CN118063495A - Preparation method of 3- (piperidine-1-ylsulfonyl) phenylboronic acid - Google Patents
Preparation method of 3- (piperidine-1-ylsulfonyl) phenylboronic acid Download PDFInfo
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- CN118063495A CN118063495A CN202410186035.2A CN202410186035A CN118063495A CN 118063495 A CN118063495 A CN 118063495A CN 202410186035 A CN202410186035 A CN 202410186035A CN 118063495 A CN118063495 A CN 118063495A
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- ylsulfonyl
- acid
- piperidine
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- phenylboronic acid
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- HQOWPGGTRBFYFE-UHFFFAOYSA-N (3-piperidin-1-ylsulfonylphenyl)boronic acid Chemical compound OB(O)C1=CC=CC(S(=O)(=O)N2CCCCC2)=C1 HQOWPGGTRBFYFE-UHFFFAOYSA-N 0.000 title claims abstract description 19
- 238000002360 preparation method Methods 0.000 title abstract description 9
- 238000006243 chemical reaction Methods 0.000 claims abstract description 31
- HXITXNWTGFUOAU-UHFFFAOYSA-N phenylboronic acid Chemical compound OB(O)C1=CC=CC=C1 HXITXNWTGFUOAU-UHFFFAOYSA-N 0.000 claims abstract description 20
- -1 [3- (chlorosulfonyl) phenyl ] boric acid Chemical compound 0.000 claims abstract description 18
- 238000003756 stirring Methods 0.000 claims abstract description 16
- KEQGZUUPPQEDPF-UHFFFAOYSA-N 1,3-dichloro-5,5-dimethylimidazolidine-2,4-dione Chemical compound CC1(C)N(Cl)C(=O)N(Cl)C1=O KEQGZUUPPQEDPF-UHFFFAOYSA-N 0.000 claims abstract description 11
- XTHPWXDJESJLNJ-UHFFFAOYSA-N chlorosulfonic acid Substances OS(Cl)(=O)=O XTHPWXDJESJLNJ-UHFFFAOYSA-N 0.000 claims abstract description 11
- 239000003960 organic solvent Substances 0.000 claims abstract description 11
- 238000006277 sulfonation reaction Methods 0.000 claims abstract description 5
- 238000005935 nucleophilic addition reaction Methods 0.000 claims abstract description 4
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 20
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical group CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 18
- 239000012074 organic phase Substances 0.000 claims description 18
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 claims description 16
- 238000000034 method Methods 0.000 claims description 14
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 12
- 238000001914 filtration Methods 0.000 claims description 11
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 claims description 9
- 239000002253 acid Substances 0.000 claims description 8
- 239000011230 binding agent Substances 0.000 claims description 8
- 238000001816 cooling Methods 0.000 claims description 8
- JMMWKPVZQRWMSS-UHFFFAOYSA-N isopropanol acetate Natural products CC(C)OC(C)=O JMMWKPVZQRWMSS-UHFFFAOYSA-N 0.000 claims description 7
- 229940011051 isopropyl acetate Drugs 0.000 claims description 7
- GWYFCOCPABKNJV-UHFFFAOYSA-N isovaleric acid Chemical compound CC(C)CC(O)=O GWYFCOCPABKNJV-UHFFFAOYSA-N 0.000 claims description 7
- 239000000243 solution Substances 0.000 claims description 7
- HXJUTPCZVOIRIF-UHFFFAOYSA-N sulfolane Chemical compound O=S1(=O)CCCC1 HXJUTPCZVOIRIF-UHFFFAOYSA-N 0.000 claims description 7
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 6
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 claims description 6
- 239000012065 filter cake Substances 0.000 claims description 6
- 239000000706 filtrate Substances 0.000 claims description 6
- 238000002156 mixing Methods 0.000 claims description 6
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 6
- 238000010438 heat treatment Methods 0.000 claims description 5
- 239000012046 mixed solvent Substances 0.000 claims description 5
- 238000005406 washing Methods 0.000 claims description 5
- KECOYWDLHJMPKO-UHFFFAOYSA-N B(O)(O)OC1=CC(=CC=C1)S(=O)(=O)N2CCCCC2 Chemical compound B(O)(O)OC1=CC(=CC=C1)S(=O)(=O)N2CCCCC2 KECOYWDLHJMPKO-UHFFFAOYSA-N 0.000 claims description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 4
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 claims description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 4
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 claims description 3
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 claims description 3
