CN113666860B - Preparation method of 7-ethyl tryptol - Google Patents

Preparation method of 7-ethyl tryptol Download PDF

Info

Publication number
CN113666860B
CN113666860B CN202010411678.4A CN202010411678A CN113666860B CN 113666860 B CN113666860 B CN 113666860B CN 202010411678 A CN202010411678 A CN 202010411678A CN 113666860 B CN113666860 B CN 113666860B
Authority
CN
China
Prior art keywords
ethyl
reaction
ethylene carbonate
temperature
preparation
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Active
Application number
CN202010411678.4A
Other languages
Chinese (zh)
Other versions
CN113666860A (en
Inventor
王亚青
鲍广龙
刘忠
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Lunan Pharmaceutical Group Corp
Original Assignee
Lunan Pharmaceutical Group Corp
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Lunan Pharmaceutical Group Corp filed Critical Lunan Pharmaceutical Group Corp
Priority to CN202010411678.4A priority Critical patent/CN113666860B/en
Publication of CN113666860A publication Critical patent/CN113666860A/en
Application granted granted Critical
Publication of CN113666860B publication Critical patent/CN113666860B/en
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
    • C07D209/04—Indoles; Hydrogenated indoles
    • C07D209/10—Indoles; Hydrogenated indoles with substituted hydrocarbon radicals attached to carbon atoms of the hetero ring
    • C07D209/12—Radicals substituted by oxygen atoms
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
    • Y02P20/00—Technologies relating to chemical industry
    • Y02P20/50—Improvements relating to the production of bulk chemicals
    • Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Indole Compounds (AREA)

Abstract

The invention belongs to the technical field of medicine synthesis, and particularly relates to a preparation method of 7-ethyl tryptol, which takes 7-ethyl indole as a raw material to react with ethylene carbonate under the action of alkali to synthesize 7-ethyl tryptol; the method has the advantages that the ethylene carbonate reagent product of the hydroxyethyl group is carbon dioxide, the method is clean and environment-friendly, the post-treatment is convenient, the method avoids the use of dangerous chemical reagents, the reaction is milder, the economy and the environment-friendly are realized, the yield is higher, and the method is suitable for industrial production.

