CN106008195A - Preparation method of 2,4-difluoro-5-iodobenzoic acid - Google Patents
Preparation method of 2,4-difluoro-5-iodobenzoic acid Download PDFInfo
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- CN106008195A CN106008195A CN201610332600.7A CN201610332600A CN106008195A CN 106008195 A CN106008195 A CN 106008195A CN 201610332600 A CN201610332600 A CN 201610332600A CN 106008195 A CN106008195 A CN 106008195A
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- OSBABFNFGBPWGL-UHFFFAOYSA-N 2,4-difluoro-5-iodobenzoic acid Chemical compound OC(=O)C1=CC(I)=C(F)C=C1F OSBABFNFGBPWGL-UHFFFAOYSA-N 0.000 title claims abstract description 15
- 238000002360 preparation method Methods 0.000 title claims abstract description 15
- VTIIJXUACCWYHX-UHFFFAOYSA-L disodium;carboxylatooxy carbonate Chemical compound [Na+].[Na+].[O-]C(=O)OOC([O-])=O VTIIJXUACCWYHX-UHFFFAOYSA-L 0.000 claims abstract description 16
- 229940045872 sodium percarbonate Drugs 0.000 claims abstract description 16
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims abstract description 13
- 239000011630 iodine Substances 0.000 claims abstract description 13
- 229910052740 iodine Inorganic materials 0.000 claims abstract description 13
- 239000003153 chemical reaction reagent Substances 0.000 claims abstract description 3
- 238000006243 chemical reaction Methods 0.000 claims description 35
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 9
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 claims description 9
- 239000001117 sulphuric acid Substances 0.000 claims description 9
- 235000011149 sulphuric acid Nutrition 0.000 claims description 9
- 239000002253 acid Substances 0.000 claims description 7
- HTVMXJUPTRXRRN-UHFFFAOYSA-N C(=O)O.FC1=CC=CC(=C1)F Chemical compound C(=O)O.FC1=CC=CC(=C1)F HTVMXJUPTRXRRN-UHFFFAOYSA-N 0.000 claims description 6
- 125000002346 iodo group Chemical group I* 0.000 claims description 6
- 150000002978 peroxides Chemical class 0.000 claims description 6
- 230000000977 initiatory effect Effects 0.000 claims description 2
- 239000000463 material Substances 0.000 claims description 2
- AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical class [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 claims description 2
- 238000000034 method Methods 0.000 abstract description 8
- 238000006192 iodination reaction Methods 0.000 abstract 2
- NJYBIFYEWYWYAN-UHFFFAOYSA-N 2,4-difluorobenzoic acid Chemical compound OC(=O)C1=CC=C(F)C=C1F NJYBIFYEWYWYAN-UHFFFAOYSA-N 0.000 abstract 1
- 230000002378 acidificating effect Effects 0.000 abstract 1
- 238000009776 industrial production Methods 0.000 abstract 1
- 230000026045 iodination Effects 0.000 abstract 1
- 239000007858 starting material Substances 0.000 abstract 1
- 238000003756 stirring Methods 0.000 description 12
- 239000000376 reactant Substances 0.000 description 9
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 8
- 241000725303 Human immunodeficiency virus Species 0.000 description 6
- JQWHASGSAFIOCM-UHFFFAOYSA-M sodium periodate Chemical compound [Na+].[O-]I(=O)(=O)=O JQWHASGSAFIOCM-UHFFFAOYSA-M 0.000 description 6
- 230000015572 biosynthetic process Effects 0.000 description 5
- 238000003786 synthesis reaction Methods 0.000 description 5
- 208000030507 AIDS Diseases 0.000 description 4
- LQZMLBORDGWNPD-UHFFFAOYSA-N N-iodosuccinimide Chemical compound IN1C(=O)CCC1=O LQZMLBORDGWNPD-UHFFFAOYSA-N 0.000 description 4
- 229960000583 acetic acid Drugs 0.000 description 4
- 238000001816 cooling Methods 0.000 description 4
- 230000007613 environmental effect Effects 0.000 description 4
- 238000001914 filtration Methods 0.000 description 4
- 239000012362 glacial acetic acid Substances 0.000 description 4
- 238000012544 monitoring process Methods 0.000 description 4
- 239000007800 oxidant agent Substances 0.000 description 4
- 238000010792 warming Methods 0.000 description 4
- 238000005406 washing Methods 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
- 239000007864 aqueous solution Substances 0.000 description 3
- 230000000052 comparative effect Effects 0.000 description 3
- 238000007796 conventional method Methods 0.000 description 3
- 238000011161 development Methods 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- 238000007336 electrophilic substitution reaction Methods 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 3
- NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 2
- 150000002500 ions Chemical class 0.000 description 2
- NUJOXMJBOLGQSY-UHFFFAOYSA-N manganese dioxide Chemical compound O=[Mn]=O NUJOXMJBOLGQSY-UHFFFAOYSA-N 0.000 description 2
- 230000010534 mechanism of action Effects 0.000 description 2
- 230000001590 oxidative effect Effects 0.000 description 2
- 238000012805 post-processing Methods 0.000 description 2
- 150000007660 quinolones Chemical class 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical compound [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- 238000005160 1H NMR spectroscopy Methods 0.000 description 1
- 229940124321 AIDS medicine Drugs 0.000 description 1
- 229940126656 GS-4224 Drugs 0.000 description 1
- 229940126154 HIV entry inhibitor Drugs 0.000 description 1
- 229940099797 HIV integrase inhibitor Drugs 0.000 description 1
- AFCARXCZXQIEQB-UHFFFAOYSA-N N-[3-oxo-3-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)propyl]-2-[[3-(trifluoromethoxy)phenyl]methylamino]pyrimidine-5-carboxamide Chemical compound O=C(CCNC(=O)C=1C=NC(=NC=1)NCC1=CC(=CC=C1)OC(F)(F)F)N1CC2=C(CC1)NN=N2 AFCARXCZXQIEQB-UHFFFAOYSA-N 0.000 description 1
- 238000005481 NMR spectroscopy Methods 0.000 description 1
- 244000061176 Nicotiana tabacum Species 0.000 description 1
- 235000002637 Nicotiana tabacum Nutrition 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 210000001744 T-lymphocyte Anatomy 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 125000004429 atom Chemical group 0.000 description 1
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
- KRVSOGSZCMJSLX-UHFFFAOYSA-L chromic acid Substances O[Cr](O)(=O)=O KRVSOGSZCMJSLX-UHFFFAOYSA-L 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- JUZYLCPPVHEVSV-LJQANCHMSA-N elvitegravir Chemical compound COC1=CC=2N([C@H](CO)C(C)C)C=C(C(O)=O)C(=O)C=2C=C1CC1=CC=CC(Cl)=C1F JUZYLCPPVHEVSV-LJQANCHMSA-N 0.000 description 1
- 229960003586 elvitegravir Drugs 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- AWJWCTOOIBYHON-UHFFFAOYSA-N furo[3,4-b]pyrazine-5,7-dione Chemical compound C1=CN=C2C(=O)OC(=O)C2=N1 AWJWCTOOIBYHON-UHFFFAOYSA-N 0.000 description 1
- 229910052736 halogen Inorganic materials 0.000 description 1
- 150000002367 halogens Chemical group 0.000 description 1
- 239000002835 hiv fusion inhibitor Substances 0.000 description 1
- 239000003084 hiv integrase inhibitor Substances 0.000 description 1
- 230000001771 impaired effect Effects 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 229940124524 integrase inhibitor Drugs 0.000 description 1
- 239000002850 integrase inhibitor Substances 0.000 description 1
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
- 229910000450 iodine oxide Inorganic materials 0.000 description 1
- AFSVSXMRDKPOEW-UHFFFAOYSA-N oxidoiodine(.) Chemical compound I[O] AFSVSXMRDKPOEW-UHFFFAOYSA-N 0.000 description 1
- 239000012264 purified product Substances 0.000 description 1
- 229960004742 raltegravir Drugs 0.000 description 1
- CZFFBEXEKNGXKS-UHFFFAOYSA-N raltegravir Chemical compound O1C(C)=NN=C1C(=O)NC(C)(C)C1=NC(C(=O)NCC=2C=CC(F)=CC=2)=C(O)C(=O)N1C CZFFBEXEKNGXKS-UHFFFAOYSA-N 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 238000012827 research and development Methods 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 235000010265 sodium sulphite Nutrition 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 229940070590 stribild Drugs 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C51/00—Preparation of carboxylic acids or their salts, halides or anhydrides
- C07C51/347—Preparation of carboxylic acids or their salts, halides or anhydrides by reactions not involving formation of carboxyl groups
- C07C51/363—Preparation of carboxylic acids or their salts, halides or anhydrides by reactions not involving formation of carboxyl groups by introduction of halogen; by substitution of halogen atoms by other halogen atoms
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Engineering & Computer Science (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention discloses a preparation method of 2,4-difluoro-5-iodobenzoic acid. 2,4-difluorobenzoic acid is taken as a starting material, sodium percarbonate and elemental iodine are taken as green iodination reagents, a mild iodination reaction is performed under an acidic condition, and a high-purity target product is obtained. The synthetic process is environment-friendly and suitable for large-scale industrial production, and aftertreatment is convenient.
Description
Technical field:
The invention belongs to technical field of medicine synthesis, specifically refer to a kind of 2, the preparation method of 4-bis-fluoro-5-iodo-benzoic acid.
Background technology:
Acquired immune deficiency syndrome (AIDS) (AIDS) is to be infected, by HIV (human immunodeficiency virus) (HIV), the class fatal disease causing T-cell immune system impaired and to cause, at present, HIV person has presented the trend quickly spread, and whole world HIV sufferers case fatality rate has reached more than 60%.Along with the research of inhibition of HIV and course of infection thereof is deepened continuously by the mankind, and being continually striving to of various countries medicament research and development personnel, inverase has had the development advanced by leaps and bounds, the HIV entry inhibitor of especially brand-new mechanism of action and the appearance of hiv integrase inhibitor, development for inverase indicates new development direction, also brings new hope for treating AIDS.
Angstrom for lattice Wei (Elvitegravir) be by Japan Tobacco company develop, Gilead Sciences company of the U.S. exploitation quinolones inverase, trade name Stribild, structural formula is as shown in Equation 1.Angstrom for lattice Wei be an integrase inhibitor, be to be developed by keto-enol acid compounds, and the Merck (Raltegravir) of Merck have the same mechanism of action, is the anti-AIDS drug of first quinolones.
2,4-bis-fluoro-5-iodo-benzoic acids are the synthetic drug angstrom crucial intermediate for lattice Wei.The method synthesizing iodo product 2 at present in patent is all from the beginning of carboxylic acid 1, obtains, and NIS is to water sensitive after N-N-iodosuccinimide (NIS) iodide reaction, and price comparison is expensive.
At present, the industrial conventional method carrying out iodo on phenyl ring mainly has three classes, the first kind is by halogen exchange method, Equations of The Second Kind is that aniline is through diazotising iodo, both approaches is required on phenyl ring the functional group having activation on specific position, the most whether the difficulty that raw material still reacts is all expensive than the method carrying out iodo with NIS, 3rd class is the method using iodine oxide generation, this kind of method typically requires a kind of strong oxidant such as sodium metaperiodate, chromic acid and manganese dioxide etc., owing to the 3rd class reaction is electrophilic substitution reaction, therefore for the phenyl ring of electron deficiency, iodide reaction is the most difficult, and this type of oxidant can produce substantial amounts of useless miscellaneous, it not green, the reaction of atom economy type.
Summary of the invention:
The problems referred to above existed for prior art, it is an object of the invention to design provides a kind of reaction process environmental protection, productivity is high simultaneously, post processing is simple, production cost is low 2, the preparation method of 4-bis-fluoro-5-iodo-benzoic acid.
The technical scheme that the present invention takes is as follows:
A kind of 2, the preparation method of 4-bis-fluoro-5-iodo-benzoic acid, it is characterised in that: with 2,4 difluorobenzene formic acid as initiation material, SODIUM PERCARBONATE and iodine are green iodo reagent, carry out iodide reaction in acid condition, obtain 2,4-bis-fluoro-5-iodo-benzoic acid.
Further it is provided that
Described reaction temperature is preferably 45-50 DEG C；
The amount of described concentrated sulphuric acid is preferably 48-60ml；
The temperature during dropping of described concentrated sulphuric acid is 0-10 DEG C；
Described iodine is 1:0.32～1 with the reaction ratio of SODIUM PERCARBONATE；
Particularly preferred, when reaction temperature is 50 DEG C, and the usage amount of concentrated sulphuric acid is 53.30ml, when the mol ratio of iodine and SODIUM PERCARBONATE is 1:0.50, the productivity of iodide reaction is the highest, reaches 88%.
After having reacted, remove the peroxide of excess with saturated sodium thiosulfate.
The reaction equation that the present invention relates to is as follows:
The method have the advantages that
1, in the present invention, iodine reacts generation I in acid condition with SODIUM PERCARBONATE+Ion.Carrying out electrophilic substitution reaction the most again, eliminate the oxidants such as sodium metaperiodate in conventional method, therefore reaction system compares environmental protection.
2, the temperature of reaction is gentle.
3, the post processing of reaction is simple: the product reacted directly separates out in water, filters, and washing i.e. can obtain highly purified product.
4, yield is high: and preferable reaction temperature and response time, it is possible to obtain preferably productivity, reach as high as more than 78%.
To sum up: use the synthetic method of the present invention, on the one hand can make the preparation technology more environmental protection of entirety, be more suitable for industrialized production, on the other hand, the present invention can obtain the target product of good yield and purity, has prominent effect and economic worth.
Below in conjunction with the drawings and specific embodiments, the invention will be further described.
Accompanying drawing illustrates:
Fig. 1 is that the embodiment of the present invention prepares 2,4-bis-fluoro-5-iodo-benzoic acid (1H NMR, 400M, solvent C DCl3) nuclear magnetic resonance map.
Detailed description of the invention:
Embodiment 1:
By glacial acetic acid 60ml, I25.33g (21mmol) joins in the there-necked flask of 250ml, under stirring at room temperature, is slowly dividedly in some parts SODIUM PERCARBONATE 4.20g (containing 31mmolH in 20-30 minute2O2), increase the temperature to 35 DEG C under stirring, add 2,4 difluorobenzene formic acid 6.32g (40mmol).Cooling reactant liquor to 10 DEG C, the quickly lower 98%H dripping 53.30ml of stirring2SO4, it is warming up to 45 DEG C after adding and reacts 2.5 hours, point sample monitoring reaction end.After having reacted, cool down reactant liquor, whether also having oxide with in potassium iodide starch test paper detection reactant liquor, if having, then using Na2SO3Aqueous solution (10g sodium sulfite is dissolved in 500ml water, and configuration quality mark is the solution of 2%) removes peroxide.Then sucking filtration, with distilled water wash 1 time, obtains 2, and 4-bis-fluoro-5-iodo-benzoic acid, productivity is 76%.Fusing point: 150～153 DEG C.
Alternative 1-11
Preparation method is with embodiment 1, and difference is, adjusts the reaction ratio etc. of reaction temperature, the amount of concentrated sulphuric acid, iodine and SODIUM PERCARBONATE, and tests its impact on reaction respectively.
Table 1
As shown in table 1: 2, in the synthesis of 4-bis-fluoro-5-iodo-benzoic acid, reaction temperature, the amount of concentrated sulphuric acid, iodine has considerable influence with the reaction ratio of SODIUM PERCARBONATE to the productivity of reaction, it can be seen that work as the 2 of 40mmol from data, 4-difluoro-benzoic acid is 50 DEG C in reaction temperature, the usage amount of concentrated sulphuric acid is 53.30ml, and when the mol ratio of iodine and SODIUM PERCARBONATE is 1:0.50, the productivity of iodide reaction is the highest.
Comparative example 1:
By glacial acetic acid 80ml, acetic anhydride 50ml, I25.58g (22mmol) joins in the there-necked flask of 250ml, under stirring at room temperature, is slowly dividedly in some parts under SODIUM PERCARBONATE 12.5g, stirring and increases the temperature to 35 DEG C in 20-30 minute, adds 2,4 difluorobenzene formic acid 6.32g (40mmol).Cooling reactant liquor to 10 DEG C, the quickly lower 98%H dripping 36ml of stirring2SO4, it is warming up to 50 DEG C after adding and reacts 2 hours, point sample monitoring reaction end.After having reacted, cool down reactant liquor, remove peroxide.Then sucking filtration, washing, obtain 2,4-bis-fluoro-5-iodo-benzoic acid, productivity is 64%.
Comparative example 2:
By glacial acetic acid 60ml, I25.33g (21mmol) joins in the there-necked flask of 250ml, under stirring at room temperature, is slowly dividedly in some parts 3.50g H in 20-30 minute2O2Aqueous solution (mass fraction of 30%), increases the temperature to 35 DEG C under stirring, add 2,4 difluorobenzene formic acid 6.32g (40mmol).Cooling reactant liquor to 10 DEG C, the quickly lower 98%H dripping 53.30ml of stirring2SO4, it is warming up to 50 DEG C after adding and reacts 3 hours, point sample monitoring reaction end.After having reacted, cool down reactant liquor, remove peroxide.Then sucking filtration, washing, obtain 2,4-bis-fluoro-5-iodo-benzoic acid, productivity is 53%.
Embodiment 2: iodine
By glacial acetic acid 300ml, I226.7g (105mmol) joins in the there-necked flask of 1L, under room temperature mechanical stirs, is slowly dividedly in some parts SODIUM PERCARBONATE (SPC) 21.0g (containing 155mmol H in 20-30 minute2O2), increase the temperature to 35 DEG C under stirring, add 2,4 difluorobenzene formic acid 31.6g (200mmol).Cooling reactant liquor to 5 DEG C, the quickly lower 98%H dripping 266.5ml of stirring2SO4, it is warming up to 50 DEG C after adding and reacts 2 hours, point sample monitoring reaction end.After having reacted, cool down reactant liquor, with the Na of 2%2SO3Aqueous solution removes peroxide.Then sucking filtration, washing, obtain 2,4-bis-fluoro-5-iodo-benzoic acid, productivity is 83%.
1-2 in conjunction with the embodiments, and comparative example 1-2, it will thus be seen that
1, the present invention is by the iodide reaction under acid condition, synthesizes 2, and 4-bis-fluoro-5-iodo-benzoic acid, iodine reacts generation I in acid condition with SODIUM PERCARBONATE+Ion.Carrying out electrophilic substitution reaction the most again, eliminate the oxidants such as sodium metaperiodate in conventional method, therefore reaction system compares environmental protection.
2, pass through to seek to affect synthesis 2, the factor of 4-bis-fluoro-5-iodo-benzoic acid productivity, solve the iodide reaction synthesis 2 under acid condition, the yield problem of 4-bis-fluoro-5-iodo-benzoic acid, the synthesis technique of the present invention, reaches as high as 88% (alternative 2), and passes through iodine, productivity still has 83%, is especially suitable for industrialized production.
Claims (7)
1. one kind 2, the preparation method of 4-bis-fluoro-5-iodo-benzoic acid, it is characterised in that: with 2,4 difluorobenzene formic acid as initiation material, iodine and SODIUM PERCARBONATE are iodo reagent, carry out iodide reaction in acid condition, obtain 2,4-bis-fluoro-5-iodo-benzoic acid.
The preparation method of the most according to claim 1 a kind of 2,4-bis-fluoro-5-iodo-benzoic acid, it is characterised in that: described reaction temperature is 45-50 DEG C.
The preparation method of the most according to claim 1 a kind of 2,4-bis-fluoro-5-iodo-benzoic acid, it is characterised in that: the amount of described concentrated sulphuric acid is 48-60 ml.
The preparation method of the most according to claim 1 a kind of 2,4-bis-fluoro-5-iodo-benzoic acid, it is characterised in that: the temperature during dropping of described concentrated sulphuric acid is 0-10 DEG C.
The preparation method of the most according to claim 1 a kind of 2,4-bis-fluoro-5-iodo-benzoic acid, it is characterised in that: described iodine is 1:0.32～1 with the reaction ratio of SODIUM PERCARBONATE.
The preparation method of the most according to claim 1 a kind of 2,4-bis-fluoro-5-iodo-benzoic acid, it is characterised in that: when reaction temperature is 50 DEG C, the usage amount of concentrated sulphuric acid is 53.30ml, when the mol ratio of iodine and SODIUM PERCARBONATE is 1:0.50, the productivity of iodide reaction is the highest, reaches 88%.
The preparation method of the most according to claim 1 a kind of 2,4-bis-fluoro-5-iodo-benzoic acid, it is characterised in that: after having reacted, remove the peroxide of excess with saturated sodium thiosulfate.
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107652175A (en) * | 2017-08-08 | 2018-02-02 | 宁波人健化学制药有限公司 | A kind of synthetic method of the iodo-benzoic acid of 2 methyl 5 |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1956961A (en) * | 2004-05-20 | 2007-05-02 | 日本烟草产业株式会社 | Stable crystal form of 4-oxoquinoline compound |
| WO2011004389A2 (en) * | 2009-06-18 | 2011-01-13 | Matrix Laboratories Ltd | An improved process for the preparation of elvitegravir |
| CN103539662A (en) * | 2013-10-18 | 2014-01-29 | 雅本化学股份有限公司 | Preparation and recovery method of 2-methyl-5-iodobenzoic acid |
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2016
- 2016-05-19 CN CN201610332600.7A patent/CN106008195B/en active Active
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1956961A (en) * | 2004-05-20 | 2007-05-02 | 日本烟草产业株式会社 | Stable crystal form of 4-oxoquinoline compound |
| WO2011004389A2 (en) * | 2009-06-18 | 2011-01-13 | Matrix Laboratories Ltd | An improved process for the preparation of elvitegravir |
| CN103539662A (en) * | 2013-10-18 | 2014-01-29 | 雅本化学股份有限公司 | Preparation and recovery method of 2-methyl-5-iodobenzoic acid |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107652175A (en) * | 2017-08-08 | 2018-02-02 | 宁波人健化学制药有限公司 | A kind of synthetic method of the iodo-benzoic acid of 2 methyl 5 |
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