- HDIWKNXVBQPJCO-UHFFFAOYSA-N ethyl 2-methylsulfanyl-6-oxo-1h-pyrimidine-5-carboxylate Chemical compound CCOC(=O)C1=CN=C(SC)NC1=O HDIWKNXVBQPJCO-UHFFFAOYSA-N 0.000 claims description 3
- 239000005457 ice water Substances 0.000 claims description 3
- 229910052943 magnesium sulfate Inorganic materials 0.000 claims description 3
- 235000019341 magnesium sulphate Nutrition 0.000 claims description 3
- 239000000047 product Substances 0.000 claims description 3
- 238000004537 pulping Methods 0.000 claims description 3
- 239000008346 aqueous phase Substances 0.000 claims description 2
- 239000007864 aqueous solution Substances 0.000 claims description 2
- 238000001035 drying Methods 0.000 claims description 2
- 238000002386 leaching Methods 0.000 claims description 2
- 238000012805 post-processing Methods 0.000 claims description 2
- 238000009776 industrial production Methods 0.000 abstract description 4
- 239000007788 liquid Substances 0.000 description 5
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 4
- RAHZWNYVWXNFOC-UHFFFAOYSA-N Sulphur dioxide Chemical compound O=S=O RAHZWNYVWXNFOC-UHFFFAOYSA-N 0.000 description 4
- 150000001875 compounds Chemical class 0.000 description 4
- 230000004048 modification Effects 0.000 description 4
- 238000012986 modification Methods 0.000 description 4
- 238000005160 1H NMR spectroscopy Methods 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 2
- 230000004071 biological effect Effects 0.000 description 2
- 230000007547 defect Effects 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- IVDFJHOHABJVEH-UHFFFAOYSA-N pinacol Chemical compound CC(C)(O)C(C)(C)O IVDFJHOHABJVEH-UHFFFAOYSA-N 0.000 description 2
- 239000002994 raw material Substances 0.000 description 2
- 125000000565 sulfonamide group Chemical group 0.000 description 2
- NWUYHJFMYQTDRP-UHFFFAOYSA-N 1,2-bis(ethenyl)benzene;1-ethenyl-2-ethylbenzene;styrene Chemical compound C=CC1=CC=CC=C1.CCC1=CC=CC=C1C=C.C=CC1=CC=CC=C1C=C NWUYHJFMYQTDRP-UHFFFAOYSA-N 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 230000000259 anti-tumor effect Effects 0.000 description 1
- KGBXLFKZBHKPEV-UHFFFAOYSA-N boric acid Chemical compound OB(O)O KGBXLFKZBHKPEV-UHFFFAOYSA-N 0.000 description 1
- 239000004327 boric acid Substances 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 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
- 239000003814 drug Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- LBVQLNOQOXKBSE-UHFFFAOYSA-N heptane;propan-2-yl acetate Chemical compound CCCCCCC.CC(C)OC(C)=O LBVQLNOQOXKBSE-UHFFFAOYSA-N 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 239000003456 ion exchange resin Substances 0.000 description 1
- 229920003303 ion-exchange polymer Polymers 0.000 description 1
- 239000000575 pesticide Substances 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 230000000630 rising effect Effects 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 1
- 238000001308 synthesis method Methods 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
Abstract
The invention relates to a preparation method of 3- (piperidine-1-sulfonyl) phenylboronic acid, which comprises the following steps: s1, sulfonation reaction: dissolving phenylboronic acid and chlorosulfonic acid in an organic solvent, stirring for reaction, and performing post-treatment to obtain [3- (chlorosulfonyl) phenyl ] boric acid; s2, nucleophilic addition reaction: the preparation method provided by the invention has the advantages of simple route, simple operation, mild condition, low requirement on equipment, easiness in industrial production and the like.
Description
Technical Field
The invention relates to a preparation method of 3- (piperidine-1-sulfonyl) phenylboronic acid, belonging to the technical field of organic synthesis.
Background
3- (Piperidine-1-base sulfonyl) phenylboronic acid is a compound containing difunctional groups in molecules, wherein the difunctional groups contain sulfonamide groups, the functional groups have special biological activity, and the compound containing sulfonamide groups, which has antitumor activity, is widely studied in medicines or pesticides and is reported at present. The other group boric acid is an important organic building block, and can be introduced into various different compound structures through coupling, so that a series of compounds with broad-spectrum biological activity are generated after modification.
