CN108341738A - It is used to prepare the method and its intermediate of eribulin - Google Patents
It is used to prepare the method and its intermediate of eribulin Download PDFInfo
- Publication number
- CN108341738A CN108341738A CN201810063859.5A CN201810063859A CN108341738A CN 108341738 A CN108341738 A CN 108341738A CN 201810063859 A CN201810063859 A CN 201810063859A CN 108341738 A CN108341738 A CN 108341738A
- Authority
- CN
- China
- Prior art keywords
- compound
- formula
- prepare
- salt
- analog
- 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
- 0 O=CCC*C1O*C2(CC2)C1 Chemical compound O=CCC*C1O*C2(CC2)C1 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C17/00—Preparation of halogenated hydrocarbons
- C07C17/013—Preparation of halogenated hydrocarbons by addition of halogens
- C07C17/04—Preparation of halogenated hydrocarbons by addition of halogens to unsaturated halogenated hydrocarbons
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C17/00—Preparation of halogenated hydrocarbons
- C07C17/093—Preparation of halogenated hydrocarbons by replacement by halogens
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C17/00—Preparation of halogenated hydrocarbons
- C07C17/093—Preparation of halogenated hydrocarbons by replacement by halogens
- C07C17/16—Preparation of halogenated hydrocarbons by replacement by halogens of hydroxyl groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C303/00—Preparation of esters or amides of sulfuric acids; Preparation of sulfonic acids or of their esters, halides, anhydrides or amides
- C07C303/26—Preparation of esters or amides of sulfuric acids; Preparation of sulfonic acids or of their esters, halides, anhydrides or amides of esters of sulfonic acids
- C07C303/28—Preparation of esters or amides of sulfuric acids; Preparation of sulfonic acids or of their esters, halides, anhydrides or amides of esters of sulfonic acids by reaction of hydroxy compounds with sulfonic acids or derivatives thereof
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C309/00—Sulfonic acids; Halides, esters, or anhydrides thereof
- C07C309/63—Esters of sulfonic acids
- C07C309/72—Esters of sulfonic acids having sulfur atoms of esterified sulfo groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton
- C07C309/73—Esters of sulfonic acids having sulfur atoms of esterified sulfo groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton to carbon atoms of non-condensed six-membered aromatic rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
- C07D307/26—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
- C07D307/28—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D493/00—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system
- C07D493/22—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system in which the condensed system contains four or more hetero rings
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The present invention provides the methods and its intermediate that are used to prepare eribulin.Specifically, the present invention provides a kind of preparation process of 3 methyl fourth of (3R) 2,4 dihalo-, 1 alkene (compound of formula I), wherein X is the halogens such as iodine, bromine or chlorine.Additionally provide the preparation method that compound of formula I is used to prepare halichondrins and its derivative, such as eribulin.
Description
Technical field
The present invention relates to the preparation methods of (3R) -2,4- dihalo- -3- methyl but-1-enes.
Background technology
Halichondrin B (Halichondrin B) is a kind of natural products with anti-tumor activity, initially from ocean sea
It is isolated in the continuous soft sponge of black.The first macrocyclic ketone analog that eribulin is obtained by halichondrin B structure optimization, at present
Methanesulfonic acid eribulin injection is in multiple country's listings, for treating metastatic breast cancer.
US6214865 and US5436238 is reported respectively with disubstituted (2S, the 5S) -3- methylene-tetrahydrochysenes of compound 2,5-
Furans (formula B-12 compounds) is the method that intermediate synthesizes halichondrins and its derivative,
Angew.Chem.Int.Ed.2009,48,2346 is reported with two iodo- 3- methyl but-1-ene (formulas 1 of (3R) -2,4-
Compound) it is the method that raw material obtains formula B-12 compounds,
CN104053645A, which is disclosed using compound 4-hydroxy base protecting group -3- methyl butyl- 1- alkynes as raw material, to be passed through addition, takes off
Protection, substitution prepare 2,4- dihalo- -3- methyl but-1-enes, but such method meeting by addition, deprotection, esterification, substitution
It generates the triphenylphosphine oxide by-product of more difficult removing and step is longer, while also being needed using expensive B-I-9-BBN in technique
Reagent is not suitable for industrial big production.Wherein PG is hydroxyl protection base,
Invention content
The present invention provides a kind of method being used to prepare compound of formula I,
This method includes：Converting Formula II compound to compound of formula I, wherein LG is leaving group or hydroxyl,
Wherein X is halogen, including Cl, Br, I.
It can be that one or multi-step reaction should if multistep reaction that the present invention is converted into compound of formula I by Formula II compound
Multistep reaction can be " one pot of multistep processes " or " one kettle way ".
In some embodiments, X can be identical or different in compound of formula I.
The leaving group of Formula II compound of the present invention is the molecule fragment that can be detached from scission of link step, leaving group
Group be not limited specifically and it is known to those skilled in the art dawn or can be determined.Formed leaving group embodiment include
But it is not limited to halogen or is based on sulfonic leaving group, halogen may include iodine, bromine or chlorine, preferably iodine；Based on sulfonic group
Leaving group can include but is not limited to perfluoro butyl methylsulphur acidic group, trifluoromethanesulfonic acid base, flurosulphonic acid base, toluenesulfonic acid
Base, methylsulphur acidic group or benzene sulfonic acid base, preferably toluenesulfonic acid base.
In embodiments, under the conditions of halide salt/halogenated silanes, the Formula II compound is converted into compound of formula I, institute
It is alkaline earth metal halide salt to state halide salt, can include but is not limited to LiI, NaI, KI, CsI, CaI2, MgI2, LiBr, NaBr,
KBr, CsBr, CaBr2, MgBr2, LiCl, NaCl, KCl, CsCl, CaCl2, MgCl2, preferably lithium iodide (LiI), sodium iodide
(NaI)；The halogenated silanes is known described in those skilled in the art or it is believed that is selected from but not limited to trimethyl iodine silicon
Alkane, triethiodide silane, bromotrimethylsilane, triethyl group bromo-silicane, trim,ethylchlorosilane, chlorotriethyl silane, preferably three
Methyl chloride SiClx.
In some embodiments, Formula II compound first with halogenation reactant salt formed -1 compound of Formula II, then with halide salt/
Halogenated silanes reacts to form compound of formula I, wherein X1It is halogen, including Cl, Br, I,
In some embodiments, Formula II compound first reacts to form -2 compound of Formula II with halide salt/halogenated silanes, then
Compound of formula I is formed with halogenation reactant salt, wherein X is halogen,
In some embodiments, with (S) -2- methyl butyl -3- alkynes -1- alcohol (1) be starting material, through hydroxyl be converted into from
After removing group, then reacted with halide salt/halogenated silanes and obtain compound 3：
In some embodiments, it can be gone through through reacting as follows for starting material with (S) -2- methyl butyl -3- alkynes -1- alcohol (1)
Journey obtains compound 3：
Further, wherein intermediate 1 or intermediate 2 can obtain through separation or directly carry out next step reaction without detaching
To obtain compound 3.
In some embodiments, halogen is converted to through hydroxyl for starting material with (S) -2- methyl butyl -3- alkynes -1- alcohol (1)
After element, then is reacted with halide salt/halogenated silanes and obtain compound of formula I：
Wherein X is iodine, bromine, chlorine.
It can contribute to obtain using the starting material of high enantiomeric purity and there is 3 compound of formula.In some implementations
In example, such as, but not limited to, the enantiomeric purity with any of 1 to 3 compound of formula is about 99.0%, 99.1%,
99.2%, 99.3%, 99.4%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%e.e. or between any value.
The present invention also provides Formula II compound, wherein LG is leaving group, it is preferable that the leaving group is based on sulfonic acid
The leaving group or halogen of base,
In embodiments, LG is toluenesulfonic acid base,
In some embodiments, LG is halogen, wherein X1For iodine, bromine, chlorine,
The method of formula B-12 compounds, including step described above, using step as follows, wherein instead
Answer condition such as Angew.Chem.Int.Ed.2009,48,2346；Org.Lett.2002,4,4435；
Described in J.Am.Chem.Soc.2009,131,15387 etc..
The method for being used to prepare halichondrins analog, including reaction step described above, using such as US6214865 or
Method described in US5436238 etc., the halichondrins analog can be eribulin or its officinal salt.
The method for being used to prepare halichondrins analog, including the use of above-mentioned Formula II compound synthesis halichondrins analog
The step of, the halichondrins analog can be eribulin or its officinal salt.
Eribulin of the present invention can be with acid at salt, and the acid is known to those skilled in the art or can determine
, selected from but not limited to hydrochloric acid, sulfuric acid, methanesulfonic acid, benzene sulfonic acid, toluenesulfonic acid, maleic acid, acetic acid, trifluoroacetic acid.
Specific implementation mode
The present invention is explained in greater detail below with reference to embodiment, the embodiment of the present invention is merely to illustrate the skill of the present invention
Art scheme, the spirit and scope of the invention are not limited thereto.
Embodiment 1：Prepare (2S) -2- methyl butyl- 3- alkynes -1- p-methyl benzenesulfonic acid esters
(2S) -2- methyl butyl- 3- alkynols (27.7g) are dissolved in the CH of 180mL dryings2Cl2In, then to system be added DMAP
(2.0g) and triethylamine (50.1g).It is cooled to -10 to -5 DEG C, the dichloromethane solution of TsCl (69.2g) is slowly added dropwise.It drips
At being warmed to room temperature naturally, continue stirring 2 hours, water (100mL) is added in the reaction was complete backward reaction solution.Separate organic layer, water
Layer uses CH again2Cl2Extraction merges organic layer.Organic phase washed with water, 1N aqueous hydrochloric acid solutions and saturated sodium bicarbonate aqueous solution are full
And brine It, it is dried with anhydrous sodium sulfate.Filtering after concentration, then through silica gel column separating purification obtains product 72.2g, yield：
92%.
Embodiment 2：Prepare two iodo- 3- methyl but-1-enes of (3R) -2,4-
LiI (88.8g) is weighed in reaction bulb, acetonitrile (500mL) is added, and TMSCl (42.6g), reaction solution is then added dropwise
It becomes cloudy, after five minutes, (2S) -2- methyl butyl- 3- alkynes -1- p-methyl benzenesulfonic acid esters (38.1g) are then added in stirring.At room temperature
After reaction 10 hours, water (200mL) is added, separates organic layer, water layer is extracted with MTBE again, merges organic layer.Organic phase is successively
With 10% sodium thiosulfate solution, saturated sodium bicarbonate aqueous solution and saturated common salt water washing, dried with anhydrous sodium sulfate.
Filtering after concentration, then through silica gel column separating purification obtains oily liquids product 44.8g, yield：87%.
Embodiment 3：Prepare the iodo- 3- methyl butyl- 1- alkynes of (3S) -4-
(2S) -2- methyl butyl- 3- alkynes -1- p-methyl benzenesulfonic acid esters (12.2g) are weighed in reaction bulb, and acetonitrile is added
(150mL), LiI (11.5g), after reacting 20h at room temperature, filtering, filter cake is washed with 50mL acetonitriles, after the concentration of gained filtrate
Oily liquids product 8.7g, yield：88%.
Embodiment 4：Prepare two iodo- 3- methyl but-1-enes of (3R) -2,4-
Weigh NaI (19.5g) in reaction bulb, acetonitrile (200mL) is added dropwise TMSCl (13.7g) at room temperature, reaction solution by
Gradual change is muddy, after stirring 30 minutes, the iodo- 3- methyl butyl- 1- alkynes (10.0g) of compound (3S) -4- is then added, at room temperature instead
After answering 12 hours, water (200mL) is added.Organic layer is separated, water layer is extracted with ether again, merges organic layer, successively with 10%
Sodium thiosulfate solution, saturated sodium bicarbonate aqueous solution and saturated common salt water washing, are dried with anhydrous sodium sulfate.Filtering, it is dense
Contracting, then obtain oily liquids product 15.1g, yield through silica gel column separating purification：91%.
Embodiment 5：Prepare the bromo- 3- methyl butyl- 1- alkynes of (3S) -4-
(2S) -2- methyl butyl- 3- alkynes -1- p-methyl benzenesulfonic acid esters (12.2g) are weighed in reaction bulb, and acetonitrile is added
(150mL), NaBr (15.8g), after reacting 20h at room temperature, filtering, filter cake is washed with 50mL acetonitriles, after the concentration of gained filtrate
Obtain oily liquids product 6.5g, yield：86%.
Embodiment 6：Prepare two iodo- 3- methyl but-1-enes of (3R) -2,4-
LiI (9.4g) is weighed in reaction bulb, acetonitrile (60mL) is added, TMSCl (4.3g) is then added dropwise, and reaction solution becomes muddy
Turbid, after five minutes, the bromo- 3- methyl butyl- 1- alkynes (2.3g) of (3S) -4- are then added in stirring.After reacting 10 hours at room temperature, add
Enter water (20mL), separate organic layer, water layer is extracted with MTBE again, merges organic layer.Organic phase successively with 10% thiosulfuric acid
Sodium water solution, saturated sodium bicarbonate aqueous solution and saturated common salt water washing, are dried with anhydrous sodium sulfate.Filtering, after concentration, then passes through
Silica gel column separating purification obtains oily liquids product 4.1g, yield：81%.
Embodiment 7：Prepare the iodo- 3- methyl butyl- 1- alkynes of (3S) -4-
The bromo- 3- methyl butyl- 1- alkynes (7.2g) of (3S) -4- are weighed in reaction bulb, and acetonitrile (150mL), LiI is added
(29.5g), after reacting 20h at room temperature, filtering, filter cake is washed with 50mL acetonitriles, and oily liquids production is obtained after the concentration of gained filtrate
Product 8.5g, yield：89%.
Embodiment 8：Prepare the iodo- 3- methyl butyl- 1- alkynes of (3S) -4-
By dichloromethane (25mL), triphenylphosphine (6.3g), imidazoles (1.8g), (2S) -2- methyl butyl- 3- alkynols (1.7g)
Solution be cooled to 5 DEG C, control temperature is slowly added I2 (6.1g) at 5-10 DEG C.Then room temperature reaction 1 hour is warmed naturally to
Afterwards, it is quenched with saturated sodium thiosulfate solution (100mL).Organic layer is separated, water layer uses dichloromethane (30mL) to extract again, merges
Organic layer.Organic layer is washed twice with water (50mL), is filtered after being dried over anhydrous sodium sulfate, concentration.Hexamethylene is added to residue
Alkane (100mL), filtering after concentration, then through silica gel column separating purification obtain oily liquids product 3.2g, yield：82%.
Claims (10)
1. the method for being used to prepare compound of formula I, wherein X are halogens；
This method includes：
Converting Formula II compound to compound of formula I, wherein LG is leaving group or hydroxyl,
It is preferred that the X is iodine.
2. the method according to claim 1 for being used to prepare compound of formula I, it is characterised in that the leaving group is to be based on
Sulfonic leaving group or halogen, it is described that perfluoro butyl sulfonic group, trifluoromethanesulfonic acid are selected from based on sulfonic leaving group
Base, flurosulphonic acid base, toluenesulfonic acid base, methylsulphur acidic group or benzene sulfonic acid base, preferably toluenesulfonic acid base.
3. method according to claim 1 or 2, it is characterised in that the Formula II compound and halide salt/halogenated silanes are anti-
Compound of formula I should be formed, the halide salt is alkaline earth metal halide salt, preferably lithium iodide, sodium iodide；The halogenated silanes choosing
From Iodotrimethylsilane, triethiodide silane, bromotrimethylsilane, triethyl group bromo-silicane, trim,ethylchlorosilane, triethylchloro-silicane
Alkane, preferably trimethylsilyl chloride.
4. according to the method described in claim 3, it is characterized in that Formula II compound forms -1 chemical combination of Formula II with halogenation reactant salt
Object, then react to form compound of formula I with halide salt/halogenated silanes, wherein X1It is halogen,
5. according to the method described in claim 3, it is characterized in that Formula II compound reacts the formula of being formed with halide salt/halogenated silanes
II-2 compounds, then compound of formula I is formed with halogenation reactant salt, wherein X is halogen,
6. Formula II compound, wherein LG are leaving groups, it is preferably based on sulfonic leaving group or halogen, more preferably first
Benzene sulfonic acid base or iodine,
7. a kind of method being used to prepare B-12 compounds, including such as Claims 1 to 5 any one of them method and pass through
The method that compound of formula I prepares B-12 compounds,
8. a kind of method being used to prepare B-12 compounds includes that the compound described in claim 6 prepares B-12 compounds
Step.
9. a kind of method being used to prepare halichondrins analog, including such as Claims 1 to 5 or 7~8 any one of them sides
Method and eribulin or the method for its officinal salt are prepared by compound of formula I, the halichondrins analog preferably ends
Bu Lin or its officinal salt.
10. a kind of method being used to prepare halichondrins analog, including the compound described in claim 6 prepare halichondrins
The step of the step of analog and the compound synthesis eribulin described in claim 6 or its officinal salt, the soft sea
Continuous element analog is preferably eribulin or its officinal salt.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710059583 | 2017-01-24 | ||
| CN2017100595839 | 2017-01-24 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN108341738A true CN108341738A (en) | 2018-07-31 |
| CN108341738B CN108341738B (en) | 2022-10-21 |
Family
ID=62960904
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201810063859.5A Active CN108341738B (en) | 2017-01-24 | 2018-01-23 | Process for the preparation of eribulin and intermediates thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN108341738B (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108689795A (en) * | 2017-04-11 | 2018-10-23 | 上海时莱生物技术有限公司 | A kind of intermediate and preparation method thereof being used to prepare eribulin |
| CN111875470A (en) * | 2020-08-17 | 2020-11-03 | 苏州正济药业有限公司 | Preparation method of intermediate (R) -2-methyl-1-bromo-3-iodo-3-butene for preparing eribulin |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1312804A (en) * | 1998-06-17 | 2001-09-12 | 卫材株式会社 | Macrocyclic analogs and methods of their use and preparation |
| CN104053645A (en) * | 2011-11-30 | 2014-09-17 | 阿方拉研究股份有限公司 | Process for preparation of (3R)-2,4-di-leaving group-3-methylbut-1-ene |
| WO2016176560A1 (en) * | 2015-04-30 | 2016-11-03 | President And Fellows Of Harvard College | Chromium-mediated coupling and application to the synthesis of halichondrins |
-
2018
- 2018-01-23 CN CN201810063859.5A patent/CN108341738B/en active Active
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1312804A (en) * | 1998-06-17 | 2001-09-12 | 卫材株式会社 | Macrocyclic analogs and methods of their use and preparation |
| CN104053645A (en) * | 2011-11-30 | 2014-09-17 | 阿方拉研究股份有限公司 | Process for preparation of (3R)-2,4-di-leaving group-3-methylbut-1-ene |
| WO2016176560A1 (en) * | 2015-04-30 | 2016-11-03 | President And Fellows Of Harvard College | Chromium-mediated coupling and application to the synthesis of halichondrins |
Non-Patent Citations (4)
| Title |
|---|
| DAE-SHIK KIM ET AL.: "New Syntheses of E7389 C14-C35 and Halichondrin C14-C38 Building Blocks: Double-Inversion Approach", 《JOURNAL OF THE AMERICAN CHEMICAL SOCIETY》 * |
| FANG LIU ET AL.: "On the regiochemistry of cyclialkylation of regiodefined 4-halo-1-alkenylmetals producing cyclobutenes", 《TETRAHEDRON LETTERS》 * |
| MARK I. KEMP ET AL.: "A Zirconium-Mediated Synthesis of (±)-Tecomanine", 《SYNTHESIS》 * |
| R. KARL DIETER ET AL.: "Copper mediated scalemic organolithium reagents in alkaloid syntheses", 《TETRAHEDRON》 * |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108689795A (en) * | 2017-04-11 | 2018-10-23 | 上海时莱生物技术有限公司 | A kind of intermediate and preparation method thereof being used to prepare eribulin |
| CN111875470A (en) * | 2020-08-17 | 2020-11-03 | 苏州正济药业有限公司 | Preparation method of intermediate (R) -2-methyl-1-bromo-3-iodo-3-butene for preparing eribulin |
| CN111875470B (en) * | 2020-08-17 | 2023-02-03 | 苏州正济药业有限公司 | Preparation method of intermediate (R) -2-methyl-1-bromo-3-iodo-3-butene for preparing eribulin |
Also Published As
| Publication number | Publication date |
|---|---|
| CN108341738B (en) | 2022-10-21 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| EP1423396A1 (en) | Synthesis of triphenylphosphonium quinols snd quinones | |
| CN104496979A (en) | Method for preparing oxazolidinone compound and intermediate thereof | |
| CN108341738A (en) | It is used to prepare the method and its intermediate of eribulin | |
| CN101790509A (en) | Process for preparing estrogen-antagonistic 11 ss-fluoro-17alpha-alkylestra-1,3,5(10)-triene-3,17-diols having a 7alpha-(xi-alkylamino-omega-perfluoroalkyl)alkyl side chain and a-alkyl(amino)-omega-perfluoro(alkyl)alkanes and processes for their preparation | |
| CN106749335B (en) | A kind of preparation method and application of halogenated oxygen cephalo-type intermediate | |
| KR102513651B1 (en) | Method for producing ether compound | |
| CN103922976B (en) | Asymmetry diaryl sulfone compounds and preparation method thereof | |
| JP4020141B2 (en) | Method for producing 1-acetoxy-3- (substituted phenyl) propene compound | |
| US8304580B2 (en) | Method for producing tris(perfluoroalkanesulfonyl)methide acid salt | |
| CN106905358B (en) | Preparation of vitamin D3Process for preparing analogue intermediates | |
| CN108707080B (en) | Environment-friendly synthesis method of linezolid and intermediate thereof | |
| CN113416142B (en) | Preparation method of 5-ALA intermediate 5-bromolevulinate | |
| CN109134250A (en) | A kind of synthetic method of β-iodo acetic acid esters compound | |
| JP4371402B2 (en) | Preparation of halogenated aryl-substituted cyclic tetrasiloxanes | |
| CN107011376A (en) | A kind of preparation method of sensitizing agent HF20 tpip for visible and infrared emission lanthanide series | |
| JP4075923B2 (en) | 1-acetoxy-3- (substituted phenyl) propene compound | |
| JP4093842B2 (en) | Method for producing halogenated adamantanes | |
| JP4495670B2 (en) | Method for producing mercaptoalkylphosphonium compounds | |
| KR100208427B1 (en) | A process for producing d, l, -3-methyl-cyclopentadecan-1-one | |
| JP2004010486A (en) | Method of producing fluorinated aryl group-containing compound | |
| CN109384763A (en) | The manufacturing method of 2- (2- halogenated ethyl) -1,3- dioxolanes | |
| CN116940545A (en) | Method for producing fluorine-containing compound, and fluorine-containing compound | |
| JP2000247988A (en) | Production of optically active vinylphosphine oxide | |
| SU707903A1 (en) | Method of purifying iodobenzenes | |
| CN115353437A (en) | Synthesis method of cis-2-methyl-7-octadecene and cis-7,8-epoxy-2-methyloctadecane |
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 |