CN106957237B - A method of synthesis bromfenac sodium - Google Patents
A method of synthesis bromfenac sodium Download PDFInfo
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- CN106957237B CN106957237B CN201710182240.1A CN201710182240A CN106957237B CN 106957237 B CN106957237 B CN 106957237B CN 201710182240 A CN201710182240 A CN 201710182240A CN 106957237 B CN106957237 B CN 106957237B
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C227/00—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton
- C07C227/22—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton from lactams, cyclic ketones or cyclic oximes, e.g. by reactions involving Beckmann rearrangement
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C231/00—Preparation of carboxylic acid amides
- C07C231/02—Preparation of carboxylic acid amides from carboxylic acids or from esters, anhydrides, or halides thereof by reaction with ammonia or amines
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/30—Indoles; Hydrogenated indoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to carbon atoms of the hetero ring
- C07D209/32—Oxygen atoms
- C07D209/34—Oxygen atoms in position 2
Abstract
The invention discloses a kind of methods for synthesizing bromfenac sodium, comprising steps of (1) obtains III: N-(2-(4'- bromophenyl acyl of formula using 2- amino -4'- bromine benzophenone as raw material, through acetylization reaction) phenyl) acetamide；(2) N-(2-(4'- bromophenyl acyl) phenyl) acetamide formula IV: halogen acetylation reagent reacts to obtain V: N- acetyl group-N-(2-(4'- bromophenyl acyl of formula) phenyl) -2- halogen acetamide；(3) N- acetyl group-N-(2-(4'- bromophenyl acyl) phenyl) -2- halogen acetamide obtains VI: 1- acetyl group -7-(4- bromo-benzoyl chloride of formula after friedel-crafts reaction) Indolin-2-one；(4) 1- acetyl group -7-(4- bromo-benzoyl chloride) Indolin-2-one finally hydrolyzes to obtain target product.The advantages that method of the invention is low in cost, reacts easily-controllable, and post-processing is simple, and overall yield is high, economic and environment-friendly, provides a kind of new method for synthesizing bromfenac sodium.
Description
Technical field
The present invention relates to medication chemistry field of medicaments, and specifically, invention is related to a kind of synthetic method of antalgesic, more specifically
For be it is a kind of synthesize bromfenac sodium new method.
Background technique
Bromfenac sodium (Bromfenac sodium), entitled [2- amino -3- (4- benzoyl bromide) phenyl] acetic acid of chemistry
Sodium；(2- amino -3- (4- Bromophenacyl) phenyl) sodium acetate, structure is similar with Ketoprofen and Diclofenac, epoxy can be inhibited to close
The synthesis for the prostanoid inflammatory mediator that enzyme mediates, is most effective cyclooxygenase-2 inhibitors, and there is strength anti-inflammatory analgesic to make
With.The compound is the quasi- non-steroidal anti-inflammatory drugs researched and developed by A.H.Ro bins company, the U.S., after patent right transferred into the U.S.
Wyeth-Ayers t company, with Japanese Senju company joint development, Senju company, Japan in 2000 is developed as Bromfenac
Sodium eye drops listed in Japan in 2 000 years, lists in the U.S. within 2005, is clinically used for treatment for outer eye and preceding eye
Diseases associated with inflammation symptomatic treatment: blepharitis, conjunctivitis, strong film scorching (including upper strong film is scorching), post-operation inflammatory etc., structural formula
It is as follows:
Patent EP221753 is disclosed with being starting material to Brominal and indoline, in alchlor and boron chloride
Catalysis under, carry out friedel-crafts reaction, then through aoxidizing, halogenation, sour water solution and basic hydrolysis obtain bromfenac sodium, and reaction equation is as follows:
In this method, starting material under the catalysis of alchlor and boron chloride, carries out Brominal and indoline
Friedel-crafts reaction, this step reaction is high to moisture requirement, generally requires just to can be carried out reaction after first carrying out point water, because of boron chloride
Explosive decomposition is instead given birth to after meeting water, potential risk limits its application in the industrial production significantly.
