CN106588868A - Synthesis method of 2-bromo-3-thiophenic acid intermediate - Google Patents
Synthesis method of 2-bromo-3-thiophenic acid intermediate Download PDFInfo
- Publication number
- CN106588868A CN106588868A CN201611030492.4A CN201611030492A CN106588868A CN 106588868 A CN106588868 A CN 106588868A CN 201611030492 A CN201611030492 A CN 201611030492A CN 106588868 A CN106588868 A CN 106588868A
- Authority
- CN
- China
- Prior art keywords
- bromo
- thiophene
- solvent
- synthetic method
- bromomethyl
- 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.)
- Pending
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
- C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
- C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
- C07D333/26—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D333/38—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
- C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
- C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
- C07D333/26—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D333/28—Halogen atoms
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention relates to a new synthesis method of 2-bromo-3-thiophenic acid, wherein the synthesis method comprises the following synthesis steps: 1) with 3-methyl thiophene as a raw material, adding N-bromosuccinimide to synthesize 2-bromo-3-methyl thiophene; 2) synthesizing 2-bromo-3-(bromomethyl)thiophene from 2-bromo-3-methyl thiophene and N-bromosuccinimide with carbon tetrachloride as a solvent and azodiisobutyronitrile as an initiator; 3) oxidizing 2-bromo-3-(bromomethyl)thiophene by 2-iodoxy benzoic acid to obtain 2-bromo-3-thiophenealdehyde; and 4) oxidizing 2-bromo-3- thiophenealdehyde by potassium permanganate to obtain 2-bromo-3-thiophenic acid with a sodium hydroxide solution as a solvent. The synthesis method has the beneficial effects that a synthetic route of firstly carrying out bromine substitution on a No.2 site and then oxidizing a No.3 site, the reaction conditions are mild, the reactants are cheap and easy to obtain, and the yield is relatively high; and secondly, di-bromide products are greatly inhibited, and the yield is improved.
Description
Technical field
The invention belongs to organic compound synthesis field, is related to a kind of chemical combination as organic semiconducting materials synthesis material
The new synthetic method of thing, is specifically synthesized the new synthetic method of the bromo- thenoic acids of 2- by 3 methyl thiophene.
Background technology
The sub- device of photoconductive organic semiconductor, including organic field effect tube, Organic Light Emitting Diode, organic photovoltaic electricity
Pond, organic electrostatic duplicating, organic laser and organic-biological sensor etc., because having, cheap, body is light to be taken, is easy to big face
The advantages of product processing and obtained extensive development and progressively strided forward to industrialization.Past 10 years, by the molecule to material
The optimization of structure design and device, organic semiconductor device has also obtained development at full speed, but in organic semiconducting materials
Still there are many obstacles in building-up process, the problems such as the synthesis of many intermediate has low-yield high cost, this is accomplished by optimization
Synthetic route is improved, more reasonably synthetic schemes is obtained.
Synthesize field in including but not limited to organic semiconducting materials, the bromo- thenoic acids of 2- are that one kind has extensive answering
Midbody compound, for all kinds of polymer or small molecule of thienyl-containing group in synthesizing main chain or side chain.Present
General synthetic method is to first pass through 3 methyl thiophene or the oxidation of 3- iodothiophens obtains thenoic acid, then by under low temperature and fourth
With expensive CBr after the reaction of base lithium4Act on No. 2 positions and realize that bromine replacement obtains the bromo- thenoic acids of 2-, this method reaction is needed
Ultra-low temperature surroundings and organic lithium salt strong base reagent, yield is wanted also than relatively low, to cause cost to greatly improve.Due to the bromo- 3- thiophene of 2-
Formic acid is widely used and demand is big, develops efficient variation route and has great practical value.
The content of the invention
The technical problem to be solved is to provide a kind of bromo- thenoic acids of synthesis 2- for above-mentioned prior art
New method, the route reaction condition is gentle, and agents useful for same is cheap and easy to get, and yield is higher.
The present invention for the technical scheme that adopted of solution above-mentioned technical problem for:A kind of bromo- thenoic acid intermediate of 2-
Synthetic method, including following synthesis step:
Step (1):By 3 methyl thiophene be raw material with chloroform and glacial acetic acid as solvent, add N- bromos succinyl sub-
Bromo- 3 methylthiophenes of amine synthesis 2-;
Step (2):By bromo- 3 methylthiophenes of 2- with carbon tetrachloride as solvent, azodiisobutyronitrile be initiator and N- bromos
Bromo- 3- (bromomethyl) thiophene of succimide synthesis 2-;
Step (3):By 2- bromo- 3- (bromomethyl) thiophene with dimethyl sulfoxide as solvent, aoxidized by 2- iodosobenzoic acids
Obtain the bromo- 3- thiophenecarboxaldehydes of 2-;
Step (4):By the bromo- 3- thiophenecarboxaldehydes of 2- with sodium hydrate aqueous solution as solvent, 2- is obtained by potassium permanganate oxidation
Bromo- thenoic acid.
By such scheme, in step (1), the ratio of the mole that feeds intake of 3 methyl thiophene and N- bromo-succinimides is 1:
1, the chloroform and glacial acetic acid volume ratio as solvent is 1:1;At 0 DEG C, the response time is 2-3h to described reaction temperature.
By such scheme, in step (1), control concentration of the 3 methyl thiophene in chloroform and glacial acetic acid for 0.5~
0.8mol/L。
By such scheme, in step (2), the ratio of the mole that feeds intake of bromo- 3 methylthiophenes of 2- and N- bromo-succinimides
For 1:1;Described reaction temperature must be controlled at 100 DEG C, and the response time is 60~70min, and reaction atmosphere is inert atmosphere.
By such scheme, in step (3), the mole that feeds intake of the bromo- 3- of 2- (bromomethyl) thiophene and 2- iodosobenzoic acids
Ratio be 1:1.6;Described reaction temperature is controlled at 60-70 DEG C, and the response time is 3-4h.
By such scheme, in step (4), the bromo- 3- thiophenecarboxaldehydes of 2- are 1 with the ratio of the mole that feeds intake of potassium permanganate:1;
At 50 DEG C, the response time is 2h to described reaction temperature.
Wherein, in step (1), more specifically operation is:In two neck flasks, addition 3 methyl thiophene, addition chloroform/
Glacial acetic acid (makes reactant concentration in about 0.6mol/L, be conducive to suppressing double bromination products), and NBS is dividedly in some parts in ice-water bath,
Continue to stir after NBS is added and finished;In step (1), after the reaction terminates, also it is quenched instead including post processing deionized water
Should, point liquid, organic faciess Jing NaOH solution, washing are dried, and water pump vacuum fractionation is used after concentration.
In step (2), more specifically operation is:Bromo- 3 methylthiophenes of 2- are added in two neck flasks, barrier film pumping is used
Vacuum makees Non-aqueous processing, in N2Protection is lower to add NBS and AIBN, adds CCl4, it is heated to reflux in oil bath;The reaction knot
Shu Hou, also cools down including post processing frozen water, filters, petroleum ether rinse, and membrane pump vacuum distillation is treated in concentration.
In step (3), more specifically operation is:Add bromo- 3- (bromomethyl) thiophene of 2- in two neck flasks, oil pump without
Water process.N2Protection is lower to add IBX, adds anhydrous DMSO, heats in oil bath;After the reaction terminates, also go including post processing
Ionized water is quenched reaction.Dichloromethane extraction point liquid, massive laundering dichloromethane phase has white solid to separate out, collected by suction filter
Liquid, is dried, and concentrates column chromatography while hot.
In step (4), more specifically operation is:Deionized water, NaOH (and the bromo- 3- thiophene of 2- are added in pear shape bottle
Formaldehyde, is dividedly in some parts KMnO4, stirred in water bath.Also include post processing sucking filtration while hot, extract filtrate, dense salt is added in Xiang Shuixiang
Acid, sucking filtration.
Main chemical reactions process involved in the present invention is as follows:
Compared with prior art, the invention has the beneficial effects as follows:
First, for the bromo- thenoic acid general lines of synthesis 2-, usually adopt and first No. 3 positions are aoxidized, obtain 3-
Thiophenic acid, then with expensive CBr4 act on No. 2 positions under -78 DEG C of low temperature and after butyl lithium reaction and realize that bromine replaces and obtain
The bromo- thenoic acids of 2-, yield is also than relatively low.The present invention has abandoned the traditional method that bromine replaces after initial oxidation, using first to No. 2
Position carries out bromine replacement, then to the synthetic route that No. 3 positions are aoxidized, can effectively suppress the disubstituted of bromine, reduces by-product
Produce, improve yield, reaction condition is gentle, and reactant is cheap and easy to get, and yield is higher.
Second, for the synthesis bromo- 3 methyl thiophenes of 2-, using chloroform/glacial acetic acid mixed liquor is as solvent and makes reactant
Concentration keeps reduced levels (about 0.6mol/L), can significantly suppress double bromination products, improves yield.
Specific embodiment
In order that the technical problem to be solved in the present invention, technical scheme and beneficial effect become more apparent, below in conjunction with
Example, the present invention will be described in further detail.It should be appreciated that specific embodiment described herein is only to explain this
Invention, is not intended to limit the present invention.
Embodiment 1
1st, the preparation of the bromo- 3 methyl thiophenes of compound 2-, reaction equation is as follows:
In the neck flasks of 1L bis-, 24.5g 3 methyl thiophenes (98g mol are added-1, 24.5g, 250mmol), add 400mL
Chloroform/glacial acetic acid (V:V=1:1, make reactant concentration about in 0.6mol/L, be conducive to suppressing double bromination products), in ice-water bath
In be dividedly in some parts 44.5g NBS (178g mol-1, 44.5g, 250mmol).Continue to stir 2-3 hours after NBS is added and finished,
TLC is monitored.
Post processing:Deionized water is quenched reaction, point liquid, organic faciess Jing NaOH solution, washing, is dried, and water pump is used after concentration
Vacuum fractionation.The sample that boiling range is 95 DEG C/50mmHg is collected,1H NMR:(500MHz,CDCl3)δ2.22(s,3H),7.17(d,J
=6.5Hz, 8H), 6.78 (d, J=6.5Hz, 4H), yield:83%.
2nd, the preparation of the bromo- 3- of compound 2- (bromomethyl) thiophene, reaction equation is as follows:
10g3- methylthiophenes (177g mol are added in the neck flasks of 250mL bis--1, 10g, 56mmol), it is true with barrier film pumping
Sky makees Non-aqueous processing, and under N2 protections 10g NBS (178g mol are added-1, 10g, 56mmol) and 15mg AIBN, add
100ml CCl4, 60-70 minutes, TLC monitorings are heated to reflux in 100 DEG C of oil baths.
Post processing:Frozen water is cooled down, and is filtered, petroleum ether, and concentration, water pump vacuum distillation collects 115 DEG C/50mm Hg's
Product.1H NMR:(500MHz,CDCl3) δ 4.45 (d, J=3Hz, 2H), 7.00 (d, J=7Hz, H), 7.25~7.27 (m, H),
Yield:75%.
3rd, the preparation of the bromo- 3- thiophenecarboxaldehydes of compound 2-, reaction equation is as follows:
Bromo- 3- (bromomethyl) thiophene (the 256g mol of 11.9g2- are added in the neck flasks of 250ml bis--1,11.9g,
46mmol), oil pump Non-aqueous processing.N2 protections are lower to add 20.8g IBX (280g mol-1, 20.8g, 74mmol, 1.6equiv),
The anhydrous DMSO of 130ml are added, 3-4 hours are heated in 60-70 DEG C of oil bath.
Post processing:Add 20ml deionized waters that reaction is quenched.Dichloromethane extraction point liquid, massive laundering dichloromethane phase,
There is white solid to separate out, collected by suction filtrate is dried, and concentrates column chromatography.Eluent petroleum ether/ethyl acetate 40:1(V:V).1H
NMR(500MHz,CDCl3) δ 7.27~7.30 (m, H), 7.36 (d, J=7.5Hz, H), 9.94 (s, H), yield:78.8%.
4th, the preparation of the bromo- thenoic acids of compound 2-, reaction equation is as follows:
8ml deionized waters, the bromo- 3- thiophenecarboxaldehydes of 0.6g NaOH (15mmol) and 1.9g 2- are added in 50ml pear shape bottles
(190g mol-1, 10mmol), 1.58g KMnO4(158g mol-1, 10mmol), 50 DEG C of stirred in water bath 2 hours.Take out while hot
Filter, extraction point liquid, water is added concentrated hydrochloric acid sucking filtration and obtains white solid,1H NMR(500MHz,CDCl3) δ 7.26~7.27 (m, H),
7.44 (d, J=7Hz, H), 11.25 (s, H), yield:70%.
Common four-step reaction, total recovery about 35%.
Synthetic route of the present invention replaces the thinking of rear oxidation using first bromine, and reaction condition is gentle, and reactant is inexpensively easy
, yield is higher.
Comparative example 2 (conventional method, concrete technology reference implementation example 1)
1st, the preparation of compound 3- (bromomethyl) thiophene, reaction equation is as follows:
Reaction temperature is 70 DEG C, response time 2h, yield about 75%.
2nd, the preparation of compound 3- thiophenecarboxaldehydes, reaction equation is as follows:
Reaction temperature is 80 DEG C, response time 4h, yield about 70%.
3rd, the preparation of compound thenoic acid, reaction equation is as follows:
Reaction temperature is zero degree, response time 3h, yield about 80%.
4th, the preparation of the bromo- thenoic acids of compound 2-, reaction equation is as follows:
Reaction temperature is -78 DEG C, response time 2h, yield about 50%.
Common four-step reaction, total recovery about 20%.
Conventional method using initial oxidation bromo again thinking, reaction condition is more harsh, and reactant price used is higher, and
And because in step 4 pairs of bromination product is more, cause yield relatively low.
Claims (6)
1. a kind of synthetic method of the bromo- thenoic acid intermediate of 2-, including following synthesis step:
Step (1):By 3 methyl thiophene be raw material with chloroform and glacial acetic acid as solvent, add N- bromo-succinimides to close
Into bromo- 3 methylthiophenes of 2-;
Step (2):By bromo- 3 methylthiophenes of 2- with carbon tetrachloride as solvent, azodiisobutyronitrile be initiator and N- bromos fourth two
Bromo- 3- (bromomethyl) thiophene of acid imide synthesis 2-;
Step (3):By 2- bromo- 3- (bromomethyl) thiophene with dimethyl sulfoxide as solvent, obtained by the oxidation of 2- iodosobenzoic acids
The bromo- 3- thiophenecarboxaldehydes of 2-;
Step (4):By the bromo- 3- thiophenecarboxaldehydes of 2- with sodium hydrate aqueous solution as solvent, the bromo- 3- of 2- are obtained by potassium permanganate oxidation
Thiophenic acid.
2. a kind of synthetic method of the bromo- thenoic acid intermediate of 2- according to claim 1, it is characterised in that step
(1) in, the ratio of the mole that feeds intake of 3 methyl thiophene and N- bromo-succinimides is 1:1, as solvent chloroform and
Glacial acetic acid volume ratio is 1:1;At 0 DEG C, the response time is 2-3h to described reaction temperature.
3. a kind of synthetic method of the bromo- thenoic acid intermediate of 2- according to claim 1, it is characterised in that step
(1) in, concentration of the 3 methyl thiophene in chloroform and glacial acetic acid is controlled for 0.5~0.8mol/L.
4. a kind of synthetic method of the bromo- thenoic acid intermediate of 2- according to claim 1, it is characterised in that step
(2) in, the ratio of the mole that feeds intake of bromo- 3 methylthiophenes of 2- and N- bromo-succinimides is 1:1;Described reaction temperature must
Must control at 100 DEG C, the response time is 60~70min, and reaction atmosphere is inert atmosphere.
5. a kind of synthetic method of the bromo- thenoic acid intermediate of 2- according to claim 1, it is characterised in that step
(3) in, the bromo- 3- of 2- (bromomethyl) thiophene is 1 with the ratio of the mole that feeds intake of 2- iodosobenzoic acids:1.6;Described reaction temperature
At 60-70 DEG C, the response time is 3-4h for degree control.
6. a kind of synthetic method of the bromo- thenoic acid intermediate of 2- according to claim 1, it is characterised in that step
(4) in, the bromo- 3- thiophenecarboxaldehydes of 2- are 1 with the ratio of the mole that feeds intake of potassium permanganate:1;Described reaction temperature at 50 DEG C, instead
It is 2h between seasonable.
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201611030492.4A CN106588868A (en) | 2016-11-16 | 2016-11-16 | Synthesis method of 2-bromo-3-thiophenic acid intermediate |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201611030492.4A CN106588868A (en) | 2016-11-16 | 2016-11-16 | Synthesis method of 2-bromo-3-thiophenic acid intermediate |
Publications (1)
Publication Number | Publication Date |
---|---|
CN106588868A true CN106588868A (en) | 2017-04-26 |
Family
ID=58592505
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN201611030492.4A Pending CN106588868A (en) | 2016-11-16 | 2016-11-16 | Synthesis method of 2-bromo-3-thiophenic acid intermediate |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN106588868A (en) |
Cited By (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN110878080A (en) * | 2019-12-09 | 2020-03-13 | 南京杰运医药科技有限公司 | Preparation method of 3-thiophenecarboxaldehyde |
CN113480517A (en) * | 2021-07-30 | 2021-10-08 | 海南海神同洲制药有限公司 | Synthetic method of 3-bromomethyl-7-chlorobenzo [ b ] thiophene |
CN114213358A (en) * | 2021-12-22 | 2022-03-22 | 上海泰坦科技股份有限公司 | Synthetic method of 2-bromo-5-formaldehyde thiazole |
Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1998042347A1 (en) * | 1997-03-25 | 1998-10-01 | Takeda Chemical Industries, Ltd. | Pharmaceutical composition containing a phosphorylamide and an ayntibiotic |
CN1575286A (en) * | 2001-10-25 | 2005-02-02 | 伊莱利利公司 | Thiophene-amd thiazolesulfonamides as antineoplastic agents |
CN1688588A (en) * | 2002-10-03 | 2005-10-26 | 阿斯利康(瑞典)有限公司 | Process and intermediates for the preparation of thienopyrrole derivatives |
-
2016
- 2016-11-16 CN CN201611030492.4A patent/CN106588868A/en active Pending
Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1998042347A1 (en) * | 1997-03-25 | 1998-10-01 | Takeda Chemical Industries, Ltd. | Pharmaceutical composition containing a phosphorylamide and an ayntibiotic |
CN1575286A (en) * | 2001-10-25 | 2005-02-02 | 伊莱利利公司 | Thiophene-amd thiazolesulfonamides as antineoplastic agents |
CN1688588A (en) * | 2002-10-03 | 2005-10-26 | 阿斯利康(瑞典)有限公司 | Process and intermediates for the preparation of thienopyrrole derivatives |
Non-Patent Citations (2)
Title |
---|
E. CAMPAIGNE,ET AL.,: "3-Substituted Thiophenes. III. Antihistaminics of the N-(S-Thenyl)- ethylenediamine Series", 《J. AM.CHEM.SOC.》 * |
JARUGU NARASIMHA MOORTHY,ET AL.,: "Steady-state photochemistry (Pschorr cyclization) and nanosecond transient absorption spectroscopy of twisted 2-bromoaryl ketones", 《PURE APPL. CHEM.》 * |
Cited By (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN110878080A (en) * | 2019-12-09 | 2020-03-13 | 南京杰运医药科技有限公司 | Preparation method of 3-thiophenecarboxaldehyde |
CN113480517A (en) * | 2021-07-30 | 2021-10-08 | 海南海神同洲制药有限公司 | Synthetic method of 3-bromomethyl-7-chlorobenzo [ b ] thiophene |
CN114213358A (en) * | 2021-12-22 | 2022-03-22 | 上海泰坦科技股份有限公司 | Synthetic method of 2-bromo-5-formaldehyde thiazole |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CN106588868A (en) | Synthesis method of 2-bromo-3-thiophenic acid intermediate | |
CN105348045B (en) | A kind of method of utilization continuous stream reaction synthesis Pentafluorophenol | |
CN103724261B (en) | A kind of industrialized process for preparing of hydroxychloroquine sulfate quinoline | |
CN108715574A (en) | A method of synthesis '-biphenyl diphenol | |
CN103896855B (en) | The synthetic method of the fluoro-6-chlorine of a kind of 4-(1-bromoethyl)-5-pyrimidine | |
CN106380450B (en) | A kind of preparation method of low energy consumption glyoxaline ion liquid | |
JP5837584B2 (en) | Method for producing chlorohydrin and method for producing epichlorohydrin using chlorohydrin produced by the method | |
CN107129556B (en) | Convertible smart fabric finishing agent of a kind of close and distant property in surface and preparation method thereof | |
CN107915689A (en) | The preparation method of the western Nader of thunder | |
WO2012002652A2 (en) | Method for preparing chlorohydrins composition and method for preparing epichlorohydrin using chlorohydrins composition prepared thereby | |
CN107473948A (en) | A kind of synthetic method that the pentanone of 3,5 dichloro 2 is prepared by ethyl acetoacetate | |
CN109053679B (en) | Preparation method of dessimutan oxidant | |
KR20120002336A (en) | Method of preparing composition of chlorohydrins and method of preparing epichlorohydrin using composition of chlorohydrins prepared by the same | |
CN104672168B (en) | A kind of preparation method of 2 methyl, 4 trifluoromethyl thiazole 5 formic acid | |
CN106892873A (en) | A kind of preparation method of 5 trifluoromethyl uracil | |
WO2012002651A2 (en) | Method for preparing chlorohydrins composition and method for preparing epichlorohydrin using chlorohydrins composition prepared thereby | |
CN103387584A (en) | Synthetic method of 7-amino-3-chloro-3-cephem-4-carboxylic acid | |
CN111377859B (en) | Preparation method of 7-chloro-8-methylquinoline | |
CN105481833B (en) | A kind of preparation method of Rupatadine fumarate | |
JP2003183268A (en) | Method for producing aromatic aldehyde | |
JP5837585B2 (en) | Method for producing chlorohydrin and method for producing epichlorohydrin using chlorohydrin produced by the method | |
CN106565625B (en) | A kind of antiplatelet reduces the preparation method of disease new drug Lusutrombopag intermediates | |
CN1185191C (en) | Process for preparation of alicyclic ketones and alkyl-substituted alicyclic esters | |
CN105367391A (en) | 2-chlorine-1,1,1-trimethoxyethane preparing method | |
CN110003006A (en) | A kind of preparation method of sour 7 side chains of latamoxef |
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 | ||
RJ01 | Rejection of invention patent application after publication | ||
RJ01 | Rejection of invention patent application after publication |
Application publication date: 20170426 |