Description

Preparation method of 7-ethyl tryptol
Technical Field
The invention belongs to the technical field of medicine synthesis, and particularly relates to a preparation method of 7-ethyl tryptol.
Background
Etodolac (Etodolac) is a powerful non-steroidal anti-inflammatory analgesic, is used for treating rheumatic arthritis, rheumatoid arthritis, osteoarthritis and other diseases, has the characteristics of good tolerance, light toxic and side effects, strong analgesic effect and the like, has few adverse reactions of gastrointestinal tracts, and is particularly suitable for old patients. The drug was developed by AHP Wyeth-Ayesrt company in the United states and was first marketed in the United kingdom in 1985, and has the following chemical structural formula:
7-ethyl tryptol is used as a key intermediate for synthesizing etodolac, directly influences the production, market supply and quality problems of the medicine, and has the following chemical structural formula:
the preparation methods reported at present for 7-ethyl color alcohol mainly comprise the following steps:
U.S. Pat. No. 5,172,72A 1 and the document "Synthesis of 7-ethyl-1H-indole", jiangsu chemical, 1993,21 (1), 17-19, 7-ethylindole, J.pharmaceutical & Chem., 1997,7 (1), 57-59, heteromycles, 2018,96 (1), 67-73 report that the by-product of the industrial production of p-nitroethylbenzene, namely chloramphenicol, or its downstream intermediate, is used as a raw material, reduced by tin powder/hydrochloric acid to give o-ethylaniline, then cyclized with chloral hydrate and hydroxylamine hydrochloride under acidic conditions to give an oximido acetamide derivative, then cyclized in concentrated sulfuric acid to give 7-ethylindolinone, then reduced with lithium aluminum hydride to give 7-ethylindole, finally reacted with oxalyl chloride, and then reduced by sodium borohydride to give the final product:
however, the process has the advantages of longer synthetic route, inconvenient operation, lower overall yield, higher risk of the used reducing agent and high price, and is not suitable for industrial production.
U.S. Pat. No.3,124A and literature "study of etodolac Synthesis Process" Tianjin chemical industry, 2004,18 (5), 22-23, edolac Synthesis Process "chemical theory, 2005,56 (8), 1536-1540 similarly uses o-nitroethylbenzene as raw material, and O-ethylaniline is obtained by reduction with iron powder, then diazotization reaction, reduction with sodium sulfite (sodium bisulfite or stannous chloride) to obtain o-ethylphenylhydrazine hydrochloride, and reflux reaction with 2, 3-dihydrofuran in 1, 4-dioxane to obtain the product:
the Fischer Indole synthesis method is a main flow process for producing 7-ethyl color alcohol at present, and is the synthesis method with the simplest process and the lowest production cost at present. The Fischer Indole synthesis appears to be a cleaner synthesis from the equation alone, but this is not actually the case for the synthesis of 7-ethyl tryptol, a technique which, on the one hand, requires the use of large amounts of non-environmentally or expensive organic solvents such as acetonitrile, DMF, DMAc, isobutanol, etc., and low solvent recovery; on the other hand, the Fischer rearrangement reaction needs strong acid catalysis to form indole ring, but the strong acid can also catalyze the indole ring to generate purple black sticky polymer through chain reaction, so that a plurality of impurities are generated, the crude product is low in purity, the post-treatment is complex, and the 7-ethyl color alcohol obtained through reaction separation is a dark (generally brownish black) sticky jelly or oily substance. The separation and purification method of this low-purity dark jelly is reported to be a silica gel column separation method (see U.S. Pat. No.3,124 and WO 9959970), an extraction separation method (see W02005002523), and the like. Although silica gel column chromatography can obtain 7-ethylchromanol as a high-purity product, the use of a large amount of solvent is uneconomical and impractical in industrial production. Although the extraction separation method is an effective method for improving the purity of industrial 7-ethyl color alcohol at present, the purity of the crude 7-ethyl color alcohol (the content is generally 60-85%) is still only 95-97% after separation and purification, and the color of the product is dark brown (see W02005002523) and still unsatisfactory.
In addition, as the system contains unreacted aldehyde (obtained by hydrolyzing 2, 3-dihydrofuran) and 2, 3-dihydrofuran after the indole is cyclized, the following three byproducts are easily generated, so that the crude product has low purity and complex post-treatment:
in addition, 2, 3-dihydrofuran with higher price is used in the process, so that the production cost is correspondingly increased.
Chinese patent application CN1740153A, CN1740154A and literature 7-New technology for synthesizing ethyl color alcohol, university chemical engineering report 2010,24 (1), 127-131 are prepared by hydrolyzing 2, 3-dihydrofuran under acidic condition to obtain 4-hydroxybutanal, reacting with o-ethyl phenylhydrazine salt to generate 4-hydroxybutanal o-ethyl phenylhydrazone, and finally Fischer cyclizing under concentrated sulfuric acid or glycol ether solvent, and vacuum distilling or recrystallizing with cyclohexane to obtain the target product:
however, the above process still has difficulty avoiding the drawbacks of the Fischer industry synthesis and the use of the more expensive 2, 3-dihydrofuran.
Similarly, chinese patent application CN107522649A and Chemical Engineering & processing: process Intensification,121 (2017) 144-148 adopt a tubular continuous flow reaction technology of microwave heating to react phenylhydrazine hydrochloride with 4-hydroxybutanal, thereby realizing continuous synthesis reaction of 7-ethylchromanol. Although the use of strong acids in the Fischer Indole synthesis is theoretically avoided, the process is of limited batch size and is not suitable for commercial scale-up.
Literature Heteroycles, 2003,60 (5) 1095-1110 uses 3-ethoxytetrahydrofuran, an active precursor of 2, 3-dihydrofuran, as a donor for 4-hydroxybutyraldehyde, which also inevitably results in higher production costs:
journal of Labelled Compounds and Radiopharmaceuticals, vol.XIV, no.3,1978,411-425, modified the strategy, was prepared by hydrolysis reduction after introduction of cyano group to 3-substituted-7 ethylindole:
however, the process uses the highly toxic KCN, has high operation risk, and the obtained cyano-substituted intermediate has 2-isomer impurities, so that the purity of the obtained product is low, and in addition, the carboxylic acid is reduced by using lithium aluminum hydride with high price and high risk, so that the operation safety is low, and the industrial large-scale production is difficult.
Furthermore, documents Journal of Medicinal Chemistry,1976,19 (3), 391-395 have designed and synthesized related indolinone derivatives using the Reformatsky reaction, but the process also requires the use of expensive and dangerous lithium aluminum hydride:
in addition, document Organic Syntheses, coll.vol.9, p.417 (1998); vol.74, p.248 (1997) first uses tert-butyldimethylchlorosilane (TMDMSCl) to protect 1-position indoline under the condition of n-butyllithium, then introduces bromine at 3-position through NBS, further carries out Li substitution under the condition of n-butyllithium, and then carries out nucleophilic substitution with propylene oxide, and deprotection to obtain related derivatives:
however, the process has the advantages of more synthesis steps, more complicated operation and lower overall yield; meanwhile, the method needs to be applied to the dangerous reagent n-butyl lithium which is in contact with water and carbon dioxide for spontaneous combustion, is heated, is inflammable by open flame and needs ultralow-temperature operation for multiple times, so that the operation safety is low, and the industrial large-scale production is difficult.
In summary, the preparation method of 7-ethyl-primary-color alcohol has the following problems:
1. the process route is longer, the final product relates to decompression fractionation operation, and the operation is complicated, so that the overall yield is lower.
2. The method adopts the Fischer Indole synthesis method under the strong acid condition to prepare the target product, and the obtained product has more impurities, is difficult to purify and has lower yield.
3. The process needs to use a large amount of acetonitrile, DMF, DMAc, isobutanol and other solvents which are not environment-friendly or expensive, and the recovery rate of the solvents is low.
4. The process adopts lithium aluminum hydride with higher risk and the highly toxic KCN, so that the operation safety is lower.
5.2, 3-dihydrofuran or 3-ethoxytetrahydrofuran which is an active precursor of 2, 3-dihydrofuran with a relatively high price is adopted as a donor of 4-hydroxybutyraldehyde, so that the problem of high production cost is caused.
In summary, the existing preparation method of 7-ethyl tryptophane has many defects in the aspects of safe process, complicated operation, low yield, higher production cost and the like, so that the research and the search of a reaction route which is mild in reaction condition, simple and convenient in operation process, high in product yield and purity and low in production cost and is suitable for industrialized production of 7-ethyl tryptophane still need to be solved.
Disclosure of Invention
Aiming at the problems of the existing 7-ethyl color alcohol preparation technology, the invention provides a novel preparation method of 7-ethyl color alcohol. The method has mild reaction conditions and simple operation process, and the prepared target product has higher purity and yield.
The specific technical scheme of the invention is as follows:
the preparation method of the 7-ethyl color alcohol specifically comprises the following steps:
and (3) adding 7-ethylindole and alkali into a reaction solvent at room temperature, adding ethylene carbonate at a controlled temperature, and after the addition, controlling the temperature until the reaction is finished, and performing post-treatment to obtain a target product.
Preferably, the alkali is selected from one or a combination of potassium carbonate, sodium bicarbonate, triethylamine, N, N-diisopropylethylamine and pyridine; among them, potassium carbonate is particularly preferred.
Preferably, the reaction solvent is one or a combination of benzene, toluene, xylene, N-dimethylformamide, 1, 4-dioxane, dimethyl sulfoxide and N-methylpyrrolidone, wherein N, N-dimethylformamide is particularly preferred.
In a preferred scheme, the feeding mole ratio of the 7-ethylindole to the alkali to the ethylene carbonate is 1:1.0 to 2.0:1.5 to 3.0, preferably 1:1.2:2.2.
preferably, the temperature of the ethylene carbonate is controlled to be 0-30 ℃; the reaction temperature is 90-120 ℃.
Preferably, the post-treatment steps are as follows: cooling the reaction solution to room temperature, filtering, adding methylene dichloride into the filtrate to extract and separate an organic phase, washing the organic phase by saturated saline water, drying by anhydrous sodium sulfate, filtering, and concentrating the filtrate under reduced pressure until the filtrate is dried to obtain the target product.
The invention has the beneficial effects that:
1. the invention provides a new preparation method of 7-ethyl primary color alcohol, which is prepared by taking 7-ethyl Indole as a starting material and ethylene carbonate under an alkaline condition, so that the problems of high production cost and more impurities, difficult purification and low yield of a product obtained by preparing a target product through a Fischer Indole synthesis method due to the adoption of 2, 3-dihydrofuran or an active precursor 3-ethoxytetrahydrofuran thereof as a donor of 4-hydroxy butyraldehyde are avoided;
2. meanwhile, the use of lithium aluminum hydride and the highly toxic KCN with higher risk is effectively avoided, the operation safety is improved, the target product does not need to be subjected to decompression fractionation operation and purification, and the production operation is simplified;
3. the ethylene carbonate reagent product with the hydroxyethyl group is carbon dioxide, so that the method is clean and environment-friendly and is convenient for post-treatment;
4. compared with the prior art, the preparation process of the 7-ethyl primary alcohol shortens the process route, is simple and convenient to operate and safe, and is more suitable for industrial production.
Detailed Description
The invention is further illustrated by the following examples, with the understanding that: the examples of the present invention are intended to be illustrative of the invention and not to be limiting of the invention, so that simple modifications to the invention which are based on the method of the invention are within the scope of the invention as claimed.
