CN104761592A - Method for synthesis of beta-D-fructofuranosyl-alpha-D-glucopyranosyl-6-ester - Google Patents
Method for synthesis of beta-D-fructofuranosyl-alpha-D-glucopyranosyl-6-ester Download PDFInfo
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Abstract
A method for synthesis of beta-D-fructofuranosyl-alpha-D-glucopyranosyl-6-ester comprises the following steps: 1) providing a first reaction mixture comprising beta-D-fructofuranosyl-alpha-D-glucopyranoside, a reaction intermedium, an orthoester, a catalyst, and beta-D-fructofuranosyl-alpha-D-glucopyranosyl alkyl 4,6-orthoester and alkyl alcohol which are generated from the above raw materials; 2) removing the generated alkyl alcohol from the first reaction mixture, to provide a second reaction mixture basically containing no alkyl alcohol; and 3) adding water to the second reaction mixture, hydrolyzing beta-D-fructofuranosyl-alpha-D-glucopyranosyl alkyl 4,6-orthoester, to generate beta-D-fructofuranosyl-alpha-D-glucopyranosyl-4-ester and beta-D-fructofuranosyl-alpha-D-glucopyranosyl-6-ester, and then carrying out transposition to obtain beta-D-fructofuranosyl-alpha-D-glucopyranosyl-6-ester.
Description
Technical field:
The invention belongs to organic chemistry formulation preparation method technical field, be specifically related to the method for the improvement of synthesizing a kind of sweeting agent intermediate beta-D-fructofuranose base-α-D-pyranoglucose-6-ester.
Background technology:
Beta-D-fructofuranose base-α-D-pyranoglucose-6-ester is the important intermediate of synthesis artificial sweetening agent 4,1', 6' ,-three chloro-4,1', 6' ,-three deoxidation gala type sucrose.Existing synthesis beta-D-fructofuranose base-α-D-pyranoglucose-6-ester industrialized method can mainly contain two kinds, i.e. organotin method and ortho acid ester process.Organotin method needs that use a large amount of costlinesses, that toxicity is very large organotin, and needs after completion of the reaction reclaim as far as possible completely and reuse organotin, otherwise cost will rise greatly.This just causes, and the process costs of organotin method is high, complex operation is difficult, toxicity is large.Ortho acid ester process is simple to operate, is highly susceptible to industrialization, but it is lower to there is yield, causes the shortcoming that production cost is higher.
Summary of the invention
The present invention improves ortho acid ester process, the yield of beta-D-fructofuranose base-α-D-pyranoglucose-6-ester has been had and significantly improves, reduce production cost.Technical scheme of the present invention is as follows:
Synthesize a method for beta-D-fructofuranose base-α-D-pyranoglucose-6-ester, comprise the steps:
1) supply raw materials: raw material comprises: beta-D-fructofuranose base-α-D-pyranoglucose, reaction media thing, ortho ester and catalyzer; Described reaction media thing is polar aprotic solvent;
Raw material obtains beta-D-fructofuranose base-α-D-pyranoglucose alkyl 4,6-ortho ester and alkyl alcohol through cyclization;
In this step, polar aprotic solvent can be DMF (DMF), also can be the polar aprotic solvent of other realization response; Ortho ester is preferably trimethyl orthoacetate or triethly orthoacetate;
2) from the product of step 1), remove alkyl alcohol, obtain beta-D-fructofuranose base-α-D-pyranoglucose alkyl 4,6-ortho ester;
3) first to described step 2) product in add distilled water, make beta-D-fructofuranose base-α-D-pyranoglucose alkyl 4,6-ortho ester is hydrolyzed, and obtains beta-D-fructofuranose base-α-D-pyranoglucose-4-ester and beta-D-fructofuranose base-α-D-pyranoglucose-6-ester;
Again the acyl group of beta-D-fructofuranose base-α-D-pyranoglucose-4-ester is inserted to 6 (acyl group transpositions) from 4 and finally obtains beta-D-fructofuranose base-α-D-pyranoglucose-6-ester.The acyl group transposition of this step can adopt the 4-ester transposition under alkaline condition of the prior art to be the methods such as 6-ester.
