CN105541887B - A kind of method for preparing the aldehyde radical phenyl boric acid of 3 fluorine 2 - Google Patents
A kind of method for preparing the aldehyde radical phenyl boric acid of 3 fluorine 2 Download PDFInfo
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- 238000000034 method Methods 0.000 title claims abstract description 19
- HXITXNWTGFUOAU-UHFFFAOYSA-N phenylboronic acid Chemical compound OB(O)C1=CC=CC=C1 HXITXNWTGFUOAU-UHFFFAOYSA-N 0.000 title claims abstract description 12
- 125000002485 formyl group Chemical class [H]C(*)=O 0.000 title claims abstract description 5
- YCKRFDGAMUMZLT-UHFFFAOYSA-N Fluorine atom Chemical compound [F] YCKRFDGAMUMZLT-UHFFFAOYSA-N 0.000 title abstract 3
- 229910052731 fluorine Inorganic materials 0.000 title abstract 3
- 239000011737 fluorine Substances 0.000 title abstract 3
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 claims abstract description 15
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims abstract description 15
- 239000003153 chemical reaction reagent Substances 0.000 claims abstract description 15
- 239000012043 crude product Substances 0.000 claims abstract description 12
- 238000010992 reflux Methods 0.000 claims abstract description 9
- 239000002253 acid Substances 0.000 claims abstract description 8
- 125000005619 boric acid group Chemical class 0.000 claims abstract description 8
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 claims abstract description 7
- 229910052744 lithium Inorganic materials 0.000 claims abstract description 7
- DWAQJAXMDSEUJJ-UHFFFAOYSA-M Sodium bisulfite Chemical compound [Na+].OS([O-])=O DWAQJAXMDSEUJJ-UHFFFAOYSA-M 0.000 claims abstract description 5
- 229940079827 sodium hydrogen sulfite Drugs 0.000 claims abstract description 5
- 235000010267 sodium hydrogen sulphite Nutrition 0.000 claims abstract description 5
- 230000018044 dehydration Effects 0.000 claims abstract description 4
- 238000006297 dehydration reaction Methods 0.000 claims abstract description 4
- 230000005595 deprotonation Effects 0.000 claims abstract description 4
- 238000010537 deprotonation reaction Methods 0.000 claims abstract description 4
- 238000006243 chemical reaction Methods 0.000 claims description 20
- OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 claims description 10
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 10
- 230000007062 hydrolysis Effects 0.000 claims description 4
- 238000006460 hydrolysis reaction Methods 0.000 claims description 4
- QAOWNCQODCNURD-UHFFFAOYSA-N sulfuric acid group Chemical class S(O)(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 4
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical group CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 3
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 claims description 3
- WBJINCZRORDGAQ-UHFFFAOYSA-N formic acid ethyl ester Natural products CCOC=O WBJINCZRORDGAQ-UHFFFAOYSA-N 0.000 claims description 3
- 230000005311 nuclear magnetism Effects 0.000 claims description 3
- 238000012545 processing Methods 0.000 claims description 2
- 238000004451 qualitative analysis Methods 0.000 claims description 2
- FEWLNYSYJNLUOO-UHFFFAOYSA-N 1-Piperidinecarboxaldehyde Chemical compound O=CN1CCCCC1 FEWLNYSYJNLUOO-UHFFFAOYSA-N 0.000 claims 1
- 239000011903 deuterated solvents Substances 0.000 claims 1
- 235000010338 boric acid Nutrition 0.000 abstract description 12
- 239000000543 intermediate Substances 0.000 abstract 1
- 238000004519 manufacturing process Methods 0.000 abstract 1
- 238000000926 separation method Methods 0.000 abstract 1
- 239000000243 solution Substances 0.000 description 14
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 12
- 230000015572 biosynthetic process Effects 0.000 description 8
- 239000000047 product Substances 0.000 description 8
- 238000003786 synthesis reaction Methods 0.000 description 8
- KGBXLFKZBHKPEV-UHFFFAOYSA-N boric acid Chemical compound OB(O)O KGBXLFKZBHKPEV-UHFFFAOYSA-N 0.000 description 6
- 239000004327 boric acid Substances 0.000 description 6
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 6
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 4
- 238000000605 extraction Methods 0.000 description 4
- 239000012044 organic layer Substances 0.000 description 4
- 239000007787 solid Substances 0.000 description 4
- 238000003756 stirring Methods 0.000 description 4
- 238000005406 washing Methods 0.000 description 4
- 238000004128 high performance liquid chromatography Methods 0.000 description 3
- ZOXJGFHDIHLPTG-UHFFFAOYSA-N Boron Chemical compound [B] ZOXJGFHDIHLPTG-UHFFFAOYSA-N 0.000 description 2
- 102000004190 Enzymes Human genes 0.000 description 2
- 108090000790 Enzymes Proteins 0.000 description 2
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 2
- 206010028980 Neoplasm Diseases 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 229910052796 boron Inorganic materials 0.000 description 2
- QARVLSVVCXYDNA-UHFFFAOYSA-N bromobenzene Chemical compound BrC1=CC=CC=C1 QARVLSVVCXYDNA-UHFFFAOYSA-N 0.000 description 2
- 201000011510 cancer Diseases 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 238000004821 distillation Methods 0.000 description 2
- 229910052736 halogen Inorganic materials 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- 125000000623 heterocyclic group Chemical group 0.000 description 2
- 239000010410 layer Substances 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 238000012423 maintenance Methods 0.000 description 2
- 238000005360 mashing Methods 0.000 description 2
- 229910052757 nitrogen Inorganic materials 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 238000011084 recovery Methods 0.000 description 2
- 239000012047 saturated solution Substances 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- PYOKUURKVVELLB-UHFFFAOYSA-N trimethyl orthoformate Chemical compound COC(OC)OC PYOKUURKVVELLB-UHFFFAOYSA-N 0.000 description 2
- JWUJQDFVADABEY-UHFFFAOYSA-N 2-methyltetrahydrofuran Chemical class CC1CCCO1 JWUJQDFVADABEY-UHFFFAOYSA-N 0.000 description 1
- RODIZIAGKGVKKT-UHFFFAOYSA-N C1=CC=C2C3=C4C=NNC4=CC=C3N=CC2=C1 Chemical class C1=CC=C2C3=C4C=NNC4=CC=C3N=CC2=C1 RODIZIAGKGVKKT-UHFFFAOYSA-N 0.000 description 1
- YZCKVEUIGOORGS-OUBTZVSYSA-N Deuterium Chemical compound [2H] YZCKVEUIGOORGS-OUBTZVSYSA-N 0.000 description 1
- LXDRHVXMGDKBEK-UHFFFAOYSA-N [B].C1=CC=CC=C1 Chemical compound [B].C1=CC=CC=C1 LXDRHVXMGDKBEK-UHFFFAOYSA-N 0.000 description 1
- KYOIPUDHYRWSFO-UHFFFAOYSA-N [Br].[Li] Chemical compound [Br].[Li] KYOIPUDHYRWSFO-UHFFFAOYSA-N 0.000 description 1
- DHKHKXVYLBGOIT-UHFFFAOYSA-N acetaldehyde Diethyl Acetal Natural products CCOC(C)OCC DHKHKXVYLBGOIT-UHFFFAOYSA-N 0.000 description 1
- 125000002777 acetyl group Chemical class [H]C([H])([H])C(*)=O 0.000 description 1
- 238000005903 acid hydrolysis reaction Methods 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 238000007259 addition reaction Methods 0.000 description 1
- 230000003321 amplification Effects 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 238000012790 confirmation Methods 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 229910052805 deuterium Inorganic materials 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 239000002532 enzyme inhibitor Substances 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 239000012847 fine chemical Substances 0.000 description 1
- 206010020718 hyperplasia Diseases 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- -1 layering Substances 0.000 description 1
- 239000000178 monomer Substances 0.000 description 1
- 238000003199 nucleic acid amplification method Methods 0.000 description 1
- 150000003053 piperidines Chemical class 0.000 description 1
- 238000004886 process control Methods 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 235000002639 sodium chloride Nutrition 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F5/00—Compounds containing elements of Groups 3 or 13 of the Periodic Table
- C07F5/02—Boron compounds
- C07F5/025—Boronic and borinic acid compounds
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Compositions Of Macromolecular Compounds (AREA)
Abstract
The invention discloses a kind of method for preparing the aldehyde radical phenyl boric acid of 3 fluorine 2.From 3 fluorobenzoic boric acids, tripolymer is formed after dehydration is heated to reflux in toluene or heptane, the subsequent tripolymer adds lithium reagent deprotonation, is subsequently added aldehyde radical reagent, after acid is quenched, crude product obtains the aldehyde radical phenyl boric acid sterling of 3 fluorine 2 after being handled using sodium hydrogensulfite.This method is easy to operate, it is to avoid common process need aldehyde radical protect after separation of intermediates process, without ultralow temperature, purifying is convenient, is adapted to scale volume production.
Description
Technical field
The present invention relates to a kind of method for preparing the fluoro- 2- aldehyde radicals phenyl boric acids of 3-, belong to fine-chemical intermediate synthesis field.
Background technology
In recent years, the incidence of disease of cancer is higher, and Pim enzymes are considered as to play important tune in cancer cell hyperplasia and surviving path
Control is acted on, and is studied the Pim enzyme inhibitors of new type heterocycle skeleton and is just turned into new study hotspot.It is used as new type heterocycle Pim enzyme levels
The important feature unit of agent (Pyrazolo [4,3-a] phenanthridines, structure is as follows), the fluoro- 2- aldehyde radicals phenyl boric acids of 3-
It is exactly crucial intermediate feed.
At present, the synthetic method of the fluoro- 2- aldehyde radicals phenyl boric acids of 3- is there is not yet open source information is reported, according to document（With reference to：New. J. Chem. 2007,31, 144) and analogy, it can be found that 3- halogen -2- aldehyde radicals phenyl boric acid is synthesized：From the aldehyde radical bromobenzene of 3- halogen -2,
Acetal is first protected into trimethyl orthoformate, is then occurred with butyl lithium condition of ultralow temperature after bromine lithium exchanges, then with boron triethylenetetraminehexaacetic acid
Low temperature acid hydrolysis obtains target product after ester reaction.Need to be protected in aldehyde radical in this method synthesis, simultaneous reactions are also needed
Want to carry out under ultralow temperature, when being amplified synthesis in the method, product impurity is more, purification difficult.
The content of the invention
In order to overcome drawbacks described above, the present invention is set out using using 3- fluorobenzoic boric acids, and tripolymer is formed by dehydration, is utilized
The characteristics of tripolymer is stablized in the basic conditions, adds after the selective deprotonation of LDA or TEMPLi, and aldehyde radical reagent reacting,
Boric acid tripolymer is hydrolyzed into boric acid while acid is quenched, and crude product obtains the fluoro- 2- aldehyde radicals benzene boron of 3- after being handled using sodium hydrogensulfite
Sour sterling.
A kind of method for preparing the fluoro- 2- aldehyde radicals phenyl boric acids of 3-, it is characterised in that comprise the following steps：
The first step：3- fluorobenzoic boric acids form tripolymer after dehydration is heated to reflux in toluene or heptane；
Second step：Above-mentioned tripolymer adds lithium reagent deprotonation, is subsequently added aldehyde radical reagent, reaction terminates, reaction solution
It is added dropwise in acid and is quenched, while obtains the fluoro- 2- aldehyde radicals phenyl boric acid crude products of 3- after tripolymer hydrolysis；
3rd step：Above-mentioned crude product obtains the fluoro- 2- aldehyde radicals phenyl boric acid sterlings of 3- after adding sodium hydrogensulfite processing.
Further, in the above-mentioned technical solutions, in second step, lithium reagent is selected from LDA or TEMPLi.
Further, in the above-mentioned technical solutions, in second step, aldehyde radical reagent is selected from DMF, Ethyl formate or formoxyl
Piperidines.
Further, in the above-mentioned technical solutions, in second step, tripolymer, lithium reagent and aldehyde radical reagent mol ratio are
1:3-3.6:3-5。
Further, in the above-mentioned technical solutions, in second step, it is quenched under acid condition, selected from 5-15% aqueous hydrochloric acid solutions
Or 3-8% aqueous sulfuric acids adjust PH to be 1-2.
Further, in the above-mentioned technical solutions, in the 3rd step, the qualitative analysis of product nuclear-magnetism need to be using CD3OD as deuterium
For solvent.
