CN106748770A - A kind of simple and convenient process for preparing of felbinac - Google Patents
A kind of simple and convenient process for preparing of felbinac Download PDFInfo
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- CN106748770A CN106748770A CN201611196791.5A CN201611196791A CN106748770A CN 106748770 A CN106748770 A CN 106748770A CN 201611196791 A CN201611196791 A CN 201611196791A CN 106748770 A CN106748770 A CN 106748770A
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- felbinac
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C67/00—Preparation of carboxylic acid esters
- C07C67/30—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group
- C07C67/333—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group by isomerisation; by change of size of the carbon skeleton
- C07C67/343—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group by isomerisation; by change of size of the carbon skeleton by increase in the number of carbon atoms
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C51/00—Preparation of carboxylic acids or their salts, halides or anhydrides
- C07C51/02—Preparation of carboxylic acids or their salts, halides or anhydrides from salts of carboxylic acids
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C51/00—Preparation of carboxylic acids or their salts, halides or anhydrides
- C07C51/09—Preparation of carboxylic acids or their salts, halides or anhydrides from carboxylic acid esters or lactones
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Abstract
The invention provides a kind of simple and convenient process for preparing of felbinac.There is Friedel-Crafts reaction in the method, 4-acetylbiphenyl acetoacetic ester is generated under cryogenic with biphenyl and ethyl oxalyl chloride as initial feed under alchlor effect, then basic hydrolysis is 4-acetylbiphenyl hydrochlorate, and felbinac is obtained through huang-Minlon reaction reduction, acidifying.The method intermediate is not required to separate, and easy to operate, environment-friendly, total recovery is high, with industrial production value.
Description
Technical field
The present invention relates to a kind of simple and convenient process for preparing of felbinac, belong to medicinal chemistry art.
Background technology
Felbinac is the medicine that Japanese Lederle was listed in 1986 with the exploitation of " Napageln " ointment, and molecular formula is
C14H12O2, it is a kind of NSAIDs, is effective metabolite of brufen, and its anti-inflammatory activity is similar to brufen.At present,
Domestic preparation has been produced, and principal indication is：Modification arthritis, scapulohumeral periarthritis, tenosynovitis, peritendinitis, courbature, wound swells
It is swollen, pain etc..
The report of the existing various synthetic methods of document, so far, the process route for synthesizing felbinac mainly has following
It is several：
(1) patent CN 104086394A are disclosed to be the conjunction that raw material is initiation material preparation to bromo-acid, phenyl boric acid
Into route：
In above-mentioned synthetic method, reactions steps are shorter, and total recovery is higher；But raw material production cost is higher, and preparing
During need column chromatography, it is cumbersome, be not easy to industrialized production.
(2) Chinese patent document CN102993001A palladium chtalysts carbonylation prepares felbinac there is provided a kind of felbinac
Synthetic method, the method is：With 4- chloromethyl biphenyls as raw material, in catalyst palladium chloride, ligand triphenylphosphine, alkali, molten
In the presence of agent, and through there is carbonylation, then acidified, isolated felbinac in carbon monoxide.The method is due to using
Triphenylphosphine, during heat resolve, can generate poisonous hydrogen phosphide and POx smog, and operation is carried out in fume hood, used as reaction
Reagent, is subject to certain restrictions its industrial applications.
It is, thus, sought for a kind of more efficient, environment-friendly, with industrial production value method synthesizes biphenyl
Acetic acid, the present invention is proposed for this.
The content of the invention
In view of the shortcomings of the prior art, the present invention provides a kind of simple and convenient process for preparing of felbinac.The centre of the method
Body is not required to separate, and easy to operate, environment-friendly, total recovery is high, with industrial production value.
Technical scheme is as follows：
A kind of simple and convenient process for preparing of felbinac, comprises the following steps：
(1) with biphenyl and ethyl oxalyl chloride as initial feed, there is Friedel-Crafts reaction under alchlor effect, in low temperature
Under the conditions of generate 4-acetylbiphenyl acetoacetic ester；
(2) alkaline hydrolysis is 4-acetylbiphenyl hydrochlorate, is acted on hydrazine in the basic conditions, through huang-Minlon reaction reduction, acidifying
Obtain target compound felbinac；
According to currently preferred, the low temperature described in step (1) is -5~5 DEG C, more preferably -5~0 DEG C.
According to currently preferred, the reaction time is in 6~10h, more preferably 6h in step (1).
According to currently preferred, biphenyl used, ethyl oxalyl chloride and alchlor mol ratio are 1 in step (1):1
~2:2, more preferably 1:1.2:2.
According to currently preferred, the alkali described in step (2) is NaOH.
Of the invention more detailed, a kind of simple and convenient process for preparing of felbinac comprises the following steps：
(1) in four-hole boiling flask, nitrogen protection adds dichloroethanes 180ml, biphenyl 27.8g and aluminum trichloride (anhydrous)
36g, quick stirring is cooled to -5 DEG C, and in ethyl oxalyl chloride 29.5g is added dropwise in 1 hour, it is -5~5 that temperature is controlled during dropwise addition
℃；Drop finishes, and 6h~10h is reacted in 0 DEG C, and reaction is finished pours into 500mL concentrated hydrochloric acid ice water solutions reaction solution, and concentrated hydrochloric acid/
Frozen water volume ratio is 1~2：1；Stirring, point liquid, organic layer use saturated sodium-chloride water solution respectively, and saturated sodium bicarbonate water is molten
Liquid and purifying water washing to neutrality finish, anhydrous sodium sulfate drying；Filtering, is evaporated off organic solvent, obtains compound 4-acetylbiphenyl acid second
Ester；
(2) to 1mol/L NaOH solution 80mL are added in the compound obtained by step (1), 2-3 is stirred at room temperature small
When, there are a large amount of white sodium salts to separate out, 80mL water dissolves are added, after solid is completely dissolved, 4-acetylbiphenyl acid salt aqueous solution is obtained, treat
With；In 4-acetylbiphenyl acid salt aqueous solution, hydrazine hydrate 18.8g and the 15g sodium hydrate solid of mass concentration 75~85% is added, plus
Heat is incubated 3-4h, then heat temperature raising to 80 DEG C~85 DEG C, 100 DEG C is raised in 2h, and be incubated 6-8h in 100 DEG C；Cooling reaction
Liquid starts to less than 25 DEG C, and hydrochloric acid is added dropwise, and adjusts pH value, terminal is added dropwise and is counted with pH value as 3, and a large amount of white solids are separated out, mistake
Filter, filter cake purifying water washing, is washed till filter liquor in neutrality, obtains felbinac crude product；Crude product isopropanol is refining to obtain biphenyl second
Sour fine work.
According to currently preferred, the concentrated hydrochloric acid/frozen water volume ratio described in step (1) is 1:1.
According to currently preferred, it is -5 DEG C~0 to control temperature during dropwise addition ethyl oxalyl chloride described in step (1)
℃。
According to currently preferred, the mass concentration concentration of the hydrazine hydrate described in step (2) is 80%.
The present invention is not specified according to existing conventional techniques in method made above.
There is Friedel-Crafts reaction under alchlor effect with biphenyl and ethyl oxalyl chloride as initial feed in the present invention,
4-acetylbiphenyl acetoacetic ester is generated under cryogenic conditions, then basic hydrolysis is 4-acetylbiphenyl hydrochlorate, through huang-Minlon reaction reduction, is acidified and must join
Phenylacetic acid.Synthetic route of the present invention is as follows：
The invention provides a kind of brand-new preparation method of felbinac.The method raw material is easy to get, in the middle of compound reaction
Body is not required to separate, but directly carries out next step reaction with the mixed solution of water or other solvents, the step of separation with intermediate
Compare, high income of the present invention reaches 76%；Operation cycle is short, in a word, easy to operate, environment-friendly, total recovery of the invention is high,
With industrial production value.
Specific embodiment
With reference to specific embodiment, the present invention will be further described.
Embodiment 1：
A kind of simple and convenient process for preparing of felbinac, comprises the following steps：
(1) preparation of 4-acetylbiphenyl hydrochlorate
In 500mL four-hole boiling flasks, nitrogen protection adds dichloroethanes 180ml biphenyl 27.8g (0.18mol) and anhydrous
Alchlor 36g (0.27mol), quick stirring is cooled to -5 DEG C, in dropwise addition ethyl oxalyl chloride 29.5g in 1 hour
(0.25mol), controls -5 DEG C of temperature~5 DEG C during dropwise addition.Drop finishes, and 6h is reacted in 0 DEG C, and reaction is finished pours into dense salt by reaction solution
In acid/frozen water 500mL, V (concentrated hydrochloric acid)/V (frozen water)=1：1；Stirring, point liquid, organic layer are water-soluble with saturated sodium-chloride respectively
Liquid, saturated sodium bicarbonate aqueous solution and purification of aqueous solutions are washed to neutrality to be finished, anhydrous sodium sulfate drying；Filtering, is evaporated off organic molten
Agent, obtains compound 4-acetylbiphenyl acetoacetic ester；
(2) synthesis of felbinac
To 1mol/L NaOH solution 80mL are added in the compound obtained by step (1), it is stirred at room temperature 2 hours, there is big
The white sodium salt of amount is separated out, and adds 80mL water dissolves, after solid is completely dissolved, obtains 4-acetylbiphenyl acid salt aqueous solution, stand-by；In connection
In benzoylformic acid saline solution, add 80% hydrazine hydrate 18.8g (0.19mol) and 15g sodium hydrate solids, be heated to 80 DEG C~
85 DEG C, 3h is incubated, then slowly heat temperature raising, 100 DEG C is raised in 2h, and 6h are incubated in 100 DEG C；Cooling reaction solution to 25 DEG C with
Under, beginning is slowly added dropwise hydrochloric acid, adjusts pH value, terminal is added dropwise and is counted with pH value as 3, and a large amount of white solids are separated out, and filtering, filter cake is used
Purifying water washing, is washed till filter liquor in neutrality, obtains felbinac crude product 29.3g, above crude product total recovery 76.8%.
Crude product isopropanol is refining to obtain felbinac fine work 24.9g, refines yield 85.1%.
Embodiment 2：
A kind of simple and convenient process for preparing of felbinac, comprises the following steps：
(1) preparation of 4-acetylbiphenyl hydrochlorate
In 300mL four-hole boiling flasks, nitrogen protection adds dichloroethanes 1080ml biphenyl 172.8g (1.08mol) and nothing
Water alchlor 230g (1.72mol), quick stirring is cooled to -4 DEG C, in dropwise addition ethyl oxalyl chloride 192g in 4 hours
(1.62mol), controls -3 DEG C of temperature~5 DEG C during dropwise addition；Drop finishes, and 9h is reacted in 0 DEG C, and reaction is complete to pour into dense salt by reaction solution
In acid/frozen water 3000mL, V (concentrated hydrochloric acid)/V (frozen water)=1.2：1；Stirring, point liquid, organic layer use saturated sodium-chloride water respectively
Solution, saturated sodium bicarbonate aqueous solution and purification of aqueous solutions are washed to neutrality to be finished, anhydrous sodium sulfate drying；Filtering, is evaporated off organic
Solvent, obtains compound 4-acetylbiphenyl acetoacetic ester；
(2) synthesis of felbinac
To 1mol/L NaOH solution 500mL are added in the compound obtained by step (1), it is stirred at room temperature 4 hours, has
A large amount of white sodium salts are separated out, and add 500mL water dissolves, after solid is completely dissolved, obtain 4-acetylbiphenyl acid salt aqueous solution, stand-by；
In 4-acetylbiphenyl acid salt aqueous solution, 85% hydrazine hydrate 122g (1.23mol) and 100g sodium hydrate solids are added, be heated to 80
DEG C~85 DEG C, 5h is incubated, then slowly heat temperature raising, 100 DEG C are raised in 4h, and 8h are incubated in 100 DEG C；Cool down reaction solution to 25
Below DEG C, beginning is slowly added dropwise hydrochloric acid, adjusts pH value, terminal is added dropwise and is counted with pH value as 3, and a large amount of white solids are separated out, filtering, filter
Cake purifying water washing, is washed till filter liquor in neutrality, obtains felbinac crude product 179g, above crude product total recovery 78.3%.
Crude product isopropanol is refining to obtain felbinac fine work 156.4g, refines yield 87.4%.
Comparative example 1：
A kind of simple and convenient process for preparing of felbinac, comprises the following steps：
(1) preparation of 4-acetylbiphenyl acetoacetic ester
In 500mL four-hole boiling flasks, nitrogen protection adds dichloroethanes 180ml biphenyl 27.8g (0.18mol) and anhydrous
Alchlor 36g (0.27mol), quick stirring is cooled to -5 DEG C, in dropwise addition ethyl oxalyl chloride 29.5g in 1 hour
(0.25mol), controls -5 DEG C of temperature~5 DEG C during dropwise addition.Drop finishes, and 6h is reacted in 0 DEG C, and reaction is finished pours into dense salt by reaction solution
In acid/frozen water 500mL, V (concentrated hydrochloric acid)/V (frozen water)=1：1；Stirring, point liquid, organic layer are water-soluble with saturated sodium-chloride respectively
Liquid, saturated sodium bicarbonate aqueous solution and purification of aqueous solutions are washed to neutrality to be finished, anhydrous sodium sulfate drying；Filtering, is evaporated off organic molten
Agent, obtains compound 4-acetylbiphenyl acetoacetic ester；
(2) preparation of 4-acetylbiphenyl hydrochlorate
To 1mol/L NaOH solution 80mL are added in the compound obtained by step (1), it is stirred at room temperature 2 hours, there is big
The white sodium salt of amount is separated out, filtering, filter cake purifying water washing, is washed till filter liquor in neutrality, and filter cake vacuum drying obtains 4-acetylbiphenyl
Hydrochlorate 35.6g, it is standby；
(3) synthesis of felbinac
To 80mL water in the compound obtained by step (2), is added, stirring adds 80% hydrazine hydrate 18.8g (0.19mol)
With 15g sodium hydrate solids, 80 DEG C~85 DEG C are heated to, are incubated 3h, then slowly heat temperature raising, be raised to 100 DEG C in 2h, and in
100 DEG C of insulation 6h；To less than 25 DEG C, beginning is slowly added dropwise hydrochloric acid to cooling reaction solution, adjusts pH value, dropwise addition terminal with pH value be 3
Meter, a large amount of white solids are separated out, filtering, filter cake purifying water washing, are washed till filter liquor in neutrality, obtain felbinac crude product
26.6g, above crude product total recovery 69.8%.
Crude product isopropanol is refining to obtain felbinac fine work 22.6g, refines yield 85.1%.
Preparation method and the preparation method gained yield of the embodiment of the present invention 1 that the intermediate of comparative example 1 is separate and operation
Cycle etc. is contrasted, as a result as follows：
The comparing result table of the comparative example 1 of table 1 and embodiment 1
| Packet | Yield | Operation cycle |
| Embodiment 1 | 76.8% | It is not required to filtering, direct next step operation |
| Comparative example 1 | 69.8% | Increase filtering, washing and drying process |
Conclusion：Increase intermediate to separate, increase filtering, washing and drying process, extend the operation cycle, increase people
Power, material resources and energy consumption, while cause unfriendly to surrounding environment, while filtering, washing can cause moiety intermediate to be lost,
Yield is relatively low.
Claims (9)
1. a kind of simple and convenient process for preparing of felbinac, it is characterised in that comprise the following steps：
(1) with biphenyl and ethyl oxalyl chloride as initial feed, there is Friedel-Crafts reaction under alchlor effect, in cryogenic conditions
Lower generation 4-acetylbiphenyl acetoacetic ester；
(2) alkaline hydrolysis is 4-acetylbiphenyl hydrochlorate, is acted on hydrazine in the basic conditions, is obtained through huang-Minlon reaction reduction, acidifying
Target compound felbinac；
2. the simple and convenient process for preparing of felbinac as claimed in claim 1, it is characterised in that the low temperature described in step (1)
It is -5~5 DEG C, more preferably -5~0 DEG C.
3. the simple and convenient process for preparing of felbinac as claimed in claim 1, it is characterised in that the reaction time is 6 in step (1)
~10h, more preferably 6h.
4. the simple and convenient process for preparing of felbinac as claimed in claim 1, it is characterised in that biphenyl used, grass in step (1)
Acyl chlorides mono ethyl ester is 1 with alchlor mol ratio:1~2:2, more preferably 1:1.2:2.
5. the simple and convenient process for preparing of felbinac as claimed in claim 1, it is characterised in that the alkali described in step (2) is
NaOH.
6. the simple and convenient process for preparing of felbinac as claimed in claim 1, it is characterised in that comprise the following steps：
(1) in four-hole boiling flask, nitrogen protection adds dichloroethanes 180ml, biphenyl 27.8g and aluminum trichloride (anhydrous) 36g, soon
Speed stirring is cooled to -5 DEG C, and in ethyl oxalyl chloride 29.5g is added dropwise in 1 hour, it is -5~5 DEG C that temperature is controlled during dropwise addition；Drop finishes,
6h~10h is reacted in 0 DEG C, reaction is finished pours into 500mL concentrated hydrochloric acid ice water solutions reaction solution, concentrated hydrochloric acid/frozen water volume
Than being 1~2：1；Stirring, point liquid, organic layer use saturated sodium-chloride water solution, saturated sodium bicarbonate aqueous solution and purifying respectively
Water washing to neutrality finishes, anhydrous sodium sulfate drying；Filtering, is evaporated off organic solvent, obtains compound 4-acetylbiphenyl acetoacetic ester；
(2) to 1mol/L NaOH solution 80mL are added in the compound obtained by step (1), it is stirred at room temperature 2-3 hours, has
A large amount of white sodium salts are separated out, and add 80mL water dissolves, after solid is completely dissolved, obtain 4-acetylbiphenyl acid salt aqueous solution, stand-by；
In 4-acetylbiphenyl acid salt aqueous solution, hydrazine hydrate 18.8g and the 15g sodium hydrate solid of mass concentration 75~85% is added, be heated to
80 DEG C~85 DEG C, 3-4h is incubated, then heat temperature raising, 100 DEG C is raised in 2h, and 6-8h is incubated in 100 DEG C；Cooling reaction solution is arrived
Less than 25 DEG C, start, hydrochloric acid is added dropwise, adjust pH value, terminal is added dropwise and is counted with pH value as 3, a large amount of white solids are separated out, filtering, filter
Cake purifying water washing, is washed till filter liquor in neutrality, obtains felbinac crude product；Crude product isopropanol is refining to obtain felbinac essence
Product.
7. the simple and convenient process for preparing of felbinac as claimed in claim 6, it is characterised in that the dense salt described in step (1)
Acid/frozen water volume ratio is 1:1.
8. the simple and convenient process for preparing of felbinac as claimed in claim 6, it is characterised in that the dropwise addition described in step (1)
It is -5 DEG C~0 DEG C that temperature is controlled during ethyl oxalyl chloride.
9. the simple and convenient process for preparing of felbinac as claimed in claim 6, it is characterised in that the hydration described in step (2)
The mass concentration concentration of hydrazine is 80%.
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109456177A (en) * | 2018-11-26 | 2019-03-12 | 深圳市第二人民医院 | The synthetic method of the bromo- 2- chlorobenzoyl chloride of Dapagliflozin intermediate 5- |
| CN110642669A (en) * | 2019-10-09 | 2020-01-03 | 上海博栋化学科技有限公司 | Preparation method of para-substituted bromobenzene |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101544561A (en) * | 2009-04-30 | 2009-09-30 | 江苏工业学院 | Preparation method of trifluoromethyl phenylacetic acid |
| CN103664536A (en) * | 2012-09-17 | 2014-03-26 | 天津科技大学 | Synthetic method of hydroxytyrosol |
-
2016
- 2016-12-22 CN CN201611196791.5A patent/CN106748770B/en active Active
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101544561A (en) * | 2009-04-30 | 2009-09-30 | 江苏工业学院 | Preparation method of trifluoromethyl phenylacetic acid |
| CN103664536A (en) * | 2012-09-17 | 2014-03-26 | 天津科技大学 | Synthetic method of hydroxytyrosol |
Non-Patent Citations (1)
| Title |
|---|
| F. F. BLICKE AND NATHANIEL GRIER: "Antispasmodics. V.", 《JOURNAL OF THE AMERICAN CHEMICAL SOCIETY》 * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109456177A (en) * | 2018-11-26 | 2019-03-12 | 深圳市第二人民医院 | The synthetic method of the bromo- 2- chlorobenzoyl chloride of Dapagliflozin intermediate 5- |
| CN110642669A (en) * | 2019-10-09 | 2020-01-03 | 上海博栋化学科技有限公司 | Preparation method of para-substituted bromobenzene |
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