In step 1), reaction method comprises the following two kinds:
Method 1: first beta-D-fructofuranose base-α-D-pyranoglucose and reaction media thing are mixed the mode that merga pass heats and make it dissolve, be then cooled to normal temperature, then add other material, react at normal temperatures 2 ~ 4 hours (preferably 3 hours); Wherein, Heating temperature is 80 ~ 90 DEG C;
Method 2: first all raw materials are first mixed at normal temperatures, then react at normal temperatures or react under heating condition, temperature of reaction is normal temperature ~ 100 DEG C (preferably normal temperature ~ 80 DEG C), and the reaction times is 1 ~ 20 hour (preferably 2 ~ 6 hours).
Beta-D-fructofuranose base-α-D-pyranoglucose in step 1) and the ratio of DMF (DMF) they are 1:1 ~ 1:8(w/w) (preferably 1:2 ~ 1:4(w/w)).
Described step 2) method comprise the following two kinds:
Method 1: by normal pressure or underpressure distillation, distillates the alkyl alcohol of generation and reaction media thing;
Method 2: lower by adding boiling point compared with reaction media thing, and the solvent do not reacted with any material in reaction mixture, then carry out normal pressure or underpressure distillation, thus take alkyl alcohol and reaction media thing at a lower temperature out of.
Step 2) method 1 identical with the distillation temperature of 2, be all 20 DEG C ~ 100 DEG C (preferably normal temperature ~ 80 DEG C), pressure during distillation can distill out alkyl alcohol and reaction media thing under meeting corresponding vacuum tightness and temperature.
Step 2) method 2 in, solvent used comprises: chloroform, methylene dichloride, tetracol phenixin, ethylene dichloride, 1,1,1-trichloroethane, 1, a kind of or several mixture in 1,2-trichloroethane, methyl acetate, ethyl acetate, butylacetate, benzene, toluene, hexane, hexanaphthene or sherwood oil.
The reaction conditions such as the feeding quantity in the technical program, catalyzer, hydrolysis, transposition, be described in disclosed document and patent, such as US4889928, US5449772, US5440026, these are easy to grasp to those skilled in the art, just limit no longer further here.
Advantage of the present invention is, compared with the prior art, owing to generating the second reaction mixture, the alkyl alcohol generated when namely having sloughed cyclization, makes cyclization be tending towards complete, and W-response yield is improved greatly.This does not have in existing processing method.And the beta-D-fructofuranose base-α-D-pyranoglucose-6-ester prepared by present method, only containing a small amount of unreacted beta-D-fructofuranose base-α-D-pyranoglucose, this is more prone to regard to making it to become the process of subsequent reactions thing, thus improve product yield on the whole, reduce cost.
Embodiment
The technique of present method comprises the following steps (normal temperature mentioned in the present invention refers to 20 DEG C):
1) supply raw materials, comprising: beta-D-fructofuranose base-α-D-pyranoglucose, reaction media thing, ortho ester and catalyzer; Be obtained by reacting and be obtained by reacting beta-D-fructofuranose base-α-D-pyranoglucose alkyl 4,6-ortho ester and alkyl alcohol by said mixture;
2) from step 1) product, generated methyl alcohol (in actual production, alkyl alcohol is methyl alcohol mainly) is removed, to provide substantially not containing beta-D-fructofuranose base-α-D-pyranoglucose alkyl 4, the 6-ortho ester of methyl alcohol;
3) to described step 2) add water in the product that obtains, make beta-D-fructofuranose base-α-D-pyranoglucose alkyl 4,6-ortho ester is hydrolyzed, and generates beta-D-fructofuranose base-α-D-pyranoglucose-4-ester and beta-D-fructofuranose base-α-D-pyranoglucose-6-ester; Beta-D-fructofuranose base-α-D-pyranoglucose-4-ester finally obtains beta-D-fructofuranose base-α-D-pyranoglucose-6-ester again through transposition.
Described reaction media thing is polar aprotic solvent, and it is preferably DMF (DMF).Ortho ester is preferably trimethyl orthoacetate or triethly orthoacetate.
In step 1),
Method 1: first beta-D-fructofuranose base-α-D-pyranoglucose and reaction media thing can be mixed the mode that merga pass heats and make it dissolve, then be cooled to normal temperature, then add other material;
Method 2: also all materials first can be mixed at normal temperatures, then react at normal temperatures or react under heating condition.
Beta-D-fructofuranose base-α-D-pyranoglucose in step 1) and the ratio of DMF are 1:1 ~ 1:8(w/w), preferred ratio is 1:2 ~ 1:4(w/w).Temperature of reaction, from 0 DEG C to 100 DEG C, is more preferably normal temperature to 80 DEG C.Reaction times is 1 ~ 20 hour, and more excellent is 2 ~ 6 hours.
Described step 2) thinking be that method 1: by normal pressure or underpressure distillation, distillates the alkyl alcohol of generation and reaction media thing;
Method 2: lower by adding certain boiling point compared with reaction media thing, and the solvent that can not react with any material in reaction mixture, then carry out normal pressure or underpressure distillation, thus take alkyl alcohol and reaction media thing at a lower temperature out of.
Described step 2) the temperature of distillation be normal temperature ~ 100 DEG C, preferred normal temperature ~ 80 DEG C.
Step 2) if employing method 2, solvent then used includes but not limited to: chloroform, methylene dichloride, tetracol phenixin, ethylene dichloride, 1,1,1-trichloroethane, 1,1, one in 2-trichloroethane, methyl acetate, ethyl acetate, butylacetate, benzene, toluene, hexane, hexanaphthene or sherwood oil, or several mixtures.
Below by specific embodiment, the present invention is described further.
Embodiment 1:
A 500ml tetra-mouthfuls of round-bottomed flasks, are equipped with mechanical stirring, thermometer and vacuum distillation apparatus.Wherein add 50g(0.146mol) beta-D-fructofuranose base-α-D-pyranoglucose, the DMF(relative density of 200ml is 0.9445).Being heated to 90 DEG C makes beta-D-fructofuranose base-α-D-pyranoglucose dissolve.Be cooled to 20 DEG C, add 21.5g(0.175mol) trimethyl orthoacetate, 0.3g tosic acid as catalyzer, stirring at room temperature 3 hours.
Underpressure distillation, keeps mixeding liquid temperature not higher than 60 DEG C, when steaming about 20ml liquid, stopping distillation, and mixeding liquid temperature is down to 20 DEG C.Add distilled water 20ml, stir 1 hour.In mixed solution, add 5ml TERTIARY BUTYL AMINE again, stir 2 hours.Water in underpressure distillation removing reaction system and TERTIARY BUTYL AMINE.
Sampling detects, wherein beta-D-fructofuranose base-α-D-pyranoglucose-6-acetate content 87.5% after eliminating solvent.Beta-D-fructofuranose base-α-D-pyranoglucose 6.5%.
Embodiment 2:
A 500ml tetra-mouthfuls of round-bottomed flasks, are equipped with mechanical stirring, thermometer and vacuum distillation apparatus.Wherein add 50g(0.146mol) beta-D-fructofuranose base-α-D-pyranoglucose, 200ml DMF, 21.5g(0.175mol) trimethyl orthoacetate, 0.3g tosic acid is as catalyzer.50 DEG C are heated to, insulation reaction 5h under stirring.
Underpressure distillation, keeps mixeding liquid temperature not higher than 60 DEG C, when steaming about 20ml liquid, stopping distillation, and mixeding liquid temperature is down to 20 DEG C.Add distilled water 20ml, stir 1 hour.
In mixed solution, add 5ml TERTIARY BUTYL AMINE again, stir 2 hours.Water in underpressure distillation removing reaction system and TERTIARY BUTYL AMINE.
Sampling detects, wherein beta-D-fructofuranose base-α-D-pyranoglucose-6-acetate content 84.5% after eliminating solvent.Beta-D-fructofuranose base-α-D-pyranoglucose 8.2%.
Embodiment 3:
A 500ml tetra-mouthfuls of round-bottomed flasks, are equipped with mechanical stirring, thermometer and vacuum distillation apparatus.Wherein add 50g(0.146mol) beta-D-fructofuranose base-α-D-pyranoglucose, 200ml DMF.Being heated to 90 DEG C makes beta-D-fructofuranose base-α-D-pyranoglucose dissolve.Be cooled to 20 DEG C, add 21.5g(0.175mol) trimethyl orthoacetate, 0.3g tosic acid as catalyzer, stirring at room temperature 3 hours.
Add 20ml ethylene dichloride, underpressure distillation.Keep mixeding liquid temperature not higher than 40 DEG C, when steaming about 40ml liquid, stopping distillation, and mixeding liquid temperature is down to 20 DEG C.Add distilled water 20ml, stir 1 hour.
In mixed solution, add 5ml TERTIARY BUTYL AMINE again, stir 2 hours.Water in underpressure distillation removing reaction system and TERTIARY BUTYL AMINE.
Sampling detects, wherein beta-D-fructofuranose base-α-D-pyranoglucose-6-acetate content 89.2% after eliminating solvent.Beta-D-fructofuranose base-α-D-pyranoglucose 6.3%.
Reference examples:
A 500ml tetra-mouthfuls of round-bottomed flasks, are equipped with mechanical stirring, thermometer and vacuum distillation apparatus.Wherein add 50g(0.146mol) beta-D-fructofuranose base-α-D-pyranoglucose, 200ml DMF.Being heated to 90 DEG C makes beta-D-fructofuranose base-α-D-pyranoglucose dissolve.Be cooled to 20 DEG C, add 21.5g(0.175mol) trimethyl orthoacetate, 0.3g tosic acid, stirring at room temperature 3 hours.Add distilled water 20ml, stir 1 hour.In mixed solution, add 5ml TERTIARY BUTYL AMINE again, stir 2 hours.Water in underpressure distillation removing reaction system and TERTIARY BUTYL AMINE.Sampling detects, wherein beta-D-fructofuranose base-α-D-pyranoglucose-6-acetate content 74.6% after eliminating solvent.Beta-D-fructofuranose base-α-D-pyranoglucose 16.3%.
Claims (10)
1. synthesize a method for beta-D-fructofuranose base-α-D-pyranoglucose-6-ester, it is characterized in that comprising the steps:
1) supply raw materials: raw material comprises: beta-D-fructofuranose base-α-D-pyranoglucose, reaction media thing, ortho ester and catalyzer; Described reaction media thing is polar aprotic solvent;
Raw material obtains beta-D-fructofuranose base-α-D-pyranoglucose alkyl 4,6-ortho ester and alkyl alcohol through cyclization;
2) from the product of step 1), remove alkyl alcohol, obtain beta-D-fructofuranose base-α-D-pyranoglucose alkyl 4,6-ortho ester;
3) first to described step 2) product in add distilled water, make beta-D-fructofuranose base-α-D-pyranoglucose alkyl 4,6-ortho ester is hydrolyzed, and obtains beta-D-fructofuranose base-α-D-pyranoglucose-4-ester and beta-D-fructofuranose base-α-D-pyranoglucose-6-ester;
Again the acyl group of beta-D-fructofuranose base-α-D-pyranoglucose-4-ester is inserted to 6 (refer to acyl group transposition or cry migration) from 4 and finally obtains beta-D-fructofuranose base-α-D-pyranoglucose-6-ester.
2. the method for synthesis beta-D-fructofuranose base-α-D-pyranoglucose-6-ester according to claim 1, it is characterized in that in the raw material of step 1), polar aprotic solvent is DMF (DMF); Ortho ester is trimethyl orthoacetate or triethly orthoacetate.
3. the method for synthesis beta-D-fructofuranose base-α-D-pyranoglucose-6-ester according to claim 1, is characterized in that, in step 1), reaction method comprises the following two kinds:
Method 1: first beta-D-fructofuranose base-α-D-pyranoglucose and reaction media thing are mixed the mode that merga pass heats and make it dissolve, be then cooled to normal temperature, then add other material, react 2 ~ 4 hours at normal temperatures;
Method 2: first all raw materials are first mixed at normal temperatures, then react at normal temperatures or react under heating condition, temperature of reaction is normal temperature ~ 100 DEG C, and the reaction times is 1 ~ 20 hour.
4. the method for synthesis beta-D-fructofuranose base-α-D-pyranoglucose-6-ester according to claim 1, is characterized in that, in step 1), reaction method comprises the following two kinds:
Method 1: first beta-D-fructofuranose base-α-D-pyranoglucose and reaction media thing are mixed the mode that merga pass heats and make it dissolve, be then cooled to normal temperature, then add other material, react 3 hours at normal temperatures; Wherein, Heating temperature is 80 ~ 90 DEG C;
Method 2: first all raw materials are first mixed at normal temperatures, then react at normal temperatures or react under heating condition, temperature of reaction is normal temperature ~ 80 DEG C, and the reaction times is 2 ~ 6 hours.
5. the method for the synthesis beta-D-fructofuranose base-α-D-pyranoglucose-6-ester according to Claims 2 or 3 or 4, the ratio that it is characterized in that beta-D-fructofuranose base-α-D-pyranoglucose in step 1) and DMF (DMF) is 1:1 ~ 1:8(w/w).
6. the method for the synthesis beta-D-fructofuranose base-α-D-pyranoglucose-6-ester according to Claims 2 or 3 or 4, the ratio that it is characterized in that beta-D-fructofuranose base-α-D-pyranoglucose in step 1) and DMF (DMF) is 1:2 ~ 1:4(w/w).
7. the method for synthesis beta-D-fructofuranose base-α-D-pyranoglucose-6-ester according to claim 1, step 2 described in it) method comprise the following two kinds:
Method 1: by normal pressure or underpressure distillation, distillates the alkyl alcohol of generation and reaction media thing;
Method 2: lower by adding boiling point compared with reaction media thing, and the solvent do not reacted with any material in reaction mixture, then carry out normal pressure or underpressure distillation, thus take alkyl alcohol and reaction media thing at a lower temperature out of.
8. the method for synthesis beta-D-fructofuranose base-α-D-pyranoglucose-6-ester according to claim 7, it is characterized in that step 2) method 1 identical with the distillation temperature of 2, be all normal temperature ~ 100 DEG C, pressure during distillation can distill out alkyl alcohol and reaction media thing under meeting corresponding vacuum tightness and temperature.
9. the method for synthesis beta-D-fructofuranose base-α-D-pyranoglucose-6-ester according to claim 7, it is characterized in that described step 2) method 1 identical with the distillation temperature in 2, be all normal temperature ~ 80 DEG C, pressure during distillation can distill out alkyl alcohol and reaction media thing under meeting corresponding vacuum tightness and temperature.
10. the method for the synthesis beta-D-fructofuranose base-α-D-pyranoglucose-6-ester according to claim 7 or 8 or 9, it is characterized in that step 2) method 2 in, solvent used comprises: chloroform, methylene dichloride, tetracol phenixin, ethylene dichloride, 1,1,1-trichloroethane, 1, a kind of or several mixture in 1,2-trichloroethane, methyl acetate, ethyl acetate, butylacetate, benzene, toluene, hexane, hexanaphthene or sherwood oil.
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Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4889928A (en) * | 1986-09-17 | 1989-12-26 | Tate & Lyle Public Limited Company | Sucrose alkyl 4,6-orthoacylates |
| CN101041676A (en) * | 2007-04-18 | 2007-09-26 | 江苏强盛化工有限公司 | Preparation method of saccharose-6-acetic acid esters |
| CN101367848A (en) * | 2007-08-15 | 2009-02-18 | 常州市牛塘化工厂有限公司 | Preparation method for sucrose-6- ethyl ester |
| CN103087116A (en) * | 2011-11-07 | 2013-05-08 | 常茂生物化学工程股份有限公司 | Sucralose preparation method |
-
2014
- 2014-01-07 CN CN201410006287.9A patent/CN104761592A/en active Pending
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4889928A (en) * | 1986-09-17 | 1989-12-26 | Tate & Lyle Public Limited Company | Sucrose alkyl 4,6-orthoacylates |
| CN101041676A (en) * | 2007-04-18 | 2007-09-26 | 江苏强盛化工有限公司 | Preparation method of saccharose-6-acetic acid esters |
| CN101367848A (en) * | 2007-08-15 | 2009-02-18 | 常州市牛塘化工厂有限公司 | Preparation method for sucrose-6- ethyl ester |
| CN103087116A (en) * | 2011-11-07 | 2013-05-08 | 常茂生物化学工程股份有限公司 | Sucralose preparation method |
Non-Patent Citations (1)
| Title |
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| 冷一欣等: "甜味剂三氯蔗糖的合成及结构表征", 《化学研究与应用》 * |
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