The structure of the 7-ethylchromanol compound obtained by the invention is confirmed as follows:
ESI-HRMS(m/z)：190.1234[M+H] + ； 1 H NMR(400MHz,CDCl 3 )δ8.05(br s,1H),7.50(d,J＝8.0Hz,1H),7.15-7.07(m,3H),3.92(t,J＝6.5Hz,2H),3.05(t,J＝6.0Hz,2H),2.87(q,J 1 ＝8.0Hz,J 2 ＝15.5Hz,J 3 ＝23.0Hz,2H)，1.38(t,J＝7.8Hz,3H)； 13 C NMR(100MHz,CDCl 3 )δ136.05,127.83,126.16,122.02,119.94,119.30,116.06,112.40,62.34,29.58,24.40,13.63.
in the following examples, various processes and methods, which are not described in detail, are conventional methods well known in the art.
Example 1
7-ethylindole (14.52 g,0.1 mol), potassium carbonate (16.58 g,0.12 mol) and N, N-dimethylformamide (150 ml) are added at the room temperature, ethylene carbonate (19.37 g,0.22 mol) is added at the temperature of 10-15 ℃, after the addition is finished, the temperature is controlled at 110-115 ℃ until the reaction is finished, the reaction solution is cooled to room temperature and filtered, methylene dichloride (100 ml) is added into the filtrate, an organic phase is taken out after the separation, the organic phase is washed by saturated saline (100 ml multiplied by 2), dried by anhydrous sodium sulfate and filtered, the filtrate is concentrated to dryness under reduced pressure, and the target product is obtained, the yield is 98.7%, and the HPLC purity is 99.92%.
Example 2
7-ethylindole (14.52 g,0.1 mol), potassium carbonate (13.82 g,0.1 mol) and ethylene carbonate (19.37 g,0.22 mol) are added into 1.4-dioxane (150 ml) at the temperature of 0-5 ℃, ethylene carbonate (19.37 g,0.22 mol) is added after the addition, the temperature is controlled to 90-100 ℃ until the reaction is finished, the reaction solution is cooled to room temperature and filtered, methylene dichloride (100 ml) is added into the filtrate, an organic phase is separated, the organic phase is washed by saturated saline (100 ml multiplied by 2), dried by anhydrous sodium sulfate, filtered and the filtrate is concentrated to dryness under reduced pressure, thus obtaining the target product, the yield is 94.6%, and the HPLC purity is 99.86%.
Example 3
7-ethylindole (14.52 g,0.1 mol), potassium carbonate (27.64 g,0.2 mol) and ethylene carbonate (19.37 g,0.22 mol) are added into dimethylbenzene (150 ml) at the temperature of 25-30 ℃, after the addition, the temperature is controlled to 115-120 ℃ until the reaction is finished, the reaction solution is cooled to room temperature and filtered, dichloromethane (100 ml) is added into filtrate, an organic phase is taken out from the filtrate, the organic phase is washed by saturated saline (100 ml multiplied by 2), anhydrous sodium sulfate is dried and filtered, the filtrate is concentrated to dryness under reduced pressure, and the target product is obtained, the yield is 93.9%, and the HPLC purity is 99.76%.
Example 4
7-ethylindole (14.52 g,0.1 mol), potassium carbonate (34.56 g,0.25 mol) and ethylene carbonate (19.37 g,0.22 mol) are added into toluene (150 ml) at the temperature of-5-0 ℃, after the addition, the temperature is controlled to be 85-90 ℃ until the reaction is finished, the reaction solution is cooled to room temperature and filtered, methylene dichloride (100 ml) is added into filtrate, an organic phase is taken out from the filtrate, the organic phase is washed by saturated saline (100 ml multiplied by 2), anhydrous sodium sulfate is dried and filtered, the filtrate is concentrated to dryness under reduced pressure, and the target product is obtained, the yield is 86.9%, and the HPLC purity is 99.65%.
Example 5
7-ethylindole (14.52 g,0.1 mol), sodium bicarbonate (10.08 g,0.12 mol) and paraxylene (150 ml) are added at room temperature, ethylene carbonate (13.21 g,0.15 mol) is added at the temperature of 10-15 ℃, after the addition is finished, the temperature is controlled at 110-115 ℃ until the reaction is finished, the reaction solution is cooled to room temperature and filtered, dichloromethane (100 ml) is added into the filtrate, an organic phase is separated, the organic phase is washed by saturated saline (100 ml multiplied by 2), anhydrous sodium sulfate is dried and filtered, the filtrate is concentrated to dryness under reduced pressure, and the target product is obtained, and the yield is 95.5% and the HPLC purity is 99.88%.
Example 6
7-ethylindole (14.52 g,0.1 mol), triethylamine (12.14 g,0.12 mol) and dimethyl sulfoxide (150 ml) are added at room temperature, ethylene carbonate (26.42 g,0.3 mol) is added at the temperature of 10-15 ℃, after the addition is finished, the temperature is controlled at 110-115 ℃ until the reaction is finished, the reaction solution is cooled to room temperature, the filtration is carried out, dichloromethane (100 ml) is added into the filtrate, an organic phase is taken out by separating the solution, the organic phase is washed by saturated saline (100 ml multiplied by 2), anhydrous sodium sulfate is dried, the filtration is carried out, the filtrate is concentrated to dryness under reduced pressure, and the target product is obtained, the yield is 93.7%, and the HPLC purity is 99.78%.
Example 7
7-ethylindole (14.52 g,0.1 mol), N-diisopropylethylamine (15.51 g,0.12 mol) and N-methylpyrrolidone (150 ml) are added at room temperature, ethylene carbonate (8.81 g,0.1 mol) is added at a temperature of 10-15 ℃, after the addition is completed, the temperature is controlled at 110-115 ℃ until the reaction is finished, the reaction solution is cooled to room temperature and filtered, dichloromethane (100 ml) is added into the filtrate, an organic phase is separated, the organic phase is washed by saturated saline (100 ml multiplied by 2), dried by anhydrous sodium sulfate, filtered, and the filtrate is concentrated to dryness under reduced pressure, thus obtaining the target product with 86.6 percent of yield and 99.66 percent of HPLC purity.
Example 8
7-ethylindole (14.52 g,0.1 mol), pyridine (9.50 g,0.12 mol) are added into N-methylpyrrolidone (150 ml), ethylene carbonate (30.82 g,0.35 mol) is added at the temperature of 10-15 ℃, after the addition is finished, the temperature is controlled at 120-125 ℃, the reaction solution is cooled to room temperature and filtered, methylene dichloride (100 ml) is added into the filtrate, an organic phase is taken out through separation, the organic phase is washed by saturated saline (100 ml multiplied by 2), anhydrous sodium sulfate is dried and filtered, the filtrate is concentrated to be dry under reduced pressure, and the target product is obtained, the yield is 85.2%, and the HPLC purity is 99.64%.

Claims (2)

1. The preparation method of 7-ethyl color alcohol is characterized in that 7-ethyl indole reacts with ethylene carbonate under the action of alkali to obtain 7-ethyl color alcohol, and the preparation method comprises the following steps: adding 7-ethylindole and alkali into a reaction solvent at room temperature, adding ethylene carbonate at a controlled temperature, and after the addition, controlling the temperature until the reaction is finished, and performing post-treatment to obtain a target product, wherein the synthetic route is as follows:
the alkali is selected from potassium carbonate, sodium bicarbonate and triethylamine,N,N-one or a combination of diisopropylethylamine, pyridine;
the reaction solvent is benzene, toluene, xylene,N,N-dimethylformamide, 1, 4-dioxane, dimethyl sulfoxide,N-one of methyl pyrrolidone or a combination thereof;
the temperature of the added ethylene carbonate is 0-30 ℃;
the reaction temperature is 90-120 ℃.
2. The preparation method according to claim 1, wherein the feeding molar ratio of the 7-ethylindole to the alkali to the ethylene carbonate is 1:1.0 to 2.0:1.5 to 3.0.
CN202010411678.4A 2020-05-14 2020-05-14 Preparation method of 7-ethyl tryptol Active CN113666860B (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN202010411678.4A CN113666860B (en) 2020-05-14 2020-05-14 Preparation method of 7-ethyl tryptol

