CN113354530A - Method for preparing 4-acetyl-1-naphthoic acid - Google Patents

Method for preparing 4-acetyl-1-naphthoic acid Download PDF

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CN113354530A
CN113354530A CN202110254406.2A CN202110254406A CN113354530A CN 113354530 A CN113354530 A CN 113354530A CN 202110254406 A CN202110254406 A CN 202110254406A CN 113354530 A CN113354530 A CN 113354530A
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compound
acid
reaction
acetyl
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王仲清
李东明
陈永好
范炜隆
张梦辉
黄芳芳
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Dongguan Dongguan Sunshine Animal Health Pharmaceutical Co ltd
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C51/00—Preparation of carboxylic acids or their salts, halides or anhydrides
    • C07C51/347—Preparation of carboxylic acids or their salts, halides or anhydrides by reactions not involving formation of carboxyl groups
    • C07C51/377—Preparation of carboxylic acids or their salts, halides or anhydrides by reactions not involving formation of carboxyl groups by splitting-off hydrogen or functional groups; by hydrogenolysis of functional groups
    • C07C51/38—Preparation of carboxylic acids or their salts, halides or anhydrides by reactions not involving formation of carboxyl groups by splitting-off hydrogen or functional groups; by hydrogenolysis of functional groups by decarboxylation
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C67/00—Preparation of carboxylic acid esters
    • C07C67/08—Preparation of carboxylic acid esters by reacting carboxylic acids or symmetrical anhydrides with the hydroxy or O-metal group of organic compounds
    • 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
    • C07C67/313—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group by introduction of doubly bound oxygen containing functional groups, e.g. carboxyl groups
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    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D319/00—Heterocyclic compounds containing six-membered rings having two oxygen atoms as the only ring hetero atoms
    • C07D319/04—1,3-Dioxanes; Hydrogenated 1,3-dioxanes
    • C07D319/06—1,3-Dioxanes; Hydrogenated 1,3-dioxanes not condensed with other rings

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Abstract

The invention relates to a method for preparing 4-acetyl-1-naphthoic acid, and belongs to the technical field of pharmacy. The method provided by the invention takes cheap and easily-obtained 1, 4-naphthalene dicarboxylic acid as a raw material, and the 4-acetyl-1-naphthoic acid is prepared by decarboxylation after the addition of the Meldrum's acid, formylation of carboxyl and final hydrolysis. The method provided by the invention can obtain a high-purity product, the process avoids using a flammable metal reagent, namely methyl zinc, the reaction condition is mild, the operation is simple, and the method is suitable for industrial large-scale production.

Description

Method for preparing 4-acetyl-1-naphthoic acid
Technical Field
The invention belongs to the technical field of pharmacy, and particularly relates to a method for preparing 4-acetyl-1-naphthoic acid.
Background
Aforana (Afoxolaner), CAS: 1093861-60-9, chemical name: 4- { (5R) -5- [ 3-chloro-5- (trifluoromethyl) phenyl]-5- (trifluoromethyl) -4, 5-dihydro-1, 2-oxazol-3-yl } -N- { 2-oxo-2- [ (2,2, 2-trifluoroethyl) amino]Ethyl naphthalene-1-carboxamide having the formula C26H17ClF9N3O3And the molecular weight is 625.87. The Aforana is a pet medicament and is mainly used as an oral in-vitro anthelmintic for dogs clinically.
The chemical structural formula of the Aforana is shown as the formula (I):
Figure BDA0002962810210000011
the 4-acetyl-1-naphthoic acid and the derivatives thereof are key intermediates for synthesizing the alfilana, and the chemical structural formula of the 4-acetyl-1-naphthoic acid is shown as a formula (II):
Figure BDA0002962810210000012
in the prior art, the preparation process of the alfilamide intermediate (formula II) is disclosed in patent documents AU2005319305 and ChemCATChem,9(16),3121-3124, wherein the method disclosed in AU2005319305 has the disadvantages of low product yield, use of dangerous reagent methyl zinc and need of anhydrous environment for partial post-treatment; the method disclosed by ChemCatchem,9(16),3121-3124 has the disadvantages of using a noble metal catalyst, palladium acetate and seven times equivalent of formic acid, high cost, low yield and unsuitability for scale-up production.
The invention provides a method for preparing an Aforana intermediate 4-acetyl-1-naphthoic acid (formula II), which has the advantages of cheap and easily-obtained raw materials, simple reaction steps, mild reaction conditions, environmental friendliness and suitability for industrial production.
Disclosure of Invention
The invention provides a method for preparing an Aforana intermediate 4-acetyl-1-naphthoic acid shown in a formula (II).
In one aspect, a process for preparing 4-acetyl-1-naphthoic acid, comprises: step (d): adding acid into a reaction solvent of the compound (6), and reacting at a certain temperature to prepare a compound (7), wherein the reaction formula is shown as the following formula:
Figure BDA0002962810210000021
in the step (d), the reaction solvent is one or a combination of toluene, xylene, benzene or ethylbenzene.
In the step (d), the acid is one or a combination of hydrochloric acid, hydrobromic acid, sulfuric acid or nitric acid.
In the step (d), the certain temperature is 60-120 ℃.
The 4-acetyl-1-naphthoic acid can be prepared by the hydrolysis reaction of the compound (7). The hydrolysis reaction may include: dissolving the compound (7) in toluene, adding water, NaOH and TBAB, stirring at 60-120 ℃ for reaction, after the reaction is finished, cooling the reaction liquid to room temperature, separating liquid, washing the water phase with toluene, slowly dripping HCl into the water phase until solid is completely separated out, performing suction filtration, and drying to obtain the 4-acetyl-1-naphthoic acid.
In one aspect, a process for preparing 4-acetyl-1-naphthoic acid, comprises: step (c): reacting a compound (4) or a salt thereof with a compound (5) in the presence of a reaction solvent, a catalyst, a base and a condensing agent at a certain temperature to obtain a compound (6), wherein the reaction formula is shown as the following formula:
Figure BDA0002962810210000022
in the step (c), the reaction solvent is at least one of DCM, dichloroethane, DMSO or DMF.
In step (c), the catalyst is at least one of DMAP, HOBt or 4-PPy.
In the step (c), the base is at least one of triethylamine or DIPEA.
In step (c), the condensing agent is at least one of EDCI, DCC, or CDI.
In the step (c), the certain temperature is-10 ℃ to 30 ℃.
In some embodiments, a method of making 4-acetyl-1-naphthoic acid, comprises: step (b): reacting the compound (2) with alkali in a reaction solvent to obtain a compound (3), carrying out post-treatment, and hydrolyzing the compound (3) under the action of acid to prepare a compound (4), wherein the reaction formula is shown as the following formula:
Figure BDA0002962810210000031
wherein the content of the first and second substances,
m is lithium, sodium or potassium ion;
the reaction solvent is one or the combination of DMF, toluene, methanol or benzene;
the alkali is one or the combination of KOH, lithium hydroxide, sodium methoxide, sodium ethoxide, potassium tert-butoxide or potassium carbonate;
the acid is one or the combination of hydrochloric acid, hydrobromic acid, sulfuric acid or nitric acid.
In some embodiments, in step (b), the post-treatment is extraction by adding water and toluene, collecting the organic phase, and removing the solvent.
In some embodiments, a process for preparing 4-acetyl-1-naphthoic acid, further comprises step (a): adding thionyl chloride into a reaction solvent of the compound (1), and reacting at a certain temperature to prepare a compound (2), wherein the reaction formula is shown as the following formula:
Figure BDA0002962810210000032
wherein the content of the first and second substances,
the reaction solvent is selected from at least one of methanol and ethanol;
the certain temperature is 60-90 ℃.
In some embodiments, a method of making 4-acetyl-1-naphthoic acid comprises any one of the foregoing steps (a), step (b), step (c), step (d), or any two of the steps, or any three of the steps, or four of the steps. In some embodiments, a method of making 4-acetyl-1-naphthoic acid comprises steps (c) and (d) as previously described.
In some embodiments, the method for preparing 4-acetyl-1-naphthoic acid comprises reacting compound (1) in a solvent under the condition of adding thionyl chloride to obtain compound (2), reacting compound (2) with a base in the reaction solvent to obtain compound (3), hydrolyzing compound (3) under the action of an acid to obtain compound (4), reacting compound (4) with compound (5) to obtain compound (6), and reacting compound (6) to obtain compound (7), wherein the reaction route is shown as the following formula:
Figure BDA0002962810210000041
the compound (7) is hydrolyzed to prepare the 4-acetyl-1-naphthoic acid.
In the foregoing process, in some embodiments, the reaction solvent is preferably DCM (dichloromethane) in step (c), facilitating the reaction and work-up operations.
Among the foregoing processes, in some embodiments, the catalyst is preferably DMAP in step (c).
Among the foregoing processes, in some embodiments, the condensing agent is preferably EDCI in step (c).
In the foregoing processes, in some embodiments, in step (c), the reaction temperature is from-10 ℃ to 0 ℃. In some embodiments, in step (c), the reaction temperature is from 0 ℃ to 30 ℃. In some embodiments, in step (c), the reaction temperature is from 20 ℃ to 30 ℃.
In the above process, in some embodiments, the compound (5) is charged in an amount of 1.0 to 1.5 moles, preferably in a range of 1.1 to 1.4 moles, and more preferably in an amount of 1.3 moles, per 1.0 mole of the compound (4) or a salt thereof in the step (c), which is advantageous for obtaining the product.
In the foregoing methods, in some embodiments, the reaction time in step (c) may be 2 hours to 10 hours. In some embodiments, the reaction time is 3 hours to 8 hours.
In the foregoing processes, in some embodiments, compound (6) is prepared by reacting compound (4) or a salt thereof with compound (5) in dichloromethane or dichloroethane in the presence of DMAP, triethylamine, EDCI at-10 ℃ to 40 ℃ in step (c).
In the foregoing processes, in some embodiments, compound (6) is prepared by reacting compound (4) or a salt thereof with compound (5) in dichloromethane in the presence of DMAP, triethylamine, EDCI at-10 ℃ to 40 ℃ in step (c).
In the foregoing process, in some embodiments, the reaction solvent in step (d) is preferably toluene, which facilitates the reaction and work-up operations.
Among the foregoing processes, in some embodiments, the acid is preferably hydrochloric acid in step (d).
In the foregoing processes, in some embodiments, the reaction is carried out at a temperature of from 60 ℃ to 120 ℃ in step (d). In some embodiments, in step (d), the reaction temperature is from 65 ℃ to 100 ℃. In some embodiments, in step (d), the reaction temperature is from 105 ℃ to 120 ℃. In some embodiments, in step (d), the reaction temperature is 100 ℃.
In the foregoing methods, in some embodiments, the reaction time in step (d) may be 8 hours to 24 hours. In some embodiments, the reaction time is 12 hours to 20 hours.
In some embodiments of the foregoing processes, compound (7) is prepared in step (d) by reacting compound (6) in toluene in the presence of hydrochloric or hydrobromic acid at 100 ℃.
In the foregoing processes, in some embodiments, compound (7) is prepared by reacting compound (6) in toluene in the presence of hydrochloric acid at 100 ℃ in step (d).
Among the foregoing processes, in some embodiments, the reaction solvent in step (b) is preferably DMF.
In the foregoing process, in some embodiments, the base in step (b) is preferably KOH (potassium hydroxide).
In the foregoing process, in some embodiments, the acid in step (b) is preferably hydrochloric acid.
In the foregoing processes, in some embodiments, in step (a), the reaction temperature is from 70 ℃ to 80 ℃. In some embodiments, in step (a), the reaction temperature is 75 ℃.
In the above process, in some embodiments, the charging amount of thionyl chloride in step (a) is 1.0 to 3.5 moles, preferably in the range of 1.5 to 3 moles, and more preferably 2 moles, per 1.0 mole of the compound (1), which is advantageous for obtaining the product.
In the foregoing methods, in some embodiments, in step (a), the reaction time is from 2 hours to 18 hours. In some embodiments, the reaction time is 5 hours to 6 hours.
