonate, alkali-metal oxyhydroxide or metal oxide.
4. method according to claim 3 is characterized in that described Friedel-Crafts reaction carries out: tetrahydrofuran (THF), methylene dichloride, oil of mirbane in following organic solvent, chlorobenzene, ethylene dichloride, methyl tertiary butyl ether, Nitromethane 99Min., benzene, tetracol phenixin, the perhaps mixture of above solvent; The ratio of amount of substance is between the described reactant: phenyl ethyl ether: pyruvate: alkali: Lewis acid=1.0: 1.0～1.5: 1.0～3.0: 0.5～2.5.
5. method according to claim 3 is characterized in that described Friedel-Crafts reaction comprises the steps:
1). in phenyl ethyl ether and pyruvate and alkali adding organic solvent;
2). then this system is cooled to subzero 50 and spends zero degree, begin to add Lewis acid under stirring;
3). spend to reaction between 5 degree subzero 50, after reacting completely the reaction mixture adding is stirred
In the water of 0-5 degree, the cancellation reaction;
4). the concentrated underpressure distillation of extraction liquid removes solvent and gets product 4-ethoxyl phenenyl lactate.
6. method according to claim 1 and 2 is characterized in that described acidic conditions is to carry out under acidic conditions according to routine operation adding tosic acid and Resorcinol.
7. method according to claim 1 and 2 is characterized in that adding toluene in the Cabbeen reaction system.
8. method according to claim 7, it is characterized in that 4-ethoxyl phenenyl lactate dewatered under acidic conditions and generate corresponding acrylate and be dissolved in the chloroform, add phase-transfer catalyst and 0.5 to 6 times of toluene with respect to substrate acrylate weight, dropping sodium solution is 40～65 ℃ of reactions.
9. method according to claim 8 is characterized in that described phase-transfer catalyst is a quaternary ammonium salt.
10. method according to claim 1 and 2, the alkali that it is characterized in that described generation Cabbeen is sodium hydroxide or Potassium monofluoride/aluminum oxide.
11. method according to claim 10, it is characterized in that 4-ethoxyl phenenyl lactate dewatered under acidic conditions and generate corresponding acrylate and be dissolved in the acetonitrile, add 5 to 15 times with respect to the Potassium monofluoride/aluminum oxide of substrate acrylate weight and water, adding chloroform, at room temperature reaction.
12. method according to claim 1 and 2 is characterized in that further comprising that the dichlorocarbene's triatomic ring compound with obtaining is saponified into acid, after the chloride with cyanalcohol react cycloprothrin.
13. compound with following structure:
Wherein R is the straight or branched alkane of 1 to 6 carbon.
Priority Applications (1)
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|---|---|---|---|
| CNB2005100285702A CN1332930C (en) | 2005-08-05 | 2005-08-05 | Method for preparing precursor of cycloprothrin |
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| CNB2005100285702A CN1332930C (en) | 2005-08-05 | 2005-08-05 | Method for preparing precursor of cycloprothrin |
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| CN1733694A CN1733694A (en) | 2006-02-15 |
| CN1332930C true CN1332930C (en) | 2007-08-22 |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN106632168A (en) * | 2016-12-26 | 2017-05-10 | 上海生农生化制品股份有限公司 | Synthetic method of lactate derivative as well as product and application thereof |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU502950B2 (en) * | 1976-11-26 | 1979-08-16 | Commonwealth Scientific And Industrial Research Organisation | Insecticidal resarch organization |
| US4262014A (en) * | 1975-11-26 | 1981-04-14 | Commonwealth Scientific And Industrial Research Organization | Insecticidal esters |
| CN1281436A (en) * | 1997-12-12 | 2001-01-24 | 细胞途径公司 | N-Benzyl-3-indenylacetamides derivatives for treating neoplasia |
-
2005
- 2005-08-05 CN CNB2005100285702A patent/CN1332930C/en not_active Expired - Fee Related
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4262014A (en) * | 1975-11-26 | 1981-04-14 | Commonwealth Scientific And Industrial Research Organization | Insecticidal esters |
| AU502950B2 (en) * | 1976-11-26 | 1979-08-16 | Commonwealth Scientific And Industrial Research Organisation | Insecticidal resarch organization |
| CN1281436A (en) * | 1997-12-12 | 2001-01-24 | 细胞途径公司 | N-Benzyl-3-indenylacetamides derivatives for treating neoplasia |
Non-Patent Citations (3)
| Title |
|---|
| Synthesis of p-substituted atropic and atrolactic acidsusingbenzyltrimethylammonium chloride. Cho,Youn Sang 等,Soul Taehakkyo Yakhak Nonmunjip.,Vol.9 1984 * |
| Synthesis of p-substituted atropic and atrolactic acidsusingbenzyltrimethylammonium chloride. Cho,Youn Sang 等,Soul Taehakkyo Yakhak Nonmunjip.,Vol.9 1984;α-Fluoro Analogues of Inflammation Inhibiting α-Arylpropionic Acids Manfred Schlosser等,tetrahedron,Vol.52 No.24 1996 * |
| α-Fluoro Analogues of Inflammation Inhibiting α-Arylpropionic Acids Manfred Schlosser等,tetrahedron,Vol.52 No.24 1996 * |
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