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN202010411678.4A CN113666860B (en) 2020-05-14 2020-05-14 Preparation method of 7-ethyl tryptol

Publications (2)

Publication Number Publication Date
CN113666860A CN113666860A (en) 2021-11-19
CN113666860B true CN113666860B (en) 2024-03-15

Family

ID=78537551

Family Applications (1)

Application Number Title Priority Date Filing Date
CN202010411678.4A Active CN113666860B (en) 2020-05-14 2020-05-14 Preparation method of 7-ethyl tryptol

Country Status (1)

Country Link
CN (1) CN113666860B (en)

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN115650898A (en) * 2022-09-13 2023-01-31 华南理工大学 Synthesis method of 2-substituted 7-methoxy-tryptophol derivative

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1740153A (en) * 2005-08-23 2006-03-01 杭州科本化工有限公司 Prepn process of 7-ethyl tryptophol
CN1740154A (en) * 2005-08-23 2006-03-01 杭州科本化工有限公司 Prepn process of 7-ethyl tryptophol
CN105829288A (en) * 2013-12-19 2016-08-03 埃科特莱茵药品有限公司 Antibacterial 1h-indazole and 1h-indole derivatives
CN107522649A (en) * 2017-08-08 2017-12-29 衢州学院 A kind of 7 ethyl tryptophol method for continuously synthesizing of microwave assisted
KR20190081250A (en) * 2017-12-29 2019-07-09 아크로마코리아 주식회사 The preparing method of disperse orange dye

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1740153A (en) * 2005-08-23 2006-03-01 杭州科本化工有限公司 Prepn process of 7-ethyl tryptophol
CN1740154A (en) * 2005-08-23 2006-03-01 杭州科本化工有限公司 Prepn process of 7-ethyl tryptophol
CN105829288A (en) * 2013-12-19 2016-08-03 埃科特莱茵药品有限公司 Antibacterial 1h-indazole and 1h-indole derivatives
CN107522649A (en) * 2017-08-08 2017-12-29 衢州学院 A kind of 7 ethyl tryptophol method for continuously synthesizing of microwave assisted
KR20190081250A (en) * 2017-12-29 2019-07-09 아크로마코리아 주식회사 The preparing method of disperse orange dye

Non-Patent Citations (4)

* Cited by examiner, † Cited by third party
Title
7-乙基色醇的合成新工艺;吕延文，等;《高校化学工程学报》;第24卷(第1期);127-131 *
A versatile synthetic methodology for the synthesis of tryptophols;Simon J. Garden，等;《Tetrahedron》;第58卷;8399-8412 *
Hydroxyalkylation of indole with cyclic carbonates catalyzed by ionic liquids;GAO Guohua，等;《Chinese Journal of Catalysis》;第34卷(第6期);1187-1191 *
Paul M Wood，等.Bicyclic derivatives of the potent dual aromatase-steroid sulfatase inhibitor 2-bromo-4- {[(4-cyanophenyl)(4h-1,2,4-triazol-4-yl)amino] methyl} phenylsulfamate: synthesis, SAR, crystal structure, and in vitro and in vivo activities.《ChemMedChem》.2010,第5卷(第9期),1577-1593. *

Also Published As

Publication number Publication date
CN113666860A (en) 2021-11-19

Similar Documents

Publication Publication Date Title
CN102627573B (en) Synthesis method for 5-aminolevulinic acid hydrochloride
WO2017096996A1 (en) Preparation method for cobimetinib
CN114634441B (en) Method for synthesizing 6, 6-dimethyl-3-azabicyclo [3,1,0] hexane
CN113666860B (en) Preparation method of 7-ethyl tryptol
CN110790721B (en) Synthetic method of ceftazidime side chain ethyl ester
CN110305018B (en) Preparation method of 3-bromo-2-fluoronitrobenzene
CN105968040B (en) A kind of preparation method of Lei Dipawei intermediate
WO2016161826A1 (en) Method for preparing 4-isopropylamino-1-butanol
CN110684000B (en) Process for preparing benzofuran derivatives
CN112645833A (en) Synthesis method of (S) -2, 6-diamino-5-oxohexanoic acid
CN112225647A (en) Method for synthesizing 5-bromo-2-methoxyphenol
CN108101934B (en) Process for the preparation of trabectedin and intermediates thereof
CN112194548B (en) Alpha-amino-gamma-butyrolactone compound and preparation method thereof
CN111574463B (en) Rivastigmine intermediate compound IV
CN114437007A (en) Preparation method of prucalopride intermediate
CN113929612B (en) Preparation method of etodolac intermediate
CN111499528A (en) Terbutaline sulfate intermediate, preparation method thereof and method for preparing terbutaline sulfate by using terbutaline sulfate intermediate
CN108203396B (en) Synthesis of enkephalinase inhibitor
KR101856566B1 (en) New preparation method of 4'-Hydroxy-4-biphenylcarboxylic acid
CN114085161B (en) Intermediate for preparing 5-ALA-HCl and preparation method of 5-ALA-HCl
CN115504923A (en) Preparation method of 7-ethyl tryptophol
CN111171094B (en) Vanillin intermediate and preparation method and application thereof
CN115232054A (en) 7-ethyl tryptophol intermediate compound
CN114656401A (en) Method for preparing 4-chloropyridine-2-methyl formate serving as sorafenib key intermediate and suitable for industrial production
CN108503583B (en) Alkylation method of nitrogen-hydrogen-containing compound and application thereof

Legal Events

Date Code Title Description
PB01 Publication
PB01 Publication
SE01 Entry into force of request for substantive examination
SE01 Entry into force of request for substantive examination
GR01 Patent grant
GR01 Patent grant