CN118271351A - Preparation method of 2-hydroxy-4-trifluoromethyl phenylboronic acid - Google Patents
Preparation method of 2-hydroxy-4-trifluoromethyl phenylboronic acid Download PDFInfo
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- GYGNUMOLFBSVCL-UHFFFAOYSA-N [2-hydroxy-4-(trifluoromethyl)phenyl]boronic acid Chemical compound OB(O)C1=CC=C(C(F)(F)F)C=C1O GYGNUMOLFBSVCL-UHFFFAOYSA-N 0.000 title claims abstract description 22
- 238000002360 preparation method Methods 0.000 title claims abstract description 21
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 6
- 150000001875 compounds Chemical class 0.000 claims description 46
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 29
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 24
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 21
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 20
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 16
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 15
- 239000003153 chemical reaction reagent Substances 0.000 claims description 15
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 claims description 14
- 238000006243 chemical reaction Methods 0.000 claims description 14
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 13
- 229910052794 bromium Inorganic materials 0.000 claims description 13
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 12
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 11
- 238000001035 drying Methods 0.000 claims description 10
- 238000000034 method Methods 0.000 claims description 10
- 239000012074 organic phase Substances 0.000 claims description 10
- 239000012071 phase Substances 0.000 claims description 8
- 239000007787 solid Substances 0.000 claims description 8
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 8
- 238000001816 cooling Methods 0.000 claims description 7
- NHDIQVFFNDKAQU-UHFFFAOYSA-N tripropan-2-yl borate Chemical group CC(C)OB(OC(C)C)OC(C)C NHDIQVFFNDKAQU-UHFFFAOYSA-N 0.000 claims description 7
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 6
- 238000005885 boration reaction Methods 0.000 claims description 6
- OSQPUMRCKZAIOZ-UHFFFAOYSA-N carbon dioxide;ethanol Chemical compound CCO.O=C=O OSQPUMRCKZAIOZ-UHFFFAOYSA-N 0.000 claims description 6
- 238000000605 extraction Methods 0.000 claims description 6
- 229910052744 lithium Inorganic materials 0.000 claims description 6
- 229910052757 nitrogen Inorganic materials 0.000 claims description 6
- GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical compound [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 claims description 6
- 238000003756 stirring Methods 0.000 claims description 6
- XJUZRXYOEPSWMB-UHFFFAOYSA-N Chloromethyl methyl ether Chemical compound COCCl XJUZRXYOEPSWMB-UHFFFAOYSA-N 0.000 claims description 5
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 claims description 5
- 239000012295 chemical reaction liquid Substances 0.000 claims description 5
- GQHTUMJGOHRCHB-UHFFFAOYSA-N 2,3,4,6,7,8,9,10-octahydropyrimido[1,2-a]azepine Chemical compound C1CCCCN2CCCN=C21 GQHTUMJGOHRCHB-UHFFFAOYSA-N 0.000 claims description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 4
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 claims description 4
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 4
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 claims description 4
- 239000002253 acid Substances 0.000 claims description 4
- 239000011230 binding agent Substances 0.000 claims description 4
- IUYHWZFSGMZEOG-UHFFFAOYSA-M magnesium;propane;chloride Chemical group [Mg+2].[Cl-].C[CH-]C IUYHWZFSGMZEOG-UHFFFAOYSA-M 0.000 claims description 4
- 238000004519 manufacturing process Methods 0.000 claims description 4
- 239000002904 solvent Substances 0.000 claims description 4
- 238000001914 filtration Methods 0.000 claims description 3
- 239000007788 liquid Substances 0.000 claims description 3
- 238000010791 quenching Methods 0.000 claims description 3
- 230000000171 quenching effect Effects 0.000 claims description 3
- 239000004576 sand Substances 0.000 claims description 3
- 235000010265 sodium sulphite Nutrition 0.000 claims description 3
- 239000000126 substance Substances 0.000 claims description 3
- 238000005406 washing Methods 0.000 claims description 3
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims description 2
- MENYRYNFSIBDQN-UHFFFAOYSA-N 5,5-dibromoimidazolidine-2,4-dione Chemical compound BrC1(Br)NC(=O)NC1=O MENYRYNFSIBDQN-UHFFFAOYSA-N 0.000 claims description 2
- GSNUFIFRDBKVIE-UHFFFAOYSA-N DMF Natural products CC1=CC=C(C)O1 GSNUFIFRDBKVIE-UHFFFAOYSA-N 0.000 claims description 2
- 229960000583 acetic acid Drugs 0.000 claims description 2
- 125000001246 bromo group Chemical group Br* 0.000 claims description 2
- 238000001704 evaporation Methods 0.000 claims description 2
- 239000012362 glacial acetic acid Substances 0.000 claims description 2
- 238000010438 heat treatment Methods 0.000 claims description 2
- 230000001376 precipitating effect Effects 0.000 claims description 2
- JQRYUMGHOUYJFW-UHFFFAOYSA-N pyridine;trihydrobromide Chemical compound [Br-].[Br-].[Br-].C1=CC=[NH+]C=C1.C1=CC=[NH+]C=C1.C1=CC=[NH+]C=C1 JQRYUMGHOUYJFW-UHFFFAOYSA-N 0.000 claims description 2
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims description 2
- WRECIMRULFAWHA-UHFFFAOYSA-N trimethyl borate Chemical compound COB(OC)OC WRECIMRULFAWHA-UHFFFAOYSA-N 0.000 claims description 2
- 239000003795 chemical substances by application Substances 0.000 claims 4
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 claims 2
- 150000002367 halogens Chemical class 0.000 claims 2
- KGBXLFKZBHKPEV-UHFFFAOYSA-N boric acid Chemical compound OB(O)O KGBXLFKZBHKPEV-UHFFFAOYSA-N 0.000 abstract description 3
- 239000004327 boric acid Substances 0.000 abstract description 3
- UGEJOEBBMPOJMT-UHFFFAOYSA-N 3-(trifluoromethyl)phenol Chemical compound OC1=CC=CC(C(F)(F)F)=C1 UGEJOEBBMPOJMT-UHFFFAOYSA-N 0.000 abstract description 2
- 230000002152 alkylating effect Effects 0.000 abstract description 2
- 239000002994 raw material Substances 0.000 abstract description 2
- 239000007858 starting material Substances 0.000 abstract description 2
- 238000003786 synthesis reaction Methods 0.000 abstract description 2
- 230000015572 biosynthetic process Effects 0.000 abstract 1
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 8
- 238000005160 1H NMR spectroscopy Methods 0.000 description 4
- 208000024827 Alzheimer disease Diseases 0.000 description 2
- 201000011240 Frontotemporal dementia Diseases 0.000 description 2
- 208000018737 Parkinson disease Diseases 0.000 description 2
- 239000004698 Polyethylene Substances 0.000 description 2
- 208000024777 Prion disease Diseases 0.000 description 2
- 206010002026 amyotrophic lateral sclerosis Diseases 0.000 description 2
- 230000001276 controlling effect Effects 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 230000004770 neurodegeneration Effects 0.000 description 2
- 102000002639 Eukaryotic Initiation Factor-2B Human genes 0.000 description 1
- 108010082945 Eukaryotic Initiation Factor-2B Proteins 0.000 description 1
- 239000008346 aqueous phase Substances 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- 150000002611 lead compounds Chemical class 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 208000015122 neurodegenerative disease Diseases 0.000 description 1
- 239000002547 new drug Substances 0.000 description 1
- -1 polyethylene Polymers 0.000 description 1
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Abstract
The invention discloses a preparation method of 2-hydroxy-4-trifluoromethyl phenylboronic acid, which belongs to the technical field of pharmaceutical chemistry synthesis and comprises the steps of brominating m-trifluoromethyl phenol serving as a starting material, alkylating, performing metal-halogen exchange to obtain boric acid and the like. Simple operation, mild condition, low equipment requirement, easily available raw materials and high yield, and the total yield of four steps reaches more than 40 percent.
Description
Technical Field
The invention relates to the technical field of pharmaceutical chemical synthesis, in particular to a preparation method of 2-hydroxy-4-trifluoromethyl phenylboronic acid.
Background
2-Hydroxy-4-trifluoromethylphenyl boronic acid is a widely used medical intermediate, and plays an important role in the research of new drugs, and the introduction of boric acid into a lead compound is a common coupling reagent. As described in international patent publication No. WO2019032743A1, 2-hydroxy-4-trifluoromethylphenylboronic acid can be used as an intermediate in the preparation of compounds for the treatment and/or prophylaxis of neurodegenerative diseases, such as neurodegeneration in prion diseases (priondisease). The compounds are useful for treating diseases, disorders or conditions mediated at least in part by Chemicalbook eukaryotic initiation factor 2B, such as Parkinson's Disease (PD), amyotrophic Lateral Sclerosis (ALS), alzheimer's Disease (AD), and frontotemporal dementia (FTD), which have a negative impact on millions of people's lives.
The preparation method of the 2-hydroxy-4-trifluoromethyl phenylboronic acid is not reported.
Disclosure of Invention
Aiming at the problems that the route and the preparation method of the 2-hydroxy-4-trifluoromethyl phenylboronic acid are not recorded in the prior art, the invention provides the preparation method of the 2-hydroxy-4-trifluoromethyl phenylboronic acid, which is prepared by steps of brominating, alkylating, metal-halogen exchanging to obtain boric acid and the like by taking m-trifluoromethyl phenol as a starting material, so as to fill the problems in the background art.
In order to solve the technical problems, the invention adopts the following technical scheme:
A preparation method of 2-hydroxy-4-trifluoromethyl phenylboronic acid comprises the following preparation routes:
preferably, the process for preparing the compounds of formula III is as follows:
Dissolving a compound shown in a formula II in methylene dichloride, adding the methylene dichloride into a four-neck flask, cooling to-20 ℃ by using dry ice ethanol, dropwise adding a solvent for a bromine reagent, controlling the temperature at 0 ℃ after the dropwise adding, reacting for 3 hours, adding a 10% sodium sulfite solution into a reaction solution, stirring for 0.5 hour, standing for separating the solution, washing an organic phase once by using water, drying, preparing sand, and passing a mobile phase EA (PE 1:30) through a column to obtain colorless oily matters shown in the formula III.
Preferably, the compounds of formula IV are prepared as follows:
Adding a compound shown in a formula III, dichloromethane or tetrahydrofuran or methyl tertiary butyl ether into a four-necked flask, cooling to-5 ℃ with ice-salt water, slowly dropwise adding MOMCl, controlling the temperature below 10 ℃ to react for 3 hours after the dropwise adding is finished, adding water into the reaction liquid, stirring for 0.5 hour, standing for separating liquid, drying an organic phase, and evaporating to dryness to obtain a light yellow oily substance, namely the compound shown in the formula IV.
Preferably, the compounds of formula V are prepared as follows:
adding a compound of the formula IV, tetrahydrofuran or diethyl ether and a boration reagent into a four-necked flask, replacing with nitrogen for three times, cooling to-75 to-65 ℃ with dry ice ethanol under the protection of nitrogen, slowly dropwise adding a halogen lithium exchange reagent, slowly recovering the room temperature after the dropwise addition, reacting for 3 hours, dropwise adding water into a reaction solution, quenching the reaction, adding methyl tertiary butyl ether for extraction, adjusting the pH of a water phase to 3-4 with dilute hydrochloric acid, precipitating a white solid, filtering and drying to obtain the white solid, namely the compound of the formula V.
Preferably, the compounds of formula I are prepared as follows:
adding the compound of the formula V, tetrahydrofuran or dioxane into a four-necked flask, adding hydrochloric acid or glacial acetic acid into the four-necked flask at 25 ℃ in water bath, heating to 50 ℃, reacting for 6 hours, adding ethyl acetate into the reaction liquid for extraction, continuously extracting the water phase with ethyl acetate twice, combining the organic phases, drying and concentrating to obtain a white solid, namely the compound of the formula I.
Preferably, the bromine reagent is one of bromine, NBS, dibromohydantoin, liquid bromine or pyridinium tribromide, and the solvent is one of dichloromethane, ethyl acetate or DMF.
Preferably, when the bromine reagent is bromine, the molar ratio of the compound of formula II to bromine is 1:1-1.5.
Preferably, in the reaction of the compounds of the formulae III to IV, the acid-binding agent is selected from one of triethylamine, N, N-diisopropylethylamine or 1, 8-diazabicyclo [5.4.0] undec-7-ene, and when the acid-binding agent is selected from triethylamine, the molar ratio of the compound of the formula III to MOMCl is 1:1-2, and the molar ratio of the compound of the formula III to triethylamine is 1:1-2.
Preferably, the lithium halide exchange reagent is selected from isopropyl magnesium chloride or n-butyl lithium, the boration reagent is selected from triisopropyl borate or trimethyl borate, and when the lithium halide exchange reagent adopts n-butyl lithium and the boration reagent adopts triisopropyl borate, the molar ratio of the compound of formula IV to n-butyl lithium is 1:1.5 to 2, the molar ratio of the compound of the formula IV to the triisopropyl borate is 1:1.5 to 2.
Preferably, the molar ratio of the compound of formula v to hydrochloric acid is 1:2 to 5.
The beneficial effects are that:
The preparation route and the method of the 2-hydroxy-4-trifluoromethyl phenylboronic acid disclosed by the invention are ingenious in design, simple and convenient to operate, mild in condition, low in equipment requirement, easy to obtain raw materials, high in yield, and capable of making up the blank of the prior art, and the total yield of four steps is more than 40%.
Detailed Description
In order to make the objects, technical solutions and advantages of the present invention more apparent, embodiments of the present invention will be described in further detail below.
Example 1: the invention provides a preparation method of 2-hydroxy-4-trifluoromethyl phenylboronic acid, which is prepared by the following route:
Wherein the preparation method of the compound of the formula III comprises the following steps:
Dissolving a compound (16.21 g,0.10mol,1.0 eq) of a formula II in 150ml of dichloromethane, adding the mixture into a 500ml four-necked flask, cooling dry ice ethanol to about minus 20 ℃, dropwise adding 150ml of a dichloromethane solution (15.98 g,0.10mol,1.0 eq) of bromine, reacting for 3 hours at about 0 ℃ after the dropwise addition is finished, adding 200ml of a 10% sodium sulfite solution into the reaction solution, stirring for 0.5 hours, standing for separating liquid, washing an organic phase once with 200ml of water, drying, making sand, and passing a mobile phase EA (polyethylene) 1:30 through a column to obtain 20.6g of colorless oily matter, namely the formula III, wherein the yield is 85.5%.
1HNMR(400MHz，DMSO-d6)δ(ppm):7.06(dd，1H)，7.18(d，1H)，7.72(d，1H)，11.05(s，1H)。
The preparation method of the compound of the formula IV comprises the following steps:
The compound of formula III (20.6 g,0.085mol,1.0 eq), methylene chloride (200 ml), triethylamine (8.60 g,0.085mol,1.0 eq) were added into a 500ml four-necked flask, ice-salt water was cooled to-5 ℃, and then the dropwise addition of MOMCl (6.84 g,0.085mol,1.0 eq) was slowly completed, the reaction was carried out at a temperature of 10 ℃ or lower for 3 hours, water (200 ml) was added into the reaction solution, and after stirring for 0.5 hours, the solution was allowed to stand for separation, the organic phase was dried and evaporated to dryness, whereby 23.0g of a pale yellow oily substance, namely the compound of formula IV, was obtained, with a yield of 95%.
1HNMR(400MHz，DMSO-d6)δ(ppm):7.70(d,1H),7.38(s,1H),7.13-7.19(m,1H),5.29(s,2H),3.37(s,3H)。
Wherein the preparation method of the compound of formula V is as follows:
The compound of formula IV (23.0 g,0.081mol,1.0 eq), tetrahydrofuran (200 ml) and triisopropyl borate (22.76 g,0.121mol,1.5 eq) are added into a 500ml four-mouth flask, nitrogen is replaced for three times, dry ice ethanol is cooled to-75 to-65 ℃ under the protection of nitrogen, n-butyllithium (48.40 ml,0.121mol,1.5 eq) is slowly added dropwise, the reaction is slowly resumed for 3 hours at room temperature, 200ml of water is slowly added into the reaction liquid, the quenching reaction is carried out, 100ml of methyl tertiary butyl ether is added for extraction, the pH of the water phase is regulated to 3-4 by dilute hydrochloric acid, white solid is separated out, and the filtration and drying are carried out, thus obtaining 14.2g of the compound of formula V, and the yield is 70%.
1HNMR(400MHz,DMSO-d6)δ(ppm):7.70(d,1H),7.38(s,1H),7.13-7.19(m,1H),6.02(s,2H),4.20(s,2H)3.30(s,3H).
Wherein the preparation method of the compound of the formula I is as follows:
The compound of formula V (14.2 g,0.057mol,1.0 eq) and 100ml of tetrahydrofuran are added into a 250ml four-necked flask, hydrochloric acid (14.25 ml,0.171mol,3.0 eq) is added into the mixture in a water bath at 25 ℃, the temperature is raised to 50 ℃ for 6 hours, 100ml of ethyl acetate is added into the reaction solution for extraction, 100ml of ethyl acetate is continuously used for extracting 2 from the aqueous phase twice, the organic phases are combined, the organic phases are dried and concentrated, 10.5g of white solid, namely the compound of formula I is obtained, and the yield is 90%.
1HNMR(400MHz，DMSO-d6)δ(ppm):4.33(s,2H)7.06(dd，1H)，7.18(d，1H)，7.72(d，1H)，11.05(s，1H)。
Unless otherwise indicated, the reactant materials of the present invention are all commercially available.
Although the invention has been described hereinabove with reference to embodiments, various modifications thereof may be made and equivalents may be substituted for elements thereof without departing from the scope of the invention. In particular, the features of the disclosed embodiments may be combined with each other in any manner as long as there is no structural conflict, and the exhaustive description of these combinations is not given in this specification merely for the sake of omitting the descriptions and saving resources. Therefore, it is intended that the invention not be limited to the particular embodiment disclosed, but that the invention will include all embodiments falling within the scope of the appended claims.
Claims (10)
1. The preparation method of the 2-hydroxy-4-trifluoromethyl phenylboronic acid is characterized by comprising the following steps of:
2. The process for the preparation of 2-hydroxy-4-trifluoromethylphenylboronic acid according to claim 1, which is characterized in that the process for the preparation of the compound of formula iii is as follows:
Dissolving a compound shown in a formula II in methylene dichloride, adding the methylene dichloride into a four-neck flask, cooling to-20 ℃ by using dry ice ethanol, dropwise adding a solvent for a bromine reagent, controlling the temperature at 0 ℃ after the dropwise adding, reacting for 3 hours, adding a 10% sodium sulfite solution into a reaction solution, stirring for 0.5 hour, standing for separating the solution, washing an organic phase once by using water, drying, preparing sand, and passing a mobile phase EA (PE 1:30) through a column to obtain colorless oily matters shown in the formula III.
3. The process for preparing 2-hydroxy-4-trifluoromethylphenylboronic acid according to claim 2, wherein the compound of formula iv is prepared by the following method:
Adding a compound shown in a formula III, dichloromethane or tetrahydrofuran or methyl tertiary butyl ether into a four-necked flask, cooling to-5 ℃ with ice-salt water, slowly dropwise adding MOMCl, controlling the temperature below 10 ℃ to react for 3 hours after the dropwise adding is finished, adding water into the reaction liquid, stirring for 0.5 hour, standing for separating liquid, drying an organic phase, and evaporating to dryness to obtain a light yellow oily substance, namely the compound shown in the formula IV.
4. A process for the preparation of 2-hydroxy-4-trifluoromethylphenylboronic acid according to claim 3, which comprises the following steps:
adding a compound of the formula IV, tetrahydrofuran or diethyl ether and a boration reagent into a four-necked flask, replacing with nitrogen for three times, cooling to-75 to-65 ℃ with dry ice ethanol under the protection of nitrogen, slowly dropwise adding a halogen lithium exchange reagent, slowly recovering the room temperature after the dropwise addition, reacting for 3 hours, dropwise adding water into a reaction solution, quenching the reaction, adding methyl tertiary butyl ether for extraction, adjusting the pH of a water phase to 3-4 with dilute hydrochloric acid, precipitating a white solid, filtering and drying to obtain the white solid, namely the compound of the formula V.
5. The process for preparing 2-hydroxy-4-trifluoromethylphenylboronic acid according to claim 4, wherein the compound of formula I is prepared by the following method:
adding the compound of the formula V, tetrahydrofuran or dioxane into a four-necked flask, adding hydrochloric acid or glacial acetic acid into the four-necked flask at 25 ℃ in water bath, heating to 50 ℃, reacting for 6 hours, adding ethyl acetate into the reaction liquid for extraction, continuously extracting the water phase with ethyl acetate twice, combining the organic phases, drying and concentrating to obtain a white solid, namely the compound of the formula I.
6. The method for preparing 2-hydroxy-4-trifluoromethyl phenylboronic acid according to claim 2, which is characterized in that the bromine reagent is one of bromine, NBS, dibromohydantoin, liquid bromine or pyridinium tribromide, and the solvent is one of dichloromethane, ethyl acetate or DMF.
7. The method for preparing 2-hydroxy-4-trifluoromethylphenylboronic acid according to claim 6, wherein when the bromine reagent is bromine, the molar ratio of the compound of formula II to bromine is 1:1-1.5.
8. The process for producing 2-hydroxy-4-trifluoromethylphenylboronic acid according to claim 3, wherein the acid-binding agent is one selected from the group consisting of triethylamine, N, N-diisopropylethylamine and 1, 8-diazabicyclo [5.4.0] undec-7-ene in the reaction of the compounds of the formulae III to IV, and the molar ratio of the compound of the formula III to MOMCl is 1:1-2 and the molar ratio of the compound of the formula III to triethylamine is 1:1-2 when the acid-binding agent is selected from the group consisting of triethylamine.
9. The process for preparing 2-hydroxy-4-trifluoromethylphenylboronic acid according to claim 4, wherein the halogen lithium exchanging agent is selected from isopropyl magnesium chloride or n-butyllithium, the boration agent is selected from triisopropyl borate or trimethyl borate, and when n-butyllithium is used as the halogen lithium exchanging agent and triisopropyl borate is used as the boration agent, the molar ratio of the compound of formula IV to n-butyllithium is 1:1.5 to 2, the molar ratio of the compound of the formula IV to the triisopropyl borate is 1:1.5 to 2.
10. The process for the preparation of 2-hydroxy-4-trifluoromethylphenylboronic acid according to claim 5, wherein the molar ratio of the compound of formula v to hydrochloric acid is 1:2 to 5.
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