Invention beneficial effect
Route of the present invention is novel, compared with conventional method, is protected this method avoid prior aldehyde radical is needed in previous methods
Operation, synthesis step is short, easy to operate, is conducive to amplification to produce.
Mode is quenched in the difference of reaction influences very big to reaction yield, and reaction solution is added dropwise in acid by the present invention so that quenched
Acidic aqueous solution environment is constantly in during going out, it is to avoid in sour addition reaction solution mode, system from alkaline environment excessively to
Sour environment, reduces boron removal product.
The characteristics of purifying of product utilizes aldehyde radical itself, adds sodium hydrogensulfite into salt, the mode then dissociated again, purifying
Product HPLC purity can reach more than 99.5% afterwards.
Due to itself there is the situation that self condenses in product, nmr analysis are structure-characterized always to be difficult point, and the present invention is used
CD3OD makees nuclear-magnetism solvent so that monomer and self shrinking conjunction state can all be transformed into singlet state, so that counter push away confirmation product knot
Structure.
Embodiment
Embodiment 1
The synthesis of 3- fluorobenzoic boric acid tripolymers：
In the 1L there-necked flask equipped with reflux water-dividing device, 3- fluorobenzoic boric acids (140 grams, 1.0 moles) and 650 are added
Milliliter normal heptane, is heated to reflux water-dividing, when system separates about 18.3 grams of water, and system there is no water when continuing to separate, and stops
Only react.After cooling, heptane is distilled to not flow liquid, 3- fluorobenzoic boric acid tripolymers are obtained, now containing about 5% heptane.
The synthesis of the fluoro- 2- aldehyde radicals phenyl boric acid crude products of 3-：
Under nitrogen protection, 3- fluorobenzoic boric acids tripolymer obtained above is added into 600 milliliters of dissolvings of anhydrous tetrahydro furan equal
After even, it is transferred in there-necked flask, system is then cooled to -10 DEG C to -20 DEG C, adds 1M LDA (1.0 liters, 1.0 moles).
After insulated and stirred 30 minutes, start to be slowly added dropwise in DMF (88 grams, 1.2 moles), adition process control temperature not more than-
10 DEG C, addition finishes maintenance and continues stirring reaction at this temperature 1-3 hours, and stirring 3-5 hours is then warmed to room temperature naturally.TLC
System after completion of the reaction, is cooled to 0 DEG C by detection, and reaction solution is added dropwise into 15% aqueous hydrochloric acid solution is quenched reaction, and addition finishes survey
PH=1-2, continues to be stirred at room temperature 2-3 hours, it is ensured that tripolymer hydrolysis is complete.Add 600 milliliters of extractions of ethyl acetate, layering, water
Layer is discarded.Organic layer obtains the fluoro- 2- aldehyde radicals phenyl boric acid crude products of yellow solid 3- after being spin-dried for.
The purifying of the fluoro- 2- aldehyde radicals phenyl boric acids of 3-：
Above-mentioned dissolving crude product adds NaHSO in 320 milliliters of tetrahydrofurans3Saturated solution, heating reflux reaction cooled
Filter solid, adds 10% aqueous hydrochloric acid solution and adjusts PH=2-3,550 milliliters of extractions of ethyl acetate, washing, saturated common salt washing, distillation
Organic layer, normal heptane mashing, is filtrated to get 123 grams of the fluoro- 2- aldehyde radicals phenyl boric acids of off-white powder 3-, HPLC：99.6%, total recovery
73%, HNMR (400MHz, CD3OD): 7.39(m, 2H), 7.15(m, 1H), 6.14(s, 1H).
Embodiment 2
The synthesis of 3- fluorobenzoic boric acid tripolymers：
In the 1L there-necked flask equipped with reflux water-dividing device, 3- fluorobenzoic boric acids (140 grams, 1.0 moles) and 550 are added
Milliliter toluene, is heated to reflux water-dividing, when system separates about 18.5 grams of water, and system there is no water when continuing to separate, and stops
Reaction.After cooling, heptane is distilled to not flow liquid, 3- fluorobenzoic boric acid tripolymers are obtained, now containing about 4% toluene.
The synthesis of the fluoro- 2- aldehyde radicals phenyl boric acid crude products of 3-：
Under nitrogen protection, 3- fluorobenzoic boric acids tripolymer obtained above is added into the 500 milliliters of dissolvings of 2- methyltetrahydrofurans
After uniform, it is transferred in there-necked flask, system is then cooled to -10 DEG C to -20 DEG C, adds 1M TEMPLi (1.1 liters, 1.1
Mole).After insulated and stirred 30 minutes, start to be slowly added dropwise in Ethyl formate (89 grams, 1.2 moles), adition process and control temperature
Not more than -10 DEG C, addition finishes maintenance and continues stirring reaction at this temperature 1-3 hours, is then warmed to room temperature stirring naturally
3-5 hours.TLC is detected after completion of the reaction, system is cooled into 0 DEG C, reaction solution is added dropwise into 5% aqueous sulfuric acid is quenched reaction,
Addition finishes survey PH=1, continues to be stirred at room temperature 2-3 hours, it is ensured that tripolymer hydrolysis is complete.Add 650 milliliters of extractions of ethyl acetate
Take, be layered, water layer discarded.Organic layer obtains the fluoro- 2- aldehyde radicals phenyl boric acid crude products of yellow solid 3- after being spin-dried for.
The purifying of the fluoro- 2- aldehyde radicals phenyl boric acids of 3-：
Above-mentioned dissolving crude product adds NaHSO in 300 milliliters of tetrahydrofurans3Saturated solution, heating reflux reaction cooled
Filter solid, adds 15% aqueous hydrochloric acid solution and adjusts PH=2-3,580 milliliters of extractions of ethyl acetate, washing, saturated common salt washing, distillation
Organic layer, normal heptane mashing, is filtrated to get 119 grams of the fluoro- 2- aldehyde radicals phenyl boric acids of off-white powder 3-, HPLC：99.8%, total recovery
71%, HNMR (400MHz, CD3OD): 7.39(m, 2H), 7.15(m, 1H), 6.14(s, 1H).
Claims (6)
1. a kind of method for preparing the fluoro- 2- aldehyde radicals phenyl boric acids of 3-, it is characterised in that comprise the following steps：
The first step：3- fluorobenzoic boric acids form tripolymer after dehydration is heated to reflux in toluene or heptane；
Second step：Above-mentioned tripolymer adds lithium reagent deprotonation, is subsequently added aldehyde radical reagent, after reaction terminates, reaction solution adds
Enter in acid and be quenched, while obtaining the fluoro- 2- aldehyde radicals phenyl boric acid crude products of 3- after tripolymer hydrolysis；
3rd step：Above-mentioned crude product obtains the fluoro- 2- aldehyde radicals phenyl boric acid sterlings of 3- after adding sodium hydrogensulfite processing.
2. a kind of method for preparing the fluoro- 2- aldehyde radicals phenyl boric acids of 3- according to claim 1, it is characterised in that：In second step, lithium
Reagent is selected from LDA or TEMPLi.
3. a kind of method for preparing the fluoro- 2- aldehyde radicals phenyl boric acids of 3- according to claim 1, it is characterised in that：In second step, aldehyde
Base reagent is selected from DMF, Ethyl formate or formyl piperidine.
4. a kind of method for preparing the fluoro- 2- aldehyde radicals phenyl boric acids of 3- according to claim 1, it is characterised in that：In second step, three
Aggressiveness, lithium reagent and aldehyde radical reagent mol ratio are 1:3-3.6:3-5.
5. a kind of method for preparing the fluoro- 2- aldehyde radicals phenyl boric acids of 3- according to claim 1, it is characterised in that：In second step, acid
Property under the conditions of be quenched, adjust pH to be 1-2 selected from 5-15% aqueous hydrochloric acid solutions or 3-8% aqueous sulfuric acids.
6. a kind of method for preparing the fluoro- 2- aldehyde radicals phenyl boric acids of 3- according to claim 1, it is characterised in that：Produced in 3rd step
The qualitative analysis of thing nuclear-magnetism need to be using CD3OD as deuterated solvent.
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| DE10032017A1 (en) * | 2000-07-01 | 2002-01-10 | Clariant Gmbh | Process for the production of high-purity formylphenylboronic acids |
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