In the foregoing methods, in some embodiments, in step (a), compound (1) is dissolved in methanol or ethanol, thionyl chloride is added to react at 60 ℃ to 90 ℃, and after the reaction is finished, compound (2) is obtained through post-treatment; the post-treatment adopts water and toluene for extraction, collects an organic phase and removes the solvent.
In the foregoing methods, in some embodiments, in step (a), compound (1) is dissolved in methanol, thionyl chloride is added to react at 60 ℃ to 90 ℃, and after the reaction is finished, compound (2) is obtained through post-treatment; the post-treatment adopts water and toluene for extraction, collects an organic phase and removes the solvent.
Detailed Description
In order to make the technical solutions of the present invention better understood by those skilled in the art, the following further discloses some non-limiting examples to further explain the present invention in detail.
The reagents used in the present invention are either commercially available or can be prepared by the methods described herein.
The invention can adopt TLC or HPLC to monitor the reaction degree of the raw materials, such as HPLC, and the reaction is finished when the peak area is less than 1.0 percent.
In the present invention, room temperature means 25. + -. 5 ℃.
In the present invention, DCM means dichloromethane.
In the present invention, DMAP means 4-dimethylaminopyridine.
In the present invention, EDCI means 1-ethyl- (3-dimethylaminopropyl) carbodiimide hydrochloride.
In the present invention, DCC means dicyclohexylcarbodiimide.
In the present invention, CDI means N, N' -carbonyldiimidazole.
In the present invention, THF means tetrahydrofuran.
In the present invention, KOH means potassium hydroxide.
In the present invention, SOCl2Refers to thionyl chloride.
In the present invention, NaOH means sodium hydroxide.
In the present invention, Et3N refers to triethylamine.
In the present invention, TBAB means tetrabutylammonium bromide.
In the present invention, HOBt means 1-hydroxybenzotriazole.
In the present invention, 4-PPy means 4-pyrrolidinylpyridine.
In the present invention, DIPEA refers to N, N' -diisopropylethylamine.
EXAMPLE 1 preparation of Compound (2)
Figure BDA0002962810210000061
A1000 mL round-bottomed flask was charged with compound (1), i.e., 1, 4-naphthalenedicarboxylic acid (80g, 370mmol) and methanol (560mL), cooled to 0 ℃ or below, and SOCl was slowly added dropwise with stirring2(92.4g, 777mmol), after the dropwise addition, the temperature is raised to 75 ℃, and the reflux reaction is carried out for 12 hours. After the reaction is finished, the temperature is reduced to room temperature, the reaction liquid is decompressed and concentrated to obtain a solid crude product, the crude product is dissolved in 300mL of toluene, and 150mL of 10% K is used2CO3Washing twice with (mass fraction), washing with 150mL of water, separating organic phase, and concentrating under reduced pressureObtaining a compound (2): 86.0g, yield 96% and purity 98.1%; and (3) detection:
1H NMR(400MHz,CDCl3)δ9.49–8.48(m,2H),8.09(s,2H),7.77–7.58(m,2H),4.03(s,6H).
EXAMPLE 2 preparation of Compound (2)
A1000 mL round-bottomed flask was charged with compound (1), i.e., 1, 4-naphthalenedicarboxylic acid (50g, 231mmol) and methanol (350mL), concentrated sulfuric acid (47.6g, 485.7mmol) was slowly added dropwise with stirring, and after completion of the addition, the temperature was raised to 75 ℃ to conduct a reflux reaction for 12 hours. After the reaction is finished, the temperature is reduced to room temperature, the reaction liquid is decompressed and concentrated to obtain a solid crude product, the crude product is dissolved in 400mL of toluene, and 100mL of 10% K is used2CO3Washing twice (mass fraction), washing with 150mL of water, separating out an organic phase, and concentrating under reduced pressure to obtain a compound (2): 53.0g, yield 93.8%, purity 95%.
EXAMPLE 3 preparation of Compound (2)
A250 mL round-bottom flask was charged with compound (1), i.e., 1, 4-naphthalenedicarboxylic acid (10g, 46.2mmol) and methanol (70mL), and concentrated hydrochloric acid (11.5mL, 138.6mmol) was slowly added dropwise with stirring, after completion of the addition, the temperature was raised to 75 ℃ and the reaction was refluxed for 12 hours. After the reaction is finished, the temperature is reduced to room temperature, the reaction liquid is decompressed and concentrated to obtain a solid crude product, the crude product is dissolved in 100mL of ethyl acetate, and 50mL of 10% K is used2CO3Washing twice (mass fraction), washing with 50mL of water, separating out an organic phase, and concentrating under reduced pressure to obtain a compound (2): 18.3g, yield 81.1% and purity 95.7%.
EXAMPLE 4 preparation of Compound (3) and Compound (4)
Figure BDA0002962810210000071
A1000 mL round bottom flask was charged with compound (2), dimethyl 1,4 naphthalene dicarboxylate (30g, 122.8mmol) and THF (120mL), stirred to dissolve the solid, KOH (11g, 196.5mmol) was added and reacted at room temperature for 6 h. After the reaction is finished, cooling the reaction solution to below 0 ℃, adding water (240mL), washing twice with toluene (240mL), separating liquid, slowly dropwise adding 4mol/l hydrochloric acid (50mL) into the water phase at 0 ℃, and after dropwise adding, performing suction filtration to obtain 26.0g of off-white solid, namely the compound (4), wherein the yield is 92%, and the purity is 96.2%; and (3) detection:
1H NMR(400MHz,DMSO)δ8.93–8.68(m,1H),8.71–8.50(m,1H),8.21–7.97(m,2H),7.75–7.65(m,2H),3.95(s,3H).
EXAMPLE 5 preparation of Compound (6) and Compound (7)
Figure BDA0002962810210000072
A500 mL round-bottomed flask was charged with compound (4) i.e., 4-methoxycarbonyl-1-naphthoic acid (20g, 87mmol), compound (5) i.e., cyclopropanecarboxylic acid ring (methylene) isopropyl ester (16.3g, 113mmol) and dichloromethane (150mL), cooled to below 0 deg.C, and DMAP (6.3g, 52.2mmol) and Et were added with stirring3N (26.4g, 261mmol), after the solution is clear EDCI (33.4g, 174mmol) is added, stirring is continued at low temperature for 0.5h, then the temperature is raised to room temperature for reaction for 3h, and dichloromethane is removed by concentration under reduced pressure. Adding toluene (200mL) and 4mol/L HCl (100mL), heating to 65 deg.C, refluxing for 12h, separating, washing toluene phase with water (200mL), and adding 5% KHCO3(200mL), and concentrating the toluene phase under reduced pressure to obtain a white-like solid, i.e., a compound (7): 17.0g, yield 85%, purity 97.5%; and (3) detection:
1H NMR(400MHz,CDCl3)δ8.88-8.78(m,1H),8.55-8.45(m,1H),8.12(d,J＝7.5Hz,1H),7.81(d,J＝7.5Hz,1H),7.75–7.54(m,2H),4.03(s,3H),2.75(s,3H).
EXAMPLE 6 preparation of Compound (6) and Compound (7)
Adding a compound (4), namely 4-methoxycarbonyl-1-naphthoic acid (26g, 113mmol), a compound (5), namely malonic acid cyclo (ylidene) isopropyl ester (24.5g, 169.5mmol) and dichloromethane (260mL) into a 500mL round-bottom flask, cooling to below 0 ℃, adding DMAP (16.4g, 135.6mmol) under stirring, adding DCC (35.1g, 169.5mmol) after a solution is clear, continuing stirring at a low temperature for 0.5h, and raising the temperature to room temperature for reaction for 3 h. A large amount of DCU was removed by suction filtration, and the reaction solution was washed twice with clear water (200mL) and DCM was evaporated to dryness. Adding toluene (200mL) and 4mol/L HCl (100mL), heating to 65 ℃, refluxing for reaction for 12h, separating, washing a toluene phase with water (200mL), and concentrating the toluene phase under reduced pressure to obtain a yellow solid, namely a compound (7): 21.5g, yield 83.5% and purity 91.7%.
Example 7 preparation of 4-acetyl-1-naphthoic acid represented by formula (II)
Figure BDA0002962810210000081
A250 mL round-bottomed flask was charged with compound (7), i.e., methyl 4-acetyl-1-naphthoate (17g, 74.5mmol) and toluene (170mL), and the mixture was dissolved with stirring, and water (170mL), NaOH (5.9g, 149mmol) and TBAB (4.8g, 14.9mmol) were added thereto, and the mixture was allowed to warm to 65 ℃ for reaction overnight, the reaction mixture was cooled to room temperature, and the mixture was separated, and the aqueous phase was washed with toluene (170 mL). And (3) slowly dripping 4mol/L HCl (40mL) into the water phase under the stirring at room temperature until the solid is completely separated out, continuously stirring for 1h, performing suction filtration, and drying to obtain a white-like solid, namely 4-acetyl-1-naphthoic acid: 14.5g, yield 91.2% and purity 98.6%; and (3) detection:
1H NMR(400MHz,DMSO)δ8.76(dd,J＝7.2,2.3Hz,1H),8.43(dd,J＝7.2,2.3Hz,1H),8.07(dd,J＝20.6,7.5Hz,2H),7.75–7.60(m,2H),2.72(s,3H).
in conclusion, the method for preparing the alfilana intermediate (formula II) provided by the invention has the advantages of cheap and easily available raw materials, simple reaction steps, mild reaction conditions, environmental friendliness, suitability for industrial production and the like. Compared with the prior art, the Aforana intermediate (formula II) obtained by the method has the advantages of high purity and high yield.
While the methods of the present invention have been described in terms of preferred embodiments, it will be apparent to those of ordinary skill in the art that variations and modifications of the methods and applications described herein, as well as other suitable variations and combinations, may be made to implement and use the techniques of the present invention within the context, spirit and scope of the invention. Those skilled in the art can modify the process parameters appropriately to achieve the desired results with reference to the disclosure herein. It is expressly intended that all such similar substitutes and modifications which would be obvious to those skilled in the art are deemed to be included within the invention.

Claims (10)

1. A process for preparing 4-acetyl-1-naphthoic acid comprising:
step (c): reacting a compound (4) or a salt thereof with a compound (5) in the presence of a reaction solvent, a catalyst, a base and a condensing agent at a certain temperature to obtain a compound (6), wherein the reaction formula is shown as the following formula:
Figure FDA0002962810200000011
wherein the content of the first and second substances,
the catalyst is at least one of DMAP, HOBt or 4-PPy;
the condensing agent is at least one of EDCI, DCC or CDI; and/or
Step (d): in a reaction solvent, reacting a compound (6) under the conditions of adding acid and a certain temperature to prepare a compound (7), wherein the reaction formula is shown as the following formula:
Figure FDA0002962810200000012
wherein the content of the first and second substances,
the acid is at least one of hydrochloric acid, hydrobromic acid, sulfuric acid or nitric acid.
2. The process for producing 4-acetyl-1-naphthoic acid according to claim 1, further comprising, step (a): adding thionyl chloride into a reaction solvent of the compound (1), and reacting at a certain temperature to prepare a compound (2), wherein the reaction formula is shown as the following formula:
Figure FDA0002962810200000013
wherein the content of the first and second substances,
the reaction solvent is at least one of methanol or ethanol;
the certain temperature is 60-90 ℃.
3. The process of claim 1 or 2, step (c), the reaction solvent is at least one of DCM, dichloroethane, DMSO, or DMF; or in the step (d), the reaction solvent is at least one of toluene, xylene, benzene or ethylbenzene.
4. The method of claim 1 or 2, wherein in step (c), the certain temperature is between-10 ℃ and 30 ℃; or in the step (d), the certain temperature is 60-90 ℃.
5. The process of claim 1 or 2, wherein in step (c), the base is at least one of triethylamine or DIPEA.
6. The process according to claim 1 or 2, wherein the compound (5) is charged in an amount of 1.0 to 1.5 mol per 1.0 mol of the compound (4) or a salt thereof in the step (c).
7. The process of claim 2, wherein the amount of thionyl chloride charged in step (a) is 1.0 to 3.5 moles per 1.0 mole of the compound (1).
8. The method of claim 1 or 2, further comprising: step (b): reacting the compound (2) with alkali in a reaction solvent to obtain a compound (3), carrying out post-treatment, and hydrolyzing the compound (3) under the action of acid to prepare a compound (4), wherein the reaction formula is shown as the following formula:
Figure FDA0002962810200000021
wherein the content of the first and second substances,
m is lithium, sodium or potassium ion;
the reaction solvent is at least one of DMF, toluene, methanol or benzene,
the alkali is at least one of KOH, LiOH, sodium hydroxide, sodium methoxide, sodium ethoxide, potassium tert-butoxide or potassium carbonate,
the acid is at least one of hydrochloric acid, hydrobromic acid, sulfuric acid or nitric acid.
9. The method of claim 1 or 2 or 8, further comprising: the compound (7) is hydrolyzed to prepare 4-acetyl-1-naphthoic acid
Figure FDA0002962810200000022
10. A compound of the formula:
Figure FDA0002962810200000023
CN202110254406.2A 2020-03-07 2021-03-05 Method for preparing 4-acetyl-1-naphthoic acid Pending CN113354530A (en)

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN113866322A (en) * 2021-11-24 2021-12-31 丽珠集团新北江制药股份有限公司 Method for detecting Aforana intermediate by reversed-phase high performance liquid chromatography

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN113866322A (en) * 2021-11-24 2021-12-31 丽珠集团新北江制药股份有限公司 Method for detecting Aforana intermediate by reversed-phase high performance liquid chromatography
CN113866322B (en) * 2021-11-24 2023-05-23 丽珠集团新北江制药股份有限公司 Method for detecting aforana intermediate by reversed-phase high performance liquid chromatography

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