CN113121432A - Synthesis method of aliphatic alkene with guide group - Google Patents
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- CN113121432A CN113121432A CN202110408979.6A CN202110408979A CN113121432A CN 113121432 A CN113121432 A CN 113121432A CN 202110408979 A CN202110408979 A CN 202110408979A CN 113121432 A CN113121432 A CN 113121432A
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- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D215/38—Nitrogen atoms
- C07D215/40—Nitrogen atoms attached in position 8
Abstract
The invention discloses a method for synthesizing aliphatic alkene with a guide group, which relates to the technical field of organic chemistry and comprises the following steps: s1, adding sodium hydride and super-dry tetrahydrofuran into a dry chemical container containing magnetons under the atmosphere of inert gas, cooling the solution to 0 ℃ through ice bath, dropwise adding ethyl cyanoacetate at the temperature, reacting at the temperature of 0 ℃ for 20-40 minutes, then adding 3-bromopropylene, heating the reaction solution to room temperature, reacting for 4-8 hours, and further performing post-treatment and purification to obtain 3-cyano-2-oxahexyl-5-ethyl enoate; s2, adding an aqueous solution of sodium hydroxide and a tetrahydrofuran solution into the obtained 3-cyano-2-oxahexyl-5-olefine acid ethyl ester, and reacting for 15-20 hours at room temperature. The method obtains a new compound, can be widely used for coupling reaction of various inert olefins, and has the characteristics of good functional group compatibility, mild reaction conditions, cheap and easily obtained raw materials, high yield and simple post-treatment and purification.
Description
Technical Field
The invention relates to the technical field of organic chemistry, in particular to a method for synthesizing aliphatic alkene with a guide group.
Background
The inert olefin with the guide group is widely applied to the research of organic synthesis methodology and the research of total synthesis so as to synthesize complex drug molecules, and the regioselectivity and the chemical selectivity of the reaction can be improved by controlling the guide group, so that the inert olefin is a powerful tool to assist the inert olefin to carry out various coupling reactions so as to construct complex C-C bonds, C-N bonds, C-S bonds, C-O bonds and the like.
The chemical name of the compound is 2-cyano-N- (quinoline-8-yl) pent-4-enamide, and the compound is light yellow solid.
The existing inert olefin with a guide group has limited types and cannot be widely applied, and generally has higher required reaction conditions, high raw material cost and lower yield, so that more waste is caused in the operation process, and the post-treatment and purification are difficult.
Therefore, there is a need to provide a method for synthesizing aliphatic alkenes with directing groups to solve the above technical problems.
Disclosure of Invention
The present invention is directed to a method for synthesizing an aliphatic olefin having a directing group, which solves the problems of the prior art.
In order to achieve the purpose, the invention provides the following technical scheme: a method for synthesizing aliphatic alkene with a guide group comprises the following steps:
s1, adding sodium hydride and super-dry tetrahydrofuran which are stored in 60% mineral oil into a dry chemical container containing magnetons under the inert gas atmosphere, the solution is cooled to 0 ℃ through ice bath, ethyl cyanoacetate is added dropwise at the temperature, 3-bromopropylene is added after 20-40 minutes of reaction at the temperature of 0 ℃, heating the reaction solution to room temperature, reacting for 4-8 hours, adding 15-30 ml of water into the reaction system to quench when the raw materials are completely converted, extracting for three times by using 15-30 ml of ethyl acetate, collecting all organic phases, washing twice by using 30-40 ml of water, washing once by using 30-40 ml of saturated salt, drying the organic phases by using anhydrous magnesium sulfate, removing insoluble substances by filtration, removing ethyl acetate by rotary evaporation, and then obtaining ethyl 3-cyano-2-oxahexyl-5-enoate by column chromatography;
s2, adding 1.0-1.5 equivalent of 2M sodium hydroxide aqueous solution into the obtained 3-cyano-2-oxahexyl-5-ethyl enoate, adding 2-3 ml ethanol solution into each mole of 3-cyano-2-oxahexyl-5-ethyl enoate, reacting for 15-20 hours at room temperature, removing ethanol by rotary evaporation after the reaction is finished, adding water with the same volume as that of the ethanol into the reaction liquid after the rotary drying, washing for three times by using dichloromethane with the same volume, adding 2M hydrochloric acid into the water phase for acidification, adjusting the pH value to 4.0, and extracting by using dichloromethane to obtain 3-cyano-2-oxahexane-5-ethyl enoate;
s3, adding 0.8 equivalent of 8-aminoquinoline, 1.0 equivalent of HATU and 1.55 equivalent of pyridine into the obtained 3-cyano-2-oxahexane-5-olefine acid, using ultra-dry dichloromethane as a solvent, reacting at room temperature for 16-24 hours until the raw materials are completely converted, removing the dichloromethane by rotary evaporation, adding 60-100mL of ethyl acetate to dissolve the reaction solution, adding 80-120mL of saturated sodium bicarbonate, extracting for three times, adding 80-120mL of saturated saline solution into the mixed organic phase, washing, carrying out rotary drying, and carrying out flash column chromatography to obtain the pure product 2-cyano-N- (quinolin-8-yl) pent-4-enamide.
Further, in the step S1, the inert gas used in the inert atmosphere is argon.
Further, in the step S1, the molar ratio of ethyl cyanoacetate, 3-bromopropylene and sodium hydride is 3: 1:1.
further, in the step S1, the mass fraction of sodium hydride is 10% to 30%, the mass fraction of ethyl cyanoacetate is 40% to 80%, the mass fraction of 3-bromopropene is 10% to 30%, and the molar volume ratio of 3-bromopropene to ultra-dry tetrahydrofuran is 10 mmol: 40 mL.
Further, in the step S2, the mass fraction of the ethyl 3-cyano-2-oxahexyl-5-enoate is 1% to 3%, the 1.0 to 1.5 equivalents of 2M sodium hydroxide in water solution is 5% to 10%, the water solution is 70% to 95%, and the molar volume ratio of the ethyl 3-cyano-2-oxahexyl-5-enoate to tetrahydrofuran is 10 mmol: 15 mL.
Further, in the step S3, the mass fraction of the 3-cyano-2-oxahexane-5-enoic acid is 15% to 30%, the mass fraction of the 8-aminoquinoline is 10% to 25%, the mass fraction of the HATU is 15% to 30%, the mass fraction of the pyridine is 20% to 50%, and the molar volume ratio of the 8-aminoquinoline to the extra-dry dichloromethane is 1 mmol: 3 mL.
Further, in the step S2, the molar ratio of the ethyl 3-cyano-2-oxahexyl-5-enoate to the sodium hydroxide to the water is 1: 4: 50.
further, in the step S2, the volume of the 2M hydrochloric acid added was 5 mL.
Further, in the step S3, the dichloromethane used is ultra-dry dichloromethane, and the mobile phase of flash column chromatography is a mixture of mobile phases with a molar ratio of 1: 3 petroleum ether: purifying with ethyl acetate silica gel chromatographic column.
Compared with the prior art, the invention has the beneficial effects that: the synthesis method of the aliphatic alkene with the guide group obtains a new compound through the method, the compound can be widely used for coupling reaction of various inert alkenes, the synthesis route has the characteristics of good functional group compatibility, mild reaction conditions, cheap and easily obtained raw materials, high yield and simple post-treatment and purification.
Drawings
FIG. 1 is a hydrogen spectrum of 2-cyano-N- (quinolin-8-yl) pent-4-enamide in the method for synthesizing aliphatic alkene with a directing group according to the present invention.
Detailed Description
The technical solutions in the embodiments of the present invention will be clearly and completely described below with reference to the drawings in the embodiments of the present invention, and it is obvious that the described embodiments are only a part of the embodiments of the present invention, and not all of the embodiments. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.
The first embodiment is as follows:
s1, adding sodium hydride and super-dry tetrahydrofuran which are stored in 60% mineral oil into a dry chemical container containing magnetons under the inert gas atmosphere, the solution is cooled to 0 ℃ through ice bath, ethyl cyanoacetate is added dropwise at the temperature, 3-bromopropylene is added after 20-40 minutes of reaction at the temperature of 0 ℃, heating the reaction solution to room temperature, reacting for 4-8 hours, adding 15-30 ml of water into the reaction system to quench when the raw materials are completely converted, extracting for three times by using 15-30 ml of ethyl acetate, collecting all organic phases, washing twice by using 30-40 ml of water, washing once by using 30-40 ml of saturated salt, drying the organic phases by using anhydrous magnesium sulfate, removing insoluble substances by filtration, removing ethyl acetate by rotary evaporation, and then obtaining ethyl 3-cyano-2-oxahexyl-5-enoate by column chromatography;
s2, adding 1.0-1.5 equivalent of 2M sodium hydroxide aqueous solution into the obtained 3-cyano-2-oxahexyl-5-ethyl enoate, adding 2-3 ml ethanol solution into each mole of 3-cyano-2-oxahexyl-5-ethyl enoate, reacting for 15-20 hours at room temperature, removing ethanol by rotary evaporation after the reaction is finished, adding water with the same volume as that of the ethanol into the reaction liquid after the rotary drying, washing for three times by using dichloromethane with the same volume, adding 2M hydrochloric acid into the water phase for acidification, adjusting the pH value to 4.0, and extracting by using dichloromethane to obtain 3-cyano-2-oxahexane-5-ethyl enoate;
s3, adding 0.8 equivalent of 8-aminoquinoline, 1.0 equivalent of HATU and 1.55 equivalent of pyridine into the obtained 3-cyano-2-oxahexane-5-olefine acid, using ultra-dry dichloromethane as a solvent, reacting at room temperature for 16-24 hours until the raw materials are completely converted, removing the dichloromethane by rotary evaporation, adding 60-100mL of ethyl acetate to dissolve the reaction solution, adding 80-120mL of saturated sodium bicarbonate, extracting for three times, adding 80-120mL of saturated saline solution into the mixed organic phase, washing, carrying out rotary drying, and carrying out flash column chromatography to obtain the pure product 2-cyano-N- (quinolin-8-yl) pent-4-enamide.
In step S1, the inert gas used in the inert atmosphere is argon.
In the step S1, the molar ratio of ethyl cyanoacetate, 3-bromopropene and sodium hydride is 3: 1:1.
in the step S1, the mass fraction of sodium hydride is 10% to 30%, the mass fraction of ethyl cyanoacetate is 40% to 80%, the mass fraction of 3-bromopropene is 10% to 30%, and the molar volume ratio of 3-bromopropene to ultra-dry tetrahydrofuran is 10 mmol: 40 mL.
In the step S2, the mass fraction of the ethyl 3-cyano-2-oxahexyl-5-enoate is 1% to 3%, the 1.0 to 1.5 equivalents of sodium hydroxide in the aqueous solution of 2M sodium hydroxide is 5% to 10%, the aqueous solution is 70% to 95%, and the molar volume ratio of the ethyl 3-cyano-2-oxahexyl-5-enoate to tetrahydrofuran is 10 mmol: 15 mL.
In the step S3, the mass fraction of the 3-cyano-2-oxahexane-5-enoic acid is 15% to 30%, the mass fraction of the 8-aminoquinoline is 10% to 25%, the mass fraction of the HATU is 15% to 30%, the mass fraction of the pyridine is 20% to 50%, and the molar volume ratio of the 8-aminoquinoline to the extra-dry dichloromethane is 1 mmol: 3 mL.
In the step S2, the molar ratio of the ethyl 3-cyano-2-oxahexyl-5-enoate to the sodium hydroxide to the water is 1: 4: 50.
in the step S2, the volume of 2M hydrochloric acid added was 5 mL.
In the step S3, the dichloromethane used is ultra-dry dichloromethane, and the mobile phase of flash column chromatography is a mixture of mobile phases with a molar ratio of 1: 3 petroleum ether: purifying with ethyl acetate silica gel chromatographic column.
HATU is a condensing agent with good effect, 3-cyano-2-oxahexane-5-olefine acid and 8-aminoquinoline are main condensing compounds, pyridine plays a part of the role of alkali, ultra-dry dichloromethane is a solvent with good solubility, the four substances, namely 8-aminoquinoline, 3-cyano-2-oxahexane-5-olefine acid, HATU and pyridine are matched according to the proportion of 1:1.3:1.3:2, so that good reaction effect can be achieved, wherein 3-cyano-2-oxahexane-5-olefine acid can be replaced by 4-pentenoic acid, 2-methyl-4-pentanoic acid, 2-phenyl-4-pentanoic acid and other olefine acids and derivatives thereof;
the boiling point of the 2-cyano-N- (quinolin-8-yl) pent-4-enamide is 599.1 + -45.0 ℃, the density is 1.244 + -0.06 g/cm3, and the acidity coefficient is 10.54 + -0.43;
the boiling point of 2-methyl-N- (quinolin-8-yl) pent-4-enamide is 450.3. + -. 28.0 ℃, the density is 1.136. + -. 0.06g/cm3, and the acidity factor is 12.92. + -. 0.43.
Reacting 2-cyano-N- (quinoline-8-yl) pent-4-enamide with aryl halide, adding 2.5-10 mol% of catalyst, 5-20 mol% of ligand, 3-5 equivalents of lithium acetate and 20-25 equivalents of water, adding an alcohol solvent such as 2, 3-butanediol, and reacting at 100-140 ℃ to finally realize a coupling reaction.
Example two:
s1, adding sodium hydride and super-dry tetrahydrofuran which are stored in 60% mineral oil into a dry chemical container containing magnetons under the inert gas atmosphere, the solution is cooled to 0 ℃ through ice bath, ethyl cyanoacetate is added dropwise at the temperature, 3-bromopropylene is added after 20-40 minutes of reaction at the temperature of 0 ℃, heating the reaction solution to room temperature, reacting for 4-8 hours, adding 15-30 ml of water into the reaction system to quench when the raw materials are completely converted, extracting for three times by using 15-30 ml of ethyl acetate, collecting all organic phases, washing twice by using 30-40 ml of water, washing once by using 30-40 ml of saturated salt, drying the organic phases by using anhydrous magnesium sulfate, removing insoluble substances by filtration, removing ethyl acetate by rotary evaporation, and then obtaining ethyl 3-cyano-2-oxahexyl-5-enoate by column chromatography;
s2, adding 1.0-1.5 equivalent of 2M sodium hydroxide aqueous solution into the obtained 3-cyano-2-oxahexyl-5-ethyl enoate, adding 2-3 ml ethanol solution into each mole of 3-cyano-2-oxahexyl-5-ethyl enoate, reacting for 15-20 hours at room temperature, removing ethanol by rotary evaporation after the reaction is finished, adding water with the same volume as that of the ethanol into the reaction liquid after the rotary drying, washing for three times by using dichloromethane with the same volume, adding 2M hydrochloric acid into the water phase for acidification, adjusting the pH value to 4.0, and extracting by using dichloromethane to obtain 3-cyano-2-oxahexane-5-ethyl enoate;
s3, adding 0.8 equivalent of 8-aminoquinoline, 1.0 equivalent of HATU and 1.55 equivalent of pyridine into the obtained 3-cyano-2-oxahexane-5-olefine acid, using ultra-dry dichloromethane as a solvent, reacting at room temperature for 16-24 hours until the raw materials are completely converted, removing the dichloromethane by rotary evaporation, adding 60-100mL of ethyl acetate to dissolve the reaction solution, adding 80-120mL of saturated sodium bicarbonate, extracting for three times, adding 80-120mL of saturated saline solution into the mixed organic phase, washing, carrying out rotary drying, and carrying out flash column chromatography to obtain the pure product 2-cyano-N- (quinolin-8-yl) pent-4-enamide.
In step S1, the inert gas used in the inert atmosphere is argon.
In the step S1, the molar ratio of ethyl cyanoacetate, 3-bromopropene and sodium hydride is 3: 1:1.
in the step S1, the mass fraction of sodium hydride is 10% to 30%, the mass fraction of ethyl cyanoacetate is 40% to 80%, the mass fraction of 3-bromopropene is 10% to 30%, and the molar volume ratio of 3-bromopropene to ultra-dry tetrahydrofuran is 10 mmol: 40 mL.
In the step S2, the mass fraction of the ethyl 3-cyano-2-oxahexyl-5-enoate is 1% to 3%, the 1.0 to 1.5 equivalents of sodium hydroxide in the aqueous solution of 2M sodium hydroxide is 5% to 10%, the aqueous solution is 70% to 95%, and the molar volume ratio of the ethyl 3-cyano-2-oxahexyl-5-enoate to tetrahydrofuran is 10 mmol: 15 mL.
In the step S3, the mass fraction of the 3-cyano-2-oxahexane-5-enoic acid is 15% to 30%, the mass fraction of the 8-aminoquinoline is 10% to 25%, the mass fraction of the HATU is 15% to 30%, the mass fraction of the pyridine is 20% to 50%, and the molar volume ratio of the 8-aminoquinoline to the extra-dry dichloromethane is 1 mmol: 3 mL.
In the step S2, the molar ratio of the ethyl 3-cyano-2-oxahexyl-5-enoate to the sodium hydroxide to the water is 1: 4: 50.
in the step S2, the volume of 2M hydrochloric acid added was 5 mL.
In the step S3, the dichloromethane used is ultra-dry dichloromethane, and the mobile phase of flash column chromatography is a mixture of mobile phases with a molar ratio of 1: 3 petroleum ether: purifying with ethyl acetate silica gel chromatographic column.
HATU is a condensing agent with good effect, 3-cyano-2-oxahexane-5-olefine acid and 8-aminoquinoline are main condensing compounds, pyridine plays a part of the role of alkali, ultra-dry dichloromethane is a solvent with good solubility, the four substances, namely 8-aminoquinoline, 3-cyano-2-oxahexane-5-olefine acid, HATU and pyridine are matched according to the proportion of 1:1.3:1.3:2, so that good reaction effect can be achieved, wherein 3-cyano-2-oxahexane-5-olefine acid can be replaced by 4-pentenoic acid, 2-methyl-4-pentanoic acid, 2-phenyl-4-pentanoic acid and other olefine acids and derivatives thereof;
the boiling point of the 2-cyano-N- (quinolin-8-yl) pent-4-enamide is 599.1 + -45.0 ℃, the density is 1.244 + -0.06 g/cm3, and the acidity coefficient is 10.54 + -0.43;
the boiling point of 2-methyl-N- (quinolin-8-yl) pent-4-enamide is 450.3. + -. 28.0 ℃, the density is 1.136. + -. 0.06g/cm3, and the acidity factor is 12.92. + -. 0.43.
Reacting 2-cyano-N- (quinoline-8-yl) pent-4-enamide with alkyl halide, adding 2.5-10 mol% of photocatalyst, 5-20 mol% of ligand and 3.0 equivalent of cesium carbonate, adding a solvent capable of dissolving the cesium carbonate, such as a mixed solution of 2- (isopropylamino) ethanol and methanol in a ratio of 40:1, and reacting under illumination to realize free radical coupling reaction.
It will be evident to those skilled in the art that the invention is not limited to the details of the foregoing illustrative embodiments, and that the present invention may be embodied in other specific forms without departing from the spirit or essential attributes thereof. The present embodiments are therefore to be considered in all respects as illustrative and not restrictive, the scope of the invention being indicated by the appended claims rather than by the foregoing description, and all changes which come within the meaning and range of equivalency of the claims are therefore intended to be embraced therein. Any reference sign in a claim should not be construed as limiting the claim concerned.
Claims (9)
1. A method for synthesizing aliphatic alkene with a guide group is characterized in that: the method comprises the following steps:
s1, adding sodium hydride and super-dry tetrahydrofuran which are stored in 60% mineral oil into a dry chemical container containing magnetons under the inert gas atmosphere, the solution is cooled to 0 ℃ through ice bath, ethyl cyanoacetate is added dropwise at the temperature, 3-bromopropylene is added after 20-40 minutes of reaction at the temperature of 0 ℃, heating the reaction solution to room temperature, reacting for 4-8 hours, adding 15-30 ml of water into the reaction system to quench when the raw materials are completely converted, extracting for three times by using 15-30 ml of ethyl acetate, collecting all organic phases, washing twice by using 30-40 ml of water, washing once by using 30-40 ml of saturated salt, drying the organic phases by using anhydrous magnesium sulfate, removing insoluble substances by filtration, removing ethyl acetate by rotary evaporation, and then obtaining ethyl 3-cyano-2-oxahexyl-5-enoate by column chromatography;
s2, adding 1.0-1.5 equivalent of 2M sodium hydroxide aqueous solution into the obtained 3-cyano-2-oxahexyl-5-ethyl enoate, adding 2-3 ml ethanol solution into each mole of 3-cyano-2-oxahexyl-5-ethyl enoate, reacting for 15-20 hours at room temperature, removing ethanol by rotary evaporation after the reaction is finished, adding water with the same volume as that of the ethanol into the reaction liquid after the rotary drying, washing for three times by using dichloromethane with the same volume, adding 2M hydrochloric acid into the water phase for acidification, adjusting the pH value to 4.0, and extracting by using dichloromethane to obtain 3-cyano-2-oxahexane-5-ethyl enoate;
s3, adding 0.8 equivalent of 8-aminoquinoline, 1.0 equivalent of HATU and 1.55 equivalent of pyridine into the obtained 3-cyano-2-oxahexane-5-olefine acid, using ultra-dry dichloromethane as a solvent, reacting at room temperature for 16-24 hours until the raw materials are completely converted, removing the dichloromethane by rotary evaporation, adding 60-100mL of ethyl acetate to dissolve the reaction solution, adding 80-120mL of saturated sodium bicarbonate, extracting for three times, adding 80-120mL of saturated saline solution into the mixed organic phase, washing, carrying out rotary drying, and carrying out flash column chromatography to obtain the pure product 2-cyano-N- (quinolin-8-yl) pent-4-enamide.
2. The method for synthesizing aliphatic alkene with guiding group according to claim 1, wherein: in step S1, the inert gas used in the inert atmosphere is argon.
3. The method for synthesizing aliphatic alkene with guiding group according to claim 1, wherein: in the step S1, the molar ratio of ethyl cyanoacetate, 3-bromopropene and sodium hydride is 3: 1:1.
4. the method for synthesizing aliphatic alkene with guiding group according to claim 1, wherein: in the step S1, the mass fraction of sodium hydride is 10% to 30%, the mass fraction of ethyl cyanoacetate is 40% to 80%, the mass fraction of 3-bromopropene is 10% to 30%, and the molar volume ratio of 3-bromopropene to ultra-dry tetrahydrofuran is 10 mmol: 40 mL.
5. The method for synthesizing aliphatic alkene with guiding group according to claim 1, wherein: in the step S2, the mass fraction of the ethyl 3-cyano-2-oxahexyl-5-enoate is 1% to 3%, the 1.0 to 1.5 equivalents of sodium hydroxide in the aqueous solution of 2M sodium hydroxide is 5% to 10%, the aqueous solution is 70% to 95%, and the molar volume ratio of the ethyl 3-cyano-2-oxahexyl-5-enoate to tetrahydrofuran is 10 mmol: 15 mL.
6. The method for synthesizing aliphatic alkene with guiding group according to claim 1, wherein: in the step S3, the mass fraction of the 3-cyano-2-oxahexane-5-enoic acid is 15% to 30%, the mass fraction of the 8-aminoquinoline is 10% to 25%, the mass fraction of the HATU is 15% to 30%, the mass fraction of the pyridine is 20% to 50%, and the molar volume ratio of the 8-aminoquinoline to the extra-dry dichloromethane is 1 mmol: 3 mL.
7. The method for synthesizing aliphatic alkene with guiding group according to claim 1, wherein: in the step S2, the molar ratio of the ethyl 3-cyano-2-oxahexyl-5-enoate to the sodium hydroxide to the water is 1: 4: 50.
8. the method for synthesizing aliphatic alkene with guiding group according to claim 1, wherein: in the step S2, the volume of 2M hydrochloric acid added was 5 mL.
9. The method for synthesizing aliphatic alkene with guiding group according to claim 1, wherein: in the step S3, the dichloromethane used is ultra-dry dichloromethane, and the mobile phase of flash column chromatography is a mixture of mobile phases with a molar ratio of 1: 3 petroleum ether: purifying with ethyl acetate silica gel chromatographic column.
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| CN113563180A (en) * | 2021-07-26 | 2021-10-29 | 广东嘉博制药有限公司 | (E) Preparation method of (E) -4-ene-1, 8-octanedioic acid |
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