CN107721842A - A kind of method for preparing 10,10 disubstituted 3 bromine anthrones - Google Patents
A kind of method for preparing 10,10 disubstituted 3 bromine anthrones Download PDFInfo
- Publication number
- CN107721842A CN107721842A CN201710973533.1A CN201710973533A CN107721842A CN 107721842 A CN107721842 A CN 107721842A CN 201710973533 A CN201710973533 A CN 201710973533A CN 107721842 A CN107721842 A CN 107721842A
- Authority
- CN
- China
- Prior art keywords
- reaction
- compound
- anthrones
- disubstituted
- bromines
- 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.)
- Granted
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C51/00—Preparation of carboxylic acids or their salts, halides or anhydrides
- C07C51/083—Preparation of carboxylic acids or their salts, halides or anhydrides from carboxylic acid anhydrides
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C29/00—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring
- C07C29/36—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring increasing the number of carbon atoms by reactions with formation of hydroxy groups, which may occur via intermediates being derivatives of hydroxy, e.g. O-metal
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C29/00—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring
- C07C29/60—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring by elimination of -OH groups, e.g. by dehydration
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
- C07C45/27—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by oxidation
- C07C45/29—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by oxidation of hydroxy groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
- C07C45/27—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by oxidation
- C07C45/29—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by oxidation of hydroxy groups
- C07C45/298—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by oxidation of hydroxy groups with manganese derivatives
-
- 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
- C07C51/367—Preparation of carboxylic acids or their salts, halides or anhydrides by reactions not involving formation of carboxyl groups by introduction of functional groups containing oxygen only in singly bound form
-
- 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
Abstract
The method that one kind prepares 10,10 disubstituted 3 bromine anthrones, belongs to organic chemistry filed.Using phthalic anhydride and bromobenzene as raw material, successively by ring-opening reaction, reduction reaction, esterification, tertiary alcoholization reaction, ring-closure reaction and oxidation reaction, 10,10 disubstituted 3 bromine anthrones are obtained.This method raw material is cheap and easy to get, and each reaction condition that walks is simple, good to tolerance containing bromo functional groups.
Description
Technical field
The invention discloses the preparation method of anthracene ketone compounds, and in particular to one kind prepares the disubstituted -3- bromines of 10,10-
The method of anthrone, belongs to organic chemistry filed.
Background technology
10,10- disubstituted anthrones are widely used in medicine synthesis and luminous organic material field, such as 10,10- dimethyl
Anthrone is the important intermediate for synthesizing antipsychotic class medicine melitracen hydrochloride；The disubstituted anthrone bromo derivatives of 10,10- are then
It is the important intermediate for synthesizing luminous organic material, its prepared luminous organic material has a good thermal stability, current efficiency,
With good industrialization prospect (referring to：Chinese Journal of Modern Applied Pharmacy magazine, 2009,26,125-126；CN106467497,
2016)。
The 10,10- dimethyl anthrone methods reported for work at present are as follows：
(1) o-chlorobenzyl chlorine mixes progress substitution reaction with benzene and adjacent chlorodiphenyl methane is made, then by adjacent chlorodiphenyl methane
Be made RMgBr through grignard reaction with magnesium rod, RMgBr with being made 10 through hydrolysis, condensation reaction after acetone addition reaction,
10- dimethyl diphenyl methanes, 10,10- dimethyl diphenyl methane illumination bromo, hydrolysis are finally obtained into 10,10- dimethyl
Anthrone (referring to：CN105061177,2015).
(2) anthrone is raw material, in the presence of highly basic, methylation reaction occurs with iodomethane and obtains 10,10- dimethylanthracenes
Ketone is, it is necessary to add expensive crown ether-like phase transfer catalysts, and with a large amount of methoxylation impurity, and due to being two-phase
System, experimental result poor repeatability (referring to：J.Chem.Res.,2001,113-115).
But the route of both the above synthesis 10,10- dimethyl anthrones, due to the reaction incompatible with bromine substituent be present
Condition, for example, grignard reaction, basic conditions, and it is inapplicable with preparing 10, the 10- disubstituted derivatives containing bromine substituent.
The content of the invention
In order to overcome problems of the prior art, the invention discloses one kind to prepare the disubstituted -3- bromines anthracenes of 10,10-
The method of ketone.Using phthalic anhydride and bromobenzene as raw material, by six reactions steps, it is followed successively by by ring-opening reaction, reduction reaction, esterification
Reaction, tertiary alcoholization reaction, ring-closure reaction and oxidation reaction, obtain the disubstituted -3- bromines anthrones of 10,10-.Pass through following reaction road
Line：
Further, in the above-mentioned technical solutions, the ring-opening reaction：With phthalic anhydride and bromobenzene raw material, deposited in alchlor
Under, single open loop generation 2- (4- benzoyl bromides) benzoic acid (compound 1) occurs.
Further, in the above-mentioned technical solutions, the reduction reaction：2- (4- benzoyl bromides) benzoic acid (compound
1) reacted with sodium borohydride, generate 2- ((4- bromophenyls) hydroxymethyl) benzoic acid (compound 2).
Further, in the above-mentioned technical solutions, the esterification：2- ((4- bromophenyls) hydroxymethyl) benzoic acid
(compound 2) is left in acid is reacted with methanol, generates 2- ((4- bromophenyls) hydroxymethyl) methyl benzoate (compound
3).During the course of the reaction, it is necessary to add the sulfuric acid of accelerator 80%, 80% sulfuric acid and 2- ((4- bromophenyls) hydroxymethyl) benzoic acid
The mol ratio of (compound 2) is 1:1.
Further, in the above-mentioned technical solutions, the tertiary alcoholization reaction, 2- ((4- bromophenyls) hydroxymethyl) benzoic acid
Methyl esters (compound 3) and grignard reagent reacting, generate the alcohol of 2- (2- ((4- bromophenyls) hydroxymethyl) phenyl) propyl- 2 or (2- ((4-
Bromophenyl) hydroxymethyl) phenyl) benzhydrol (compound 4).During the course of the reaction, it is necessary to add tetrahydrofuran and n-hexane
Make solvent, the weight ratio of tetrahydrofuran and n-hexane is 5:1.RMgBr is selected from methyl Grignard or phenyl grignard reagent,
Corresponding R is respectively methyl or phenyl.
Further, in the above-mentioned technical solutions, the ring-closure reaction：2- (2- ((4- bromophenyls) hydroxymethyl) phenyl)
The alcohol of propyl- 2 or (2- ((4- bromophenyls) hydroxymethyl) phenyl) benzhydrol (compound 4) leave reaction in lewis acid, generation
The bromo- 10,10- dimethyl -9,10- dihydroanthracenes -9- alcohol of 3- or the bromo- 10,10- diphenyl -9,10- dihydroanthracenes -9- alcohol (compounds of 3-
5).Lewis promoters are selected from Boron tribromide, boron trifluoride or triphenyl borine.During the course of the reaction, 2- (2- ((4- bromobenzenes
Base) hydroxymethyl) phenyl) propyl- 2 alcohol or (2- ((4- bromophenyls) hydroxymethyl) phenyl) benzhydrol (compound 4) and Louis
This sour accelerator solution needs to keep equal proportion while is added dropwise, and time for adding needs to control and needed in more than 2.0h, reaction kettle temperature
Control 10 DEG C of ＜.
Further, in the above-mentioned technical solutions, the oxidation reaction：Oxidation reaction occurs for compound 5, and generation 3- is bromo-
10,10- dimethyl anthrone or the bromo- 10,10- diphenyl anthrones (compound 6) of 3-.During the course of the reaction, it is necessary to add trifluoro second
Acid, accelerator is made with manganese dioxide, the mol ratio of compound 5, trifluoroacetic acid and manganese dioxide is 1:0.1:1.
The beneficial effects of the invention are as follows：Raw material is cheap and easy to get, and each reaction condition that walks is simple, to tolerance containing bromo functional groups
It is good.
Embodiment
With reference to embodiment, the invention will be further described.These embodiments be merely to illustrate the present invention rather than
Limit the scope of the present invention.
Embodiment 1
The preparation of the bromo- 10,10- dimethyl anthrones of 3-
The first step：
Phthalic anhydride 1192g, bromobenzene 10.10Kg are added in 30L chuck kettles, tri-chlorination is added portionwise under stirring
Aluminium 2202g, add the logical deep fat of rear chuck and be warming up to 90 DEG C, and insulated and stirred 3.5h.
Reaction solution is released from bottom valve while hot, is poured into the 60L open drums equipped with 25Kg frozen water, adds 36Wt.% hydrochloric acid
288g adjusts pH=1~2, then adds dichloroethanes 7.43Kg × 2 and extracts.
Merge oil reservoir, add the solution prepared using potassium carbonate 2.48Kg and water 15.00Kg, stir 0.5h, separate water layer
Kettle is returned, hydrochloric acid 3.905Kg (36Wt.%) regulations pH=1~2 are added portionwise under stirring, separate out a large amount of white solids.Take out
Filter, and eluted in three times with water 16.0Kg, wet cake is obtained, white powder 2167g, yield 89% are obtained after drying.
Second step：
Add ethanol 10Kg, 1 step product 936g in 30L chuck kettles, chuck lead to cooling oil be cooled to 0 DEG C it is stand-by.
Sodium borohydride 116g is added portionwise, 1.0h is added, and kettle temperature is controlled at 0-10 DEG C, is then turned off refrigeration and is to slowly warm up to
20-25 DEG C of insulation reaction 3.0h.
Reaction solution is poured slowly into the 60L open drums equipped with 10% hydrochloric acid 5.0Kg, stirs 20min, separates out a large amount of whites
Solid, then add dichloroethanes 5.0Kg × 2 and extract, merge oil reservoir, add water 10.0Kg × 2 to wash to water layer pH=6-7, institute
45 DEG C of oil reservoir revolving it is de- it is dry after scrape to pallet, naturally dry obtains pale powder 846g, yield 90% in fume hood.
3rd step：
Methanol 3530g, second step product 1692g are added in 30L chuck kettles, 80% sulfuric acid is added dropwise under mechanical agitation state
675g, 40min are dripped off.It is added dropwise, is warming up to backflow, and insulated and stirred 9.0h.
Reaction solution is transferred in the 60L open drums equipped with water 9.25Kg, stirring 30min, and addition dichloroethanes 9.246Kg ×
2 are extracted twice, and oil reservoir merges, and are washed using water 9.246Kg × 2.
Gained oil reservoir negative pressure is concentrated to give the residual 1688g of kettle, yield 95%.
4th step：
The 3rd step product 1668g, tetrahydrofuran 5052g, n-hexane 1010g are added into 30L chuck kettles, chuck leads to low temperature
Circulation fluid mechanical agitation be cooled to -4 DEG C it is stand-by.
Methyl-magnesium-chloride 5194mL (3.0M tetrahydrofuran solutions) is added dropwise using constant pressure funnel, 3.0h is dripped off, and is added dropwise
Process temperature is controlled at -4~2 DEG C.After being added dropwise, chuck stops logical low-temperature circulating liquid, and 14 DEG C are to slowly warm up to after 1.0h, with
14-16 DEG C of insulated and stirred 2.0h afterwards, kettle temperature are down to 5 DEG C, are discharged in 25L open drums.
Reaction solution is poured slowly into the 60L open drums equipped with 20% ammonium chloride 9904g, charging finishes stirring 0.5h, added
Dichloroethanes 9.90Kg × 2 extract.Merge oil reservoir, washed using water 9.90Kg × 2, washing finishes gained oil reservoir negative pressure concentration institute
Obtain the residual 1780g of kettle, yield 107%.
5th step：
Dichloromethane 4000g bottoming is added into 30L chuck kettles, chuck leads to sub-cooled circulation fluid mechanical agitation and is cooled to
0 DEG C stand-by.4th step product 1780g and Boron tribromide 1753g are dissolved in dichloromethane 5000g respectively, and are transferred to dropping liquid leakage
Struggle against stand-by.
The dichloromethane solution of the 4th step product of dropwise addition and Boron tribromide maintains the two equimolar ratio drop into kettle simultaneously
Add, 10 DEG C of control kettle temperature ＜, 2.0h is added dropwise, and drips off rear insulated and stirred 0.5h.
25L open drums are discharged to, is poured slowly into the 60L open drums equipped with 16.29Kg water and is quenched, separate oil reservoir, are added
Wash water 16.286Kg × 2.Gained oil reservoir, negative pressure are concentrated to give the residual 1544g of kettle, yield 92% after washing.
6th step：
Dichloromethane 10.02Kg, trifluoroacetic acid 58g, the 5th step product 1544g, chuck admittance heat are added in 30L chuck kettles
It is stand-by that oil is warming up to backflow.Manganese dioxide 442.7g solution is added portionwise, after 1.5h is added, continues the 4.0h that flows back.
Reaction solution recovers to room temperature, filters, and filter cake is eluted using dichloromethane 1.000Kg, filtrate, uses water
10.00Kg × 2 washings.
Gained oil reservoir is decolourized by the chromatographic column equipped with silica gel 500g after washing, and gained eluent, negative pressure is concentrated to give
To the residual 1503g of kettle, yield 98%.
Embodiment 2
The preparation of the bromo- 10,10- diphenyl anthrones of 3-
The first step, second step and the 3rd step are prepared with reference to example 3.
4th step：
The 3rd step product 55.6g is added into 1000mL four-hole bottles, tetrahydrofuran 150g, n-hexane 30g, is put into ice maker machine
Tool stirring be cooled to -4 DEG C it is stand-by.
Phenyl-magnesium-bromide 173mL (3.0M diethyl ether solutions) is added dropwise using constant pressure funnel, 3.0h is dripped off, and process temperature is added dropwise
Degree control is at -4~2 DEG C.After being added dropwise, reaction bulb is taken out from ice maker, 10.0h is stirred at room temperature.
Reaction solution is poured slowly into the measuring cup equipped with 20% ammonium chloride 500g and is quenched, dichloroethanes 500g × 2 is added and extracts
Take.Merge oil reservoir, washed using water 500g × 2, washing finishes the gained oil reservoir negative pressure concentration gained residual 66.5g of kettle, yield 86%.
5th step：
Into 1000mL four-hole bottles add dichloromethane 100g bottoming, be put into mechanical agitation in ice maker be cooled to 0 DEG C it is stand-by.
4th step product 66.5g and Eorontrifluoride etherate 37.8g are dissolved in dichloromethane 200g respectively, and are transferred to dropping funel and treat
With.
The dichloromethane solution of the 4th step product of dropwise addition and Boron tribromide maintains the two equimolar ratio drop into kettle simultaneously
Add, 10 DEG C of control kettle temperature ＜, 2.0h is added dropwise, and drips off rear insulated and stirred 0.5h.
Reaction solution is poured slowly into the measuring cup equipped with 1000g water and is quenched, and separates oil reservoir, adds water 1000g × 2 and washs.Wash
Gained oil reservoir, negative pressure are concentrated to give the residual 51g of kettle, yield 80% after washing.
6th step：
Dichloromethane 500g, trifluoroacetic acid 1.4g, 5 step product 51g are added in 1000mL four-hole bottles, oil bath is warming up to backflow
It is stand-by.Manganese dioxide 10.4g solution is added portionwise, after 0.5h is added, continues the 4.0h that flows back.
Reaction solution recovers to room temperature, filters, and filter cake is eluted using dichloromethane 200g, and filtrate is washed using water 500g × 2
Wash.
Gained oil reservoir is decolourized by the chromatographic column equipped with silica gel 50g after washing, and gained eluent, negative pressure is concentrated to give
The residual 48.2g of kettle, yield 95%.
Embodiment above describes the general principle of the present invention, main features and advantages.The technical staff of the industry should
Understand, the present invention is not limited to the above embodiments, the original for simply illustrating the present invention described in above-described embodiment and specification
Reason, under the scope for not departing from the principle of the invention, various changes and modifications of the present invention are possible, and these changes and improvements are each fallen within
In the scope of protection of the invention.
Claims (8)
1. the method that one kind prepares the disubstituted -3- bromines anthrones of 10,10-, it is characterised in that comprise the following steps：With phthalic anhydride and bromine
Benzene is raw material, successively by ring-opening reaction, reduction reaction, esterification, tertiary alcoholization reaction, ring-closure reaction and oxidation reaction, is obtained
To the disubstituted -3- bromines anthrones of 10,10-；Reaction equation is as follows：
2. the method for the disubstituted -3- bromines anthrones of 10,10- is prepared according to claim 1 one kind, it is characterised in that the open loop is anti-
Should：With phthalic anhydride and bromobenzene, left in alchlor, single open loop generation compound 1 occurs.
3. the method for the disubstituted -3- bromines anthrones of 10,10- is prepared according to claim 1 one kind, it is characterised in that the reduction is anti-
Should：Compound 1 is reacted with sodium borohydride, generates compound 2.
4. the method for the disubstituted -3- bromines anthrones of 10,10- is prepared according to claim 1 one kind, it is characterised in that the esterification is anti-
Should：Compound 2 is left in acid is reacted with methanol, generates compound 3；
During the course of the reaction, it is necessary to add the sulfuric acid of accelerator 80%, the mol ratio of 80% sulfuric acid and compound 2 is 1:1.
5. the method for the disubstituted -3- bromines anthrones of 10,10- is prepared according to claim 1 one kind, it is characterised in that the tertiary alcohol
Reaction：Compound 3 and grignard reagent reacting, generate compound 4；During the course of the reaction, it is necessary to add tetrahydrofuran and n-hexane
Make solvent, the weight ratio of tetrahydrofuran and n-hexane is 5:1.
6. the method for the disubstituted -3- bromines anthrones of 10,10- is prepared according to claim 5 one kind, it is characterised in that：The tertiary alcohol
In reaction, RMgBr is selected from methyl Grignard or phenyl grignard reagent, and corresponding R is respectively methyl or phenyl.
7. the method for the disubstituted -3- bromines anthrones of 10,10- is prepared according to claim 1 one kind, it is characterised in that the cyclization is anti-
Should：Compound 4 leaves carry out ring closure reaction in lewis acid, generates compound 5；Lewis acid is selected from Boron tribromide, borontrifluoride
Boron or triphenyl borine；During the course of the reaction, compound 4 and lewis acid solution need to keep equal proportion while are added dropwise, during dropwise addition
Between need control in more than 2.0h, reaction kettle temperature needs to control 10 DEG C of ＜.
8. the method for the disubstituted -3- bromines anthrones of 10,10- is prepared according to claim 1 one kind, it is characterised in that the oxidation is anti-
Should：Oxidation reaction occurs for compound 5, generates compound 6；During the course of the reaction, it is necessary to add trifluoroacetic acid, manganese dioxide is made to promote
Enter agent, the mol ratio of compound 5, trifluoroacetic acid and manganese dioxide is 1:0.1:1.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710973533.1A CN107721842B (en) | 2017-10-18 | 2017-10-18 | Method for preparing 10, 10-disubstituted-3-bromoanthrone |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710973533.1A CN107721842B (en) | 2017-10-18 | 2017-10-18 | Method for preparing 10, 10-disubstituted-3-bromoanthrone |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN107721842A true CN107721842A (en) | 2018-02-23 |
| CN107721842B CN107721842B (en) | 2020-05-26 |
Family
ID=61211941
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201710973533.1A Active CN107721842B (en) | 2017-10-18 | 2017-10-18 | Method for preparing 10, 10-disubstituted-3-bromoanthrone |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN107721842B (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN114685255A (en) * | 2020-12-30 | 2022-07-01 | 重庆圣华曦药业股份有限公司 | Preparation method of melitracen hydrochloride intermediate |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3177209A (en) * | 1960-09-16 | 1965-04-06 | Kefalas As | Dihydroanthracene compounds |
-
2017
- 2017-10-18 CN CN201710973533.1A patent/CN107721842B/en active Active
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3177209A (en) * | 1960-09-16 | 1965-04-06 | Kefalas As | Dihydroanthracene compounds |
Non-Patent Citations (2)
| Title |
|---|
| PAK-TONG LEUNG，DAVID Y. CURTIN: "Syntheses and nuclear magnetic resonance studies of some sterically hindered methylenedihydroanthracenes bearing methyl groups in the 1,8-aryl or methylene positions", 《JOURNAL OF THE AMERICAN CHEMICAL SOCIETY》 * |
| 张立颖 等: "盐酸美利曲辛合成工艺研究", 《山东化工》 * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN114685255A (en) * | 2020-12-30 | 2022-07-01 | 重庆圣华曦药业股份有限公司 | Preparation method of melitracen hydrochloride intermediate |
| CN114685255B (en) * | 2020-12-30 | 2023-12-26 | 重庆圣华曦药业股份有限公司 | Preparation method of melitracen hydrochloride intermediate |
Also Published As
| Publication number | Publication date |
|---|---|
| CN107721842B (en) | 2020-05-26 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN109721585B (en) | Preparation method of baroxavir key intermediate | |
| CN103965280B (en) | A kind of preparation method of fulvestrant intermediate | |
| CN108191621A (en) | A kind of preparation process of pinacoline | |
| CN102060867A (en) | Method for preparing potassium trifluoroborate series compounds | |
| CN106278850A (en) | The synthetic method of prothioconazoles intermediate 1 chlorine 1 acetylcyclopropane | |
| CN105820128B (en) | A kind of preparation method of cyproconazole | |
| CN107721842A (en) | A kind of method for preparing 10,10 disubstituted 3 bromine anthrones | |
| CN102741224B (en) | Method for producing astaxanthin dimethyl disuccinate | |
| CN106749139A (en) | One kind is polysubstituted to condense benzofuran derivative and preparation method thereof | |
| CN111635300A (en) | Method for preparing deuterated benzoin by using deuterium source as deuterium source | |
| CN105884581A (en) | Method for preparing 2-(1-methylethyl)-5-[(E)-2-phenylethenyl]benzene-1,3-diol | |
| CN105541816A (en) | Synthetic method of Ipragliflozin | |
| CN102167716A (en) | Synthesis method of clofarabine, midbody thereof and preparation method of midbody | |
| CN101318986B (en) | Method for synthesizing eplerenone | |
| CN107793302A (en) | A kind of method for preparing 10,10 disubstituted 2 bromine anthrones | |
| CN103086859A (en) | 2,4-dihydroxy-5,6-substituted-1-halogenobenzene derivative, synthesis method and application thereof | |
| CN108675972B (en) | Preparation method of amiodarone hydrochloride intermediate 2-butyl benzofuran | |
| CN106146457B (en) | 5-chloro-2-acyl chloride thiophene intermediate and preparation method thereof | |
| CN1281861A (en) | Preparation method of pentaerythritol phosphate | |
| CN107540655A (en) | A kind of new preparation S（Perfluoroalkyl）The method of dibenzothiophenes fluoroform sulphonate | |
| CN112125942B (en) | Synthetic method of abiraterone acetate and intermediate thereof | |
| CN108516944A (en) | A kind of preparation method of methane-disulfonic acid | |
| CN109053496A (en) | A kind of synthetic method of 3-Boc- aminomethyl cyclobutanone | |
| CN106432132A (en) | Preparation method of 2-arylbenzothiazole compound | |
| CN106588770A (en) | Use of cyclopropyl diphenylsulfonium trifluoromethanesulfonate as sulfur ylide reagent and method for preparation of four-membered cyclic ketone |
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 |