Document (journal of the American chemical society.1974 volume 95 5508~5517) mentions
It has supplied to carry out after reacting with t-butyl hypochlorate using 2- amino -4'- bromine benzophenone and 2- first ethyl thioglycolate as raw material
Replace cyclization, piptonychia sulfydryl, hydrolysis obtains bromfenac sodium, and reaction equation is as follows:
In this method, starting material 2- first ethyl thioglycolate has bad smell, and when use carries out protection and spy
Different processing, while 2- amino -4'- bromine benzophenone and 2- first ethyl thioglycolate are replaced under t-butyl hypochlorate catalysis
Cyclization needs to carry out (be lower than subzero 65 DEG C) under ultralow temperature, and subsequent piptonychia sulfydryl needs the Raney Ni in high activity, right
Safety in production has biggish threat, and disadvantages described above limits the application of the route in the industrial production.
Summary of the invention
The technical problem to be solved by the present invention is to overcome the defects of the prior art, provide a kind of side for synthesizing bromfenac sodium
Method, reagent is mild in this method, and reaction process is controllable, and post-processing is simple, high income, and economic and environment-friendly.
In order to solve the above technical problems, the technical solution adopted by the present invention is that:
A method of synthesis bromfenac sodium, comprising the following steps:
(1) II: 2- amino -4'- bromine benzophenone of formula obtains formula III through acetylization reaction；
(2) formula III is with formula IV: halogen acetylation reagent reacts to obtain formula V；
Wherein: X is selected from Cl or Br；
(3) formula V obtains formula VI after friedel-crafts reaction；
(4) bromfenac sodium is obtained after hydrolyzing.
Preferably, formula IV, i.e. halogen acetylation reagent are chloracetyl chloride, bromoacetyl bromide, chloroacetic anhydride, bromoacetic acid acid anhydride.
Preferably, in step (1): formula II is dissolved in solvent A, and introduces organic base A；Preferably, reaction temperature be 0~
90 DEG C, reaction temperature is more preferably 0~50 DEG C.Preferred solvent A is selected from methylene chloride, toluene, 2- methyltetrahydrofuran
One of or more than one mixture.Preferred acetylation reagent in acetylization reaction are as follows: chloroacetic chloride or/and acetic anhydride.
Preferably, the molar ratio of formula II and acetylation reagent dosage is 1:1.01~1:1.5, further preferably 1:1.01~1:1.2.
Preferred organic base A is triethylamine or/and diisopropylethylamine.Preferably, the molar ratio of organic base A and acetylation reagent dosage
For 1:1~1.5:1, further preferably 1:1~1.2:1.
Preferably, the post-processing approach reacted in step (1) includes: that organic phase is washed with water at least once after reacting,
Then dry, concentration.
Preferably, in step (2): formula III is dissolved in solvent B, and introduces organic base B and catalyst B.Preferred reaction temperature
Degree is 50~120 DEG C；Further preferably 70~120 DEG C.Preferred solvent B is toluene or/and chloroform.Formula V is rubbed with formula IV
You are than 1:1.01~1:2, further preferably 1:1.1~1:1.5.Preferred organic base B is triethylamine or/and diisopropyl second
Amine.The dosage of preferred organic base B and the molar ratio of formula IV are 1:1~1.5:1, further preferably 1:1~1.2:1.Catalysis
Agent B is selected as 4-dimethylaminopyridine, and the molar ratio of preferred catalyst B and formula IV is 0.1:1~1:1, further preferably
0.3:1~1:1.
Preferably, the post-processing approach reacted in step (2) includes: that organic phase is washed with water at least once after reacting,
Then dry, concentration.
Preferably, in step (3): formula V is dissolved in solvent C, and introduces catalyst C.Preferred catalyst is lewis acid
Catalyst, further preferably are as follows: alchlor, ferric trichloride, one of zinc chloride or more than one mixture, more into one
Step is preferably alchlor or ferric trichloride.Preferred reaction temperature is 50~150 DEG C, further preferably 70~120 DEG C.It is excellent
The solvent C of choosing is chloroform or/and chlorobenzene.Molar ratio 1:1~3:1 of preferred catalyst C and formula V, further preferably 1.3:
1~2:1.
Preferably, the post-processing approach reacted in step (3) includes recrystallization, further preferably are as follows: will reaction after reaction
Mixed liquor is added drop-wise in ice water, and filtering is collected filter cake, finally recrystallized.
Preferably, in step (4): formula VI is dissolved in solvent D, and introduces catalyst D.Preferred reaction temperature is 50~100
DEG C, further preferably 70~100 DEG C.Preferred solvent D is selected from ethyl alcohol, isopropanol, one of water or more than one is mixed
Close object.Preferred catalyst D is sodium hydroxide.Molar ratio 2.1:1~10:1 of preferred catalyst D and formula VI, it is further excellent
It is selected as 4:1~10:1.
Preferably, the post-processing approach reacted in step (4) includes recrystallization, further preferably are as follows: will reaction after reaction
Mixed liquor is added drop-wise in methyl tertiary butyl ether(MTBE) (the also known as tertiary ether of first, abridge MTBE), and filtering is collected filter cake, finally recrystallized.
Preferably, bromfenac sodium obtained by step (4) includes the crystalline hydrate of type I compound or/and type I compound:
Wherein, the crystalline hydrate of type I compound includes following VII compound of formula:
Advantageous effects of the invention:
For compared with the prior art, method of the invention is low in cost, reacts easily-controllable, and post-processing is simple, and overall yield is high,
Overall yield is economic and environment-friendly between 46%-60%, provides a kind of new method for synthesizing bromfenac sodium.
Detailed description of the invention
Fig. 1 is the synthesis general line figure of bromfenac sodium in embodiment.
Specific embodiment
The invention will be further described below in conjunction with the accompanying drawings.Following embodiment is only used for clearly illustrating the present invention
Technical solution, and not intended to limit the protection scope of the present invention.
In the present invention, if without specified otherwise, used solvent (including solvent A, solvent B, solvent C, solvent D), reagent (packet
Include various catalyst, acetylation reagent and halogen acetylation reagent) etc. be that routine business means are commercially available, be not necessarily to special place
Reason.If all chemical reagent used in the present invention are to its purity without particular/special requirement, the pure grade of chemistry or purity without specified otherwise
Higher analysis is pure, excellent pure grade is ok.But preferably with high purity.
Embodiment 1
(1) preparation of N- (2- (4'- bromophenyl acyl) phenyl) acetamide (formula III)
414g 2- amino -4'- bromine benzophenone (formula II) and 150g triethylamine are added to 2.5L 2- methyltetrahydrofuran
In, 0~20 DEG C of temperature control, it is added dropwise to 94g chloroacetic chloride, to fully reacting, organic phase washing and drying is concentrated to get N- for stirring after addition
(2- (4'- bromophenyl acyl) phenyl) acetamide 470g, yield 98.5%.
(2) N- acetyl group-N- (2- (4'- bromophenyl acyl) phenyl) -2- acetbromamide (formula V).Wherein X be Br) system
It is standby:
Take 450gN- (2- (4'- bromophenyl acyl) phenyl) acetamide, 220g diisopropylethylamine and 22g4- dimethylamino pyrrole
Pyridine is added in the toluene of 5L, 280g bromoacetyl bromide is added dropwise, after being added dropwise, 90~100 DEG C of temperature control, to fully reacting, are down to room
Wen Hou, organic phase are washed with water, dry, and recycling organic solvent is concentrated under reduced pressure, obtains 560g N- acetyl group-N- (2- (4'- bromobenzene acyl
Base) phenyl) -2- acetbromamide, yield 90.1%.
3) preparation of 1- acetyl group -7- (4- bromo-benzoyl chloride) Indolin-2-one (formula VI)
500g N- acetyl group-N- (2- (4'- bromophenyl acyl) phenyl) -2- acetbromamide is taken to be added in the chlorobenzene of 2L, point
It criticizes and 200g alchlor is added, 100~110 DEG C are warming up to after adding to fully reacting, is added drop-wise to reaction solution after fully reacting
In ice water, filter cake is collected by filtration, filtration cakes torrefaction obtains crude product, and crude product obtains 329g1- acetyl group -7- through re-crystallizing in ethyl acetate
(4- bromo-benzoyl chloride) Indolin-2-one, yield 80.2%.
4) preparation of bromfenac sodium
300g 1- acetyl group -7- (4- bromo-benzoyl chloride) Indolin-2-one is taken to be added to 800mL methanol and 200ml water
In, 120g sodium hydroxide is added portionwise, 60~70 DEG C are warming up to after adding to fully reacting, reaction solution is added dropwise after fully reacting
Into the tertiary ether of 3L first, filter cake is collected by filtration, filtration cakes torrefaction obtains crude product, and crude product is recrystallized to give 239.9g bromfenac sodium, receives
Rate 80.5%, purity 99.67%,1HNMR(d6-DMSO)δ:7.95-7.80(s,2H),7.75-7.60(d,2H,J 8Hz),
7.55-7.40 (d, 2H, J8Hz), 7.15-6.95 (dd, 2H), 6.48-6.35 (t, 1H), 3.2 (s, 2H).
Embodiment 2
(1) preparation of N- (2- (4'- bromophenyl acyl) phenyl) acetamide
700g 2- amino -4'- bromine benzophenone and 425g diisopropylethylamine are added in 5L methylene chloride, are added dropwise to
300g acetic anhydride, to fully reacting, organic phase washing and drying is concentrated to get N- (2- (4'- bromophenyl acyl) phenyl) for stirring after addition
Acetamide 766g, yield 95%.
(2) preparation of N- acetyl group-N- (2- (4'- bromophenyl acyl) phenyl) -2- acetbromamide
750gN- (2- (4'- bromophenyl acyl) phenyl) acetamide is taken, 357g triethylamine and 35g4- dimethylamino naphthyridine are added
Into the toluene of 10L, 675g bromoacetic acid acid anhydride is added dropwise, after being added dropwise, temperature rising reflux to fully reacting is cooled to room temperature, organic
Mutually it is washed with water, it is dry, recycling organic solvent is concentrated under reduced pressure, obtains 955g N- acetyl group-N- (2- (4'- bromophenyl acyl) phenyl)-
2- acetbromamide, yield 92.3%.
3) preparation of 1- acetyl group -7- (4- bromo-benzoyl chloride) Indolin-2-one
900g N- acetyl group-N- (2- (4'- bromophenyl acyl) phenyl) -2- acetbromamide is taken to be added in the chloroform of 5L, point
It criticizes and 550g alchlor is added, add rear temperature rising reflux to fully reacting, reaction solution is added drop-wise in ice water after fully reacting, mistake
Filter cake is collected in filter, and filtration cakes torrefaction obtains crude product, and crude product obtains 559g1- acetyl group -7- (4- bromobenzene first through re-crystallizing in ethyl acetate
Acyl chlorides) Indolin-2-one, yield 76.2%.
4) preparation of bromfenac sodium
300g 1- acetyl group -7- (4- bromo-benzoyl chloride) Indolin-2-one is taken to be added to 900mL ethyl alcohol and 250ml water
In, 130g sodium hydroxide is added portionwise, 70~80 DEG C are warming up to after adding to fully reacting, reaction solution is added dropwise after fully reacting
Into the tertiary ether of 3L first, filter cake is collected by filtration, filtration cakes torrefaction obtains crude product, and crude product is recrystallized to give 249.8g bromfenac sodium, receives
Rate 83.5%, purity 99.74%,1HNMR(d6-DMSO)δ:7.95-7.80(s,2H),7.75-7.60(d,2H,J 8Hz),
7.55-7.40 (d, 2H, J8Hz), 7.15-6.95 (dd, 2H), 6.48-6.35 (t, 1H), 3.2 (s, 2H).
Embodiment 3
(1) preparation of N- (2- (4'- bromophenyl acyl) phenyl) acetamide
500g 2- amino -4'- bromine benzophenone and 300g diisopropylethylamine are added in 5L toluene, temperature control 10~20
DEG C, it is added dropwise to 170g chloroacetic chloride, to fully reacting, organic phase washing and drying is concentrated to get N- (2- for heating stirring naturally after addition
(4'- bromophenyl acyl) phenyl) acetamide 543g, yield 94.3%.