Literature [ Synlett,2004, #5, p.892-894] and WO2004/41833 report that at-100deg.C, N-butyllithium pulls the bromine of 4-bromo N-methyl-diethanolamine phenylboronate, sulfur dioxide is introduced, then NCS is chlorinated to give [3- (chlorosulfonyl) phenyl ] boronic acid, which is finally reacted with piperidine and Dowex50WX2-400 ion exchange resin CAS (12612-37-2) to give 3- (piperidin-1-ylsulfonyl) phenylboronic acid. The total yield is 60.4 percent, but the temperature is ultralow to minus 100 ℃, and the sulfur dioxide is introduced, so that the requirement on equipment is relatively high. The reaction scheme is shown below:
In order to make up for the defects of the existing literature methods, the preparation route of the 3- (piperidine-1-ylsulfonyl) phenylboronic acid needs to be improved, and a synthetic route which is concise in route, simple to operate, mild in condition and more suitable for industrial production is developed.
Disclosure of Invention
The invention aims to overcome the defects of the prior art and provide the synthesis method which has the advantages of high efficiency, mild condition, easily available raw materials, simple process and low requirement on equipment. In the preparation method of the invention, S1, sulfonation reaction: dissolving phenylboronic acid and chlorosulfonic acid in an organic solvent, stirring for reaction, and performing post-treatment to obtain [3- (chlorosulfonyl) phenyl ] boric acid; s2, nucleophilic addition reaction: the preparation method provided by the invention has the advantages of simple route, simple operation, mild condition, low requirement on equipment, easiness in industrial production and the like.
The invention is realized by the following technical scheme: a method for preparing 3- (piperidine-1-ylsulfonyl) phenylboronic acid, comprising the following steps:
S1, sulfonation reaction: mixing phenylboronic acid with the organic solvent I, uniformly stirring, dropwise adding chlorosulfonic acid, then heating until the reaction is complete, and performing post-treatment to obtain [3- (chlorosulfonyl) phenyl ] boric acid;
s2, nucleophilic addition reaction: mixing an acid binding agent, piperidine and an organic solvent II, uniformly stirring, cooling, dropwise adding [3- (chlorosulfonyl) phenyl ] boric acid, then stirring for reacting to completion, and performing post-treatment to obtain the 3- (piperidine-1-ylsulfonyl) phenylboric acid.
The reaction scheme is shown below:
Further, in step S1, the processing is as follows: cooling to room temperature after the reaction is finished, pouring the reaction solution into ice water, standing for layering, reserving an organic phase, extracting an aqueous phase with 1, 2-dichloroethane, combining the organic phases, washing with water, washing with saturated sodium chloride aqueous solution, drying the organic phase with magnesium sulfate, filtering, and concentrating the filtrate under reduced pressure to obtain [3- (chlorosulfonyl) phenyl ] boric acid.
In step S1, the organic solvent I is selected from a mixed solvent of 1, 2-dichloroethane and sulfolane, and the volume ratio of the two is 5-8:1.
Further, in step S1, the reaction temperature is 60-65 ℃.
Further, in the step S1, the molar ratio of the phenylboronic acid to the chlorosulfonic acid is 1:1.3-1.5.
Further, in step S2, the post-processing is: after the reaction is completed, dilute hydrochloric acid is added, standing and layering are carried out, an organic phase is respectively washed by saturated sodium bicarbonate solution and water, the organic phase is concentrated under reduced pressure to replace isopropyl acetate, and finally isopropyl acetate n-heptane is recrystallized to obtain 3- (piperidine-1-ylsulfonyl) phenylboronic acid.
Further, in step S2, the acid-binding agent is selected from Triethylamine (TEA) or N, N-Diisopropylethylamine (DIPEA).
Further, in the step S2, the molar ratio of the [3- (chlorosulfonyl) phenyl ] boric acid to the piperidine to the acid-binding agent is 1:1.1-1.3:1.2-1.3.
Further, in the step S2, the organic solvent II is selected from dichloromethane or 1, 2-dichloroethane, and when the organic phase in the step 1 is concentrated, the step 2 selects dichloromethane as a solvent; when the organic solvent of step 1 is not concentrated, step 2 is performed directly downward, i.e., 1, 2-dichloroethane as a solvent.
Further, the preparation method of the 3- (piperidin-1-ylsulfonyl) phenylboronic acid is also applicable to potassium 3- (piperidin-1-ylsulfonyl) phenyltrifluoroborate. The reaction route is as follows:
Further, the specific steps of the 3- (piperidine-1-ylsulfonyl) phenyl potassium trifluoroborate are as follows: mixing potassium phenyl trifluoroborate with a mixed solvent of 1, 2-dichloroethane and sulfolane, uniformly stirring, dropwise adding chlorosulfonic acid at room temperature, then heating to 65 ℃ for complete reaction, cooling to-20 ℃, adding piperidine, dropwise adding an acid-binding agent, then stirring for complete reaction, filtering, leaching a filter cake with 1, 2-dichloroethane, adding acetone into the filter cake for dissolving a product at room temperature, filtering, concentrating the filