WO2016153094A1 - Nouveau procédé de préparation d'un dérivé de 3-alcoxy-thiophène - Google Patents

Nouveau procédé de préparation d'un dérivé de 3-alcoxy-thiophène Download PDF

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WO2016153094A1
WO2016153094A1 PCT/KR2015/002962 KR2015002962W WO2016153094A1 WO 2016153094 A1 WO2016153094 A1 WO 2016153094A1 KR 2015002962 W KR2015002962 W KR 2015002962W WO 2016153094 A1 WO2016153094 A1 WO 2016153094A1
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formula
compound
stirring
degrees celsius
solvent
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Korean (ko)
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심유란
주건군
나하나
황성관
박장하
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비스메르 주식회사
미래파인켐 주식회사
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Priority to PCT/KR2015/002962 priority Critical patent/WO2016153094A1/fr
Publication of WO2016153094A1 publication Critical patent/WO2016153094A1/fr

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
    • C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
    • C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
    • C07D333/06—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to the ring carbon atoms
    • C07D333/08—Hydrogen atoms or radicals containing only hydrogen and carbon atoms
    • C07D333/10—Thiophene
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
    • C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
    • C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
    • C07D333/26—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur 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
    • C07D333/30—Hetero atoms other than halogen
    • C07D333/32—Oxygen atoms

Definitions

  • the present invention relates to a novel method for preparing 3-alkoxythiophene derivatives, and more particularly, to a method for effectively mass-producing 3-alkoxythiophene derivatives.
  • 3-alkoxythiophenes of formula I are important intermediates in the synthesis of prostaglandins and are known to be difficult to synthesize. 3-alkoxythiophene is also an important block in the manufacture of pharmaceuticals.
  • Non-Patent Document 1 Synthetic Metals 2014, 188, 156-160
  • Non-Patent Document 2 New J. Chem. 2010, 34, 2558-2563
  • Non-Patent Document 3 J. Med. Chem., 1997, 40 (25), 4053-4068
  • Non-Patent Document 4 J. Het. Chem. 2003, 40 (1), 1-23
  • Non-Patent Document 5 Bioorg. Med. Chem. Lett. 2001, 11 (11), 1407-1410
  • Non-Patent Document 6 J. Med. Chem., 2003, 46 (23), 4910-4925
  • One problem to be solved by the present invention is to provide a method for effectively preparing a 3-alkoxythiophene derivative.
  • Another problem to be solved by the present invention is to provide a 3-alkoxythiophene derivative prepared by the production method of the present invention.
  • the present invention comprises the steps of (A) reacting a compound of Formula 2 with a compound of Formula 3 to obtain a reactant, and then hydrolyzing the reactant to prepare a compound of Formula 4; (B) preparing a compound of formula 5 by monoalkylation reaction of the compound of formula 4 in the presence of a solvent; And (C) decarboxylation of the prepared compound of Formula 5 by heating to a temperature of 80 ° C to 300 ° C without a solvent, wherein the 3-alkoxythiophene derivative of Formula 1 to provide.
  • R 1 and R 2 are each independently alkyl and X is halogen.
  • R 1 and R 2 are each C 1 -C 4 alkyl, more preferably methyl.
  • X may be bromine.
  • the reactant of step (A) may be a compound of formula 2-1.
  • R 1 and R 2 are each independently alkyl.
  • R 1 and R 2 are each C 1 -C 4 alkyl, more preferably R 1 and R 2 may be each methyl.
  • Step (A) may include (A-1) reacting the compound of Formula 2 with the compound of Formula 3 in the presence of a solvent and a base to obtain the reactant; And (A-2) hydrolyzing the reactant produced in step (A-1) with a base in an aqueous solution to prepare the compound of Chemical Formula 4.
  • Step (A-1) is a contact step of contacting the solvent (A-1a) with the compound of Formula 2 at 15 to 30 degrees Celsius to obtain a contact;
  • (A-1b) a first addition step of obtaining an additive by adding a base to the contact obtained in the contacting step of (A-1a) at 15 ° C to 30 ° C;
  • (A-1c) a first stirring step of obtaining the first stirring by stirring the additive of the addition step of (A-1b) at 35 degrees Celsius to 45 degrees;
  • (A-1d) a second addition step of obtaining an additive by adding the compound of Formula 3 to the first stirring material;
  • (A-1e) a secondary stirring step of obtaining the secondary agitated by stirring the additive of the secondary addition step of (A-1d) at 80 degrees Celsius to 100 degrees Celsius;
  • (A-1f) extracting the secondary stirring product of step (A-1e) with a nonpolar solvent to obtain an extract, and concentrating the extract to obtain a concentrate.
  • the solvent of step (A-1) may be at least one nonpolar solvent selected from dimethylformamide, dichloromethane, benzene, toluene, methane tetrachloride, ethyl ether, isopropyl ether and dimethyl sulfoxide.
  • the base of step (A-1) may be at least one selected from K 2 CO 3 , Na 2 CO 3 , KOH, and NaOH.
  • the nonpolar solvent of step (A-1f) may be at least one selected from dimethylformamide, dichloromethane, benzene, toluene, tetramethane, ethyl ether, isopropyl ether and dimethyl sulfoxide.
  • the step (A-2) is (A-2a) an addition step of obtaining an additive by adding a base in an aqueous solution to the reaction of the step (A-1) at 15 degrees Celsius to 30 degrees Celsius; (A-2b) agitation step of obtaining the agitated by stirring the additive of the addition step of (A-2a) at 70 to 90 degrees Celsius; And (A-2c) may include the step of adding an acid to the stirring of the stirring step (A-2b).
  • the base of step (A-2) may be at least one selected from K 2 CO 3 , Na 2 CO 3 , KOH, and NaOH.
  • the step (A-2c) may be a step of adding the acid to pH 1 after lowering the temperature of the stirred product of the stirring step (A-2b) to -10 degrees to 0 degrees Celsius.
  • the acid of step (A-2c) may be hydrochloric acid, nitric acid, sulfuric acid or acetic acid.
  • Step (B) comprises the steps of contacting (Ba) a solvent to obtain a contact by contacting the compound of Formula 4 at 0 to 10 degrees Celsius; (Bb) a dropping step of adding dropwise addition of sulfuric acid to the contact of step (Ba) at 0 ° C to 10 ° C; (Bc) the stirring step of stirring the dropwise addition of the step (Bb) at 10 to 30 degrees Celsius for 2 to 6 hours to obtain a stirred product; And (Bd) may comprise a purification step of purifying the agitated.
  • the solvent of step (Ba) may be one or more polar solvents selected from methanol, isopropyl alcohol and butanol.
  • the purification step of the step (Bd) may include a filtration step, an extraction step, a concentration step and a drying step.
  • the purification step may be carried out with one or more nonpolar solvents selected from dimethylformamide, dichloromethane, benzene, toluene, methane tetrachloride, ethyl ether, isopropyl ether and dimethyl sulfoxide.
  • Step (C) may be performed at 160 to 240 degrees Celsius.
  • Step (C) may be carried out for 6 to 48 hours.
  • the compound of Formula 2 may be commercially available or prepared.
  • the preparation method includes the steps of: (a) contacting the solvent with metal sodium at -10 to 5 degrees Celsius to obtain a contact; (b) a first dropping step of adding a compound of formula 6 to the contact of step (a) at -10 ° C to 10 ° C to obtain a first dropper; (c) a second dropping step of dropping the compound of formula 7 to the first dropping product produced in step (b) at -10 ° C to 10 ° C to obtain a second dropping product; (d) agitation step of obtaining a final agitation by stirring the secondary dropping product produced in step (c) at 15 degrees Celsius to 30 degrees Celsius; (e) adding an acid to the final stirring to obtain an additive; And (f) may further comprise the step of preparing a compound of Formula 2 comprising a purification step of extracting and concentrating the additive obtained in step (e).
  • R 2 is alkyl.
  • R 2 is C 1 -C 4 alkyl, more preferably methyl.
  • the step (e) may be an acidification step to pH 2 with an acid.
  • Extraction of step (f) may be carried out with one or more nonpolar solvents selected from dimethylformamide, dichloromethane, benzene, toluene, methane tetrachloride, ethyl ether, isopropyl ether and dimethyl sulfoxide.
  • nonpolar solvents selected from dimethylformamide, dichloromethane, benzene, toluene, methane tetrachloride, ethyl ether, isopropyl ether and dimethyl sulfoxide.
  • the present invention also provides a 3-alkoxythiophene derivative of the formula (1) prepared by the production method of the present invention.
  • 3-alkoxythiophene derivatives can be mass produced at high efficiency.
  • FIG. 1 is a flowchart illustrating an embodiment of a ball invention.
  • the present invention provides a method for preparing the compound of formula (1).
  • R 1 is alkyl, preferably C 1 to C 4 alkyl, more preferably methyl.
  • the compound of formula 1 is a 3-alkoxythiophene derivative and is an important intermediate in prostaglandin synthesis and is known to act as an important block in the manufacture of pharmaceuticals as an intermediate that is difficult to synthesize (J. Med. Chem., 1997, 40). (25), pp 4053-4068; J. Het. Chem. 2003, 40 (1) 1-23; Bioorg. Med. Chem. Lett. 2001, 11 (11), 1407-1410; J. Med. Chem. , 2003, 46 (23), pp 4910-4925. Et al.). Therefore, in Formula 1, R 1 is alkyl, preferably C 1 to C 4 alkyl, more preferably methyl, 3-alkoxythiophene derivatives can be used for prostaglandin synthesis, pharmaceutical preparation It can be used for.
  • an embodiment of the present invention includes (A) preparing a compound of Formula 4, (B) preparing a compound of Formula 5, and (C) a decarboxylation step.
  • Step (A) is a step of preparing a compound of Formula 4 by reacting a compound of Formula 2 with a compound of Formula 3 to obtain a reactant, and then hydrolyzing the reactant.
  • R 1 and R 2 are each independently alkyl, preferably C 1 to C 4 alkyl, and more preferably methyl.
  • X is halogen, preferably bromine.
  • the compound name of the compound of Formula 2 is alkyl 3-hydroxythiophene-2-carboxylate.
  • step (B) is a step of preparing a compound of Formula 5 by monoalkylation reaction of the compound of Formula 4 prepared in the presence of a solvent.
  • R 1 is alkyl, preferably C 1 to C 4 alkyl, more preferably methyl.
  • step (C) is a step of decarboxylation by heating the compound of Formula 5 prepared to a temperature of 80 to 300 degrees Celsius without a solvent.
  • the compound of formula 2 may be one produced or marketed by the following scheme 1 as a starting material of the present method. This is an embodiment according to the present invention, and the present invention is not limited thereto.
  • the compound of Chemical Formula 2 according to the present invention may be prepared by other production methods known in the art, and commercially available ones may be purchased and used.
  • alkyl of Formula 2 3-hydroxythiophene-2-carboxylate can be prepared.
  • the contacting step may be a step of contacting the solvent with the sodium metal at -10 to 5 degrees Celsius to obtain a contact.
  • the solvent is not limited thereto as long as it is a polar solvent, but may be, for example, methanol, isopropyl alcohol, and / or butanol, and the like.
  • the contact may preferably be contact at -4 degrees Celsius to 4 degrees Celsius.
  • the first dropping step is to dissolve the compound of Formula 6 in the same solvent as the solvent of the contacting step (a) dropwise at -10 to 10 degrees Celsius to the contact of the contacting step to obtain a first dropping product It may be a step.
  • the dropwise addition may be preferably dropwise at -4 degrees Celsius to 4 degrees Celsius.
  • the second dropping step is a second dropping product by dissolving the compound of formula 7 in the same kind of solvent as the solvent of the contacting step and (b) dropping the dropping product in the first dropping step at -10 to 10 degrees Celsius It may be a step of obtaining.
  • the dropwise addition may be preferably dropwise at -4 degrees Celsius to 4 degrees Celsius.
  • the stirring step may be a step of obtaining the final stirring by stirring the resulting secondary dropping product at 15 degrees Celsius to 30 degrees after the end of the second dropping step. At this time, the compound of Formula 2 is produced.
  • the final agitated product is in a state containing no starting material.
  • the stirring of the stirring step may be carried out for 1.5 hours to 4 hours, preferably 1.5 hours to 2 hours.
  • the agitation may preferably be agitation at 18 degrees to 26 degrees Celsius.
  • the addition step is to obtain an additive by adding an acid (acid) to such a final stirring, it may be an acidification step.
  • the addition step may be a step of concentrating the final agitated acid and then acidifying the acid to pH 2 with an acid.
  • the acid (aicd) according to the present invention is not limited to this as long as it is a material that can adjust the pH, for example, may be hydrochloric acid, nitric acid, sulfuric acid and / or acetic acid and the like.
  • the purification step may be a step of extracting and concentrating the additive, specifically, an extraction step of extracting the additive with a solvent to obtain an extract; And concentrating the extract of the extracting step to obtain a concentrate.
  • a purification step a compound of formula 2 having higher purity may be prepared.
  • the extraction step may be a step of obtaining an extract by extracting the additive with a solvent.
  • the additive may be extracted with a solvent to obtain a solvent layer, and the solvent layer may be washed with water.
  • the solvent is not limited to this as long as it is a nonpolar solvent, but may be, for example, dimethylformamide, dichloromethane, benzene, toluene, methane tetrachloride, ethyl ether, isopropyl ether and / or dimethyl sulfoxide and the like.
  • the concentration step may be a step of removing the water contained in the extract by using anhydrous MgSO 4 and the like, by removing the solvent by a rotary concentrator, etc., to obtain a concentrate by concentration.
  • the compound of Chemical Formula 2 may be prepared up to 200 to 500 g at a time.
  • the compound of Formula 1 may be prepared according to the synthesis route of Scheme 2.
  • the reactant may be a compound of Formula 2-1.
  • R 1 and R 2 are each independently alkyl, preferably R 1 and R 2 are each C 1 -C 4 alkyl, more preferably, R 1 and R 2 are each methyl Can be.
  • the compound name of the compound of Formula 2-1 is alkyl 3- (2-alkoxy-2-oxoethoxy) thiophene-2-carboxylate.
  • Step (A) comprises the steps of (A-1) reacting a compound of Formula 2 with a compound of Formula 3 in the presence of a solvent and a base to obtain a reactant; And (A-2) hydrolyzing the reactant produced in step (A-1) with a base in an aqueous solution to prepare a compound of Formula 4.
  • the base in the aqueous solution state is the base is dispersed or dissolved in water, since the base in the aqueous solution state containing water, hydrolysis of the reactant may proceed.
  • step (A-1) as a specific example according to the present invention is the contact step (A-1a), the first addition step (A-1b), the first stirring step (A-1c), the second addition step ( A-1d), a second stirring step (A-1e) and a purification step (A-1f) may be included.
  • the contacting step may be a step of contacting the solvent with the compound of Formula 2 at 15 degrees to 30 degrees Celsius, preferably at 18 degrees to 25 degrees Celsius to obtain a contact.
  • the solvent is not limited to this as long as it is a nonpolar solvent, but may be, for example, dimethylformamide, dichloromethane, benzene, toluene, methane tetrachloride, ethyl ether, isopropyl ether and / or dimethyl sulfoxide and the like.
  • the primary addition step may be a step of obtaining an additive by adding a base to the contact obtained in the contacting step at 15 degrees to 30 degrees Celsius, preferably 18 degrees to 25 degrees Celsius.
  • the base is not limited thereto, but may be, for example, K 2 CO 3 , Na 2 CO 3 , KOH and / or NaOH, and the like.
  • the additive obtained in the first adding step may be stirred at 35 degrees to 45 degrees Celsius, preferably 38 degrees to 42 degrees Celsius, to obtain a first stirring substance. Stirring of the first stirring step may be carried out for 20 to 50 minutes.
  • the second addition step may be a step of obtaining the additive by adding the compound of Formula 3 to the first stirring.
  • the second stirring step is a step of obtaining a secondary stirring material as a final stirring material after stirring at 80 degrees to 100 degrees Celsius, preferably 88 degrees to 93 degrees Celsius after the completion of the second addition step, the starting material Compound of Formula 2-1 is generated from the compound of. After completion of stirring, water is added to obtain a white solid. Stirring of the second stirring step may be carried out for 1.5 to 4 hours. Preferably it may be carried out for 1.5 hours to 2 hours.
  • This final agitator can be purified to a compound of formula 2-1 through a purification step.
  • the purification step is to extract the final stirred with a solvent to obtain an extract; And concentrating the extract of the extracting step to obtain a concentrate. Through such a purification step, a more pure compound of formula 2-1 may be prepared.
  • the extraction step is a step of obtaining an extract by extracting the stirring with a solvent.
  • the solvent may be extracted by extracting a stirring substance with a solvent, and the solvent layer may be washed with water.
  • the solvent is not limited to this as long as it is a nonpolar solvent, but may be, for example, dimethylformamide, dichloromethane, benzene, toluene, methane tetrachloride, ethyl ether, isopropyl ether and / or dimethyl sulfoxide and the like.
  • the concentration step is a step of obtaining a concentrate by removing the water contained in the extract using anhydrous MgSO 4 and the like, by removing the solvent with a rotary concentrator or the like.
  • the step (A-2) may include an addition step (A-2a), a stirring step (A-2b), and an acid addition step (A-2c).
  • the addition step may be a step of obtaining an additive by adding a base in an aqueous solution state at 15 degrees to 30 degrees Celsius, preferably 18 degrees to 25 degrees Celsius, to the reactant of step (A-1).
  • the base is not limited thereto, but may be, for example, NaOH, Na 2 CO 3 , KOH and / or K 2 CO 3 , and the like.
  • the stirring step may be a step of obtaining the stirring by stirring the additive of the addition step at 70 degrees to 90 degrees Celsius, preferably 75 to 80 degrees Celsius. Stirring of the stirring step can be carried out for 30 minutes to 2 hours.
  • the acid addition step may be a step of acidifying by adding acid to the agitate.
  • the acid addition step may be a step of lowering the temperature of the stirring water to -10 degrees Celsius to 0 degrees, and then adding the acid to pH 1.
  • Such acid (aicd) is not limited to this as long as it is a material that can adjust the pH, for example, may be hydrochloric acid, nitric acid, sulfuric acid and / or acetic acid and the like.
  • the compound of formula 4 can be prepared in large quantities up to 500 g-5000 g at a time.
  • Step (B) is a monoalkylation reaction of the compound of formula 4 in the presence of a solvent to prepare a compound of formula 5.
  • the compound of Formula 5 may be prepared from the compound of Formula 4 through the contacting step Ba, the dropping step Bb, the stirring step Bc, and the purification step Bd.
  • the contacting step may be a step of contacting the solvent with the compound of formula 4 at 0 to 10 degrees Celsius, preferably at 0 to 5 degrees Celsius to obtain a contact.
  • the solvent is not limited thereto as long as it is a polar solvent, but may be, for example, methanol, isopropyl alcohol, and / or butanol, and the like.
  • the dropping step may be a step of adding dropwise sulfuric acid (H 2 SO 4 ) to the contact of the contacting step at 0 to 10 degrees Celsius, preferably 4 to 8 degrees Celsius.
  • dropwise sulfuric acid H 2 SO 4
  • the stirring step may be a step of stirring the dropping product of the dropping step at 10 degrees to 30 degrees Celsius for 2 hours to 6 hours, preferably 2 hours to 3 hours. This step is to obtain a final agitator to the compound of formula 5 is produced from the compound of formula (4) starting material.
  • the purification step may comprise a filtration step of filtering the stirred material, an extraction step, a concentration step and a drying step. Through such a purification step, a more pure compound of formula 5 may be prepared.
  • the filtration step it is possible to obtain a filtrate by filtering the stirring.
  • the agitated material is filtered by filter paper, a filtrate is obtained, and the filtered solid can be wash
  • the washed water may be subjected to an extraction step of extracting with a solvent.
  • the solvent is not limited to this as long as it is a nonpolar solvent, but may be, for example, dimethylformamide, dichloromethane, benzene, toluene, methane tetrachloride, ethyl ether, isopropyl ether and / or dimethyl sulfoxide and the like.
  • the concentration step by removing the solvent with a rotary concentrator, it can be concentrated to obtain a concentrate.
  • the filtrate and the concentrate of the filtration step may be subjected to a drying step of drying together.
  • the compound of Formula 5 can be prepared in large quantities up to 500 g-5000 g at a time.
  • Step (C) is a step of decarboxylation of the compound of Formula 5 by heating up to a temperature of 80 to 300 degrees Celsius without a solvent.
  • the step (C) may be a compound of formula 6 from the compound of formula 5 through a heating step.
  • the heating step only the compound of Formula 5 may be heated for 80 hours to 300 degrees Celsius, preferably 160 degrees to 240 degrees Celsius without a specific solvent, and may be performed for 6 hours to 48 hours.
  • the present invention is not limited thereto.
  • This step is to obtain a final product, the compound of formula 6 is produced from the compound of formula (5).
  • compounds of formula 6 can be prepared in large quantities up to 500 g-5000 g at a time.
  • a first embodiment to a fourth embodiment which are specific steps of each step included in the manufacturing method of an embodiment of the present invention.
  • the first embodiment shows in detail an example of preparing the starting material of the second embodiment.
  • a 250 ml two-necked flask is equipped with a thermometer and a dropping funnel and cooled with ice water (minus 10 degrees to 0 degrees Celsius).
  • Into the flask add 30 ml of anhydrous methanol and 0.8 g of chopped metal sodium, and cut off with nitrogen.
  • ethyl 2-chloroacrylate (Sigma-Aldrich Co., USA) was slowly added dropwise into a funnel of a dissolved solution in 20 ml of methanol.
  • Methanol in the agitate is concentrated by volatilization and acidified to pH 2 with 4N hydrochloric acid.
  • the acidified reactant was diluted with dichloromethane and extracted three times with 30 ml each.
  • the organic solvent layer was collected and washed three times with water.
  • the organic solvent layer is separated, anhydrous magnesium sulfate is added and left to dry for about 20 minutes. Thereafter, the anhydrous magnesium sulfate solid was filtered off and concentrated by removing the organic solvent from the residue with a rotary concentrator.
  • a yellow oil was obtained.
  • a 250 ml three-necked flask is equipped with a thermometer and a cooler. 1.38 g of methyl 3-hydroxythiophene-2-carboxylate is added to the flask at room temperature (18-25 ° C.) and dissolved in 20 ml of dimethylformamide.
  • a 2000 ml three-necked flask was equipped with a stirrer, thermometer and dropping funnel and cooled with ice water. To the flask is added 1500 ml methanol and 100 g of 3- (carboxymethoxy) thiophene-2-carboxylic acid. At this time, the temperature is maintained at 4 degrees Celsius.
  • TLC confirms that the reaction proceeded completely and filters with filter paper.
  • the filtered solid is washed five times with about 20-30 ml of water and dried in infrared for one day.
  • the filtrate is placed in a 2000 ml flask, the solvent is concentrated, filtered, and the solid is washed five times with about 100 ml of water and dried in infrared for 1 day.
  • the washed water layers are collected, extracted with dichloromethane, concentrated, and the solid is washed five times with about 100 ml of water and dried in infrared for 1 day.
  • reaction temperature rose to 230 degrees Celsius and then dropped back to 165-168 degrees Celsius.
  • the present invention has industrial applicability.

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)

Abstract

La présente invention concerne un nouveau procédé de préparation d'un dérivé de 3-alcoxy-thiophène qui présente l'avantage de produire le dérivé de 3-alcoxy-thiophène en masse à un rendement élevé.
PCT/KR2015/002962 2015-03-26 2015-03-26 Nouveau procédé de préparation d'un dérivé de 3-alcoxy-thiophène WO2016153094A1 (fr)

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* Cited by examiner, † Cited by third party
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CN114773327A (zh) * 2022-04-18 2022-07-22 广东优康精细化工有限公司 一种吡噻菌胺中间体的制备方法
CN114773327B (zh) * 2022-04-18 2023-08-18 广东优康精细化工有限公司 一种吡噻菌胺中间体的制备方法

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