(2) preparation of N- acetyl group-N- (2- (4'- bromophenyl acyl) phenyl) -2- chloroacetamide
510gN- (2- (4'- bromophenyl acyl) phenyl) acetamide is taken, 320g triethylamine and 50g4- dimethylamino naphthyridine are added
Into the toluene of 5L, 270g chloracetyl chloride is added dropwise, after being added dropwise, 100~110 DEG C of temperature control to fully reacting is cooled to room temperature,
Organic phase is washed with water, dry, and recycling organic solvent is concentrated under reduced pressure, obtains 552g N- acetyl group-N- (2- (4'- bromophenyl acyl) benzene
Base) -2- chloroacetamide, yield 87.5%.
3) preparation of 1- acetyl group -7- (4- bromo-benzoyl chloride) Indolin-2-one
500g N- acetyl group-N- (2- (4'- bromophenyl acyl) phenyl) -2- chloroacetamide is taken to be added in the chlorobenzene of 2L, point
It criticizes and 330g alchlor is added, 100~110 DEG C are warming up to after adding to fully reacting, is added drop-wise to reaction solution after fully reacting
In ice water, filter cake is collected by filtration, filtration cakes torrefaction obtains crude product, and crude product obtains 343.7g1- acetyl group-through re-crystallizing in ethyl acetate
7- (4- bromo-benzoyl chloride) Indolin-2-one, yield 76.2%.
4) preparation of bromfenac sodium
300g 1- acetyl group -7- (4- bromo-benzoyl chloride) Indolin-2-one is taken to be added to 750mL isopropanol and 300ml
In water, 150g sodium hydroxide is added portionwise, 70~80 DEG C are warming up to after adding to fully reacting, drop will be reacted after fully reacting
It being added in the tertiary ether of 3L first, filter cake is collected by filtration, filtration cakes torrefaction obtains crude product, and crude product is recrystallized to give 257.8g bromfenac sodium,
Yield 86.5%, purity 99.47%,1HNMR(d6-DMSO)δ:7.95-7.80(s,2H),7.75-7.60(d,2H,J 8Hz),
7.55-7.40 (d, 2H, J8Hz), 7.15-6.95 (dd, 2H), 6.48-6.35 (t, 1H), 3.2 (s, 2H).
Embodiment 4
(1) preparation of N- (2- (4'- bromophenyl acyl) phenyl) acetamide
500g 2- amino -4'- bromine benzophenone and 300g diisopropylethylamine are added in 5L toluene, temperature control 10~20
DEG C, it is added dropwise to 170g chloroacetic chloride, to fully reacting, organic phase washing and drying is concentrated to get N- (2- for heating stirring naturally after addition
(4'- bromophenyl acyl) phenyl) acetamide 543g, yield 94.3%.
(2) preparation of N- acetyl group-N- (2- (4'- bromophenyl acyl) phenyl) -2- chloroacetamide
Take 510gN- (2- (4'- bromophenyl acyl) phenyl) acetamide, 410g diisopropylethylamine and 60g4- dimethylamino pyrrole
Pyridine is added in the toluene of 5L, 490g chloroacetic anhydride is added dropwise, after being added dropwise, 100~110 DEG C of temperature control, to fully reacting, are down to
After room temperature, organic phase is washed with water, dry, and recycling organic solvent is concentrated under reduced pressure, obtains 526g N- acetyl group-N- (2- (4'- bromobenzene
Acyl group) phenyl) -2- chloroacetamide, yield 83.5%.
3) preparation of 1- acetyl group -7- (4- bromo-benzoyl chloride) Indolin-2-one
500g N- acetyl group-N- (2- (4'- bromophenyl acyl) phenyl) -2- chloroacetamide is taken to be added in the chlorobenzene of 2L, point
It criticizes and 350g ferric trichloride is added, 100~110 DEG C are warming up to after adding to fully reacting, is added drop-wise to reaction solution after fully reacting
In ice water, filter cake is collected by filtration, filtration cakes torrefaction obtains crude product, and crude product obtains 316.7g1- acetyl group-through re-crystallizing in ethyl acetate
7- (4- bromo-benzoyl chloride) Indolin-2-one, yield 70.2%.
4) preparation of bromfenac sodium
300g 1- acetyl group -7- (4- bromo-benzoyl chloride) Indolin-2-one is taken to be added to 500ml methanol 500ml ethyl alcohol
In 400ml water, 180g sodium hydroxide is added portionwise, 60~70 DEG C are warming up to after adding to fully reacting, is incited somebody to action after fully reacting
Reaction solution is added drop-wise in the tertiary ether of 3L first, and filter cake is collected by filtration, and filtration cakes torrefaction obtains crude product, and crude product is recrystallized to give 248.8g bromine
Fragrant acid sodium, yield 83.5%, purity 99.47%,1HNMR(d6-DMSO)δ:7.95-7.80(s,2H),7.75-7.60(d,2H,J
8Hz), 7.55-7.40 (d, 2H, J 8Hz), 7.15-6.95 (dd, 2H), 6.48-6.35 (t, 1H), 3.2 (s, 2H).
The above is only a preferred embodiment of the present invention, it is noted that for the ordinary skill people of the art
For member, without departing from the technical principles of the invention, several improvement and deformations can also be made, these improvement and deformations
Also it should be regarded as protection scope of the present invention.
Claims (8)
1. a kind of method for synthesizing bromfenac sodium, which comprises the following steps:
(1) II: 2- amino -4'- bromine benzophenone of formula obtains formula III through acetylization reaction；
(2) formula III is with formula IV: halogen acetylation reagent reacts to obtain formula V；
Wherein: X is selected from Cl or Br；
(3) formula V obtains formula VI after friedel-crafts reaction；
(4) bromfenac sodium is obtained after hydrolyzing；
In step (1): formula II is dissolved in solvent A, and introduces organic base A；In step (2): formula III is dissolved in solvent B, and is introduced
Organic base B and catalyst B；In step (3): formula V is dissolved in solvent C, and introduces catalyst C；In step (4): formula VI is dissolved in molten
Agent D, and introduce catalyst D.
It is 0~90 DEG C that reaction temperature, which is reaction temperature, in step (1)；Reaction temperature is 50~120 DEG C in step (2)；Step (3)
Middle reaction temperature is 50~150 DEG C, and reaction temperature is 50~100 DEG C in step (4).
2. a kind of method for synthesizing bromfenac sodium according to claim 1, which is characterized in that catalyst B are as follows: 4- diformazan ammonia
Yl pyridines, catalyst C are lewis acid catalyst, and catalyst D is sodium hydroxide.
3. a kind of method for synthesizing bromfenac sodium according to claim 1 to 2, which is characterized in that in step (1): solvent A
It is chloroacetic chloride selected from one of methylene chloride, toluene, 2- methyltetrahydrofuran or more than one mixture, acetylation reagent
Or/and acetic anhydride, the molar ratio of formula II and acetylation reagent dosage are 1:1.01~1:1.5；Organic base A be triethylamine or/and
Diisopropylethylamine；The molar ratio of organic base A and acetylation reagent dosage is 1:1~1.5:1.
4. a kind of method for synthesizing bromfenac sodium according to claim 1 to 2, which is characterized in that in step (2): solvent B
For toluene or/and chloroform, molar ratio 1:1.01~1:2 of formula V and formula IV；Organic base B is triethylamine or/and diisopropyl second
Amine；The dosage of organic base B and the molar ratio of formula IV are 1:1~1.5:1；The molar ratio of catalyst B and formula IV is 0.1:1~1:1.
5. a kind of method for synthesizing bromfenac sodium according to claim 1 to 2, which is characterized in that in step (3): solvent C
For chloroform or/and chlorobenzene, molar ratio 1:1~3:1 of catalyst C and formula V.
6. a kind of method for synthesizing bromfenac sodium according to claim 1 to 2, which is characterized in that in step (4): solvent D
Selected from ethyl alcohol, isopropanol, one of water or more than one mixture, molar ratio 2.1:1~10 of catalyst D and formula VI:
1。
7. a kind of method for synthesizing bromfenac sodium according to claim 1 to 2, which is characterized in that catalyst C is selected from trichlorine
Change aluminium, ferric trichloride, one of zinc chloride or more than one mixture.
8. a kind of method for synthesizing bromfenac sodium according to claim 1, which is characterized in that Bromfenac obtained by step (4)
Sodium includes the crystalline hydrate of type I compound or/and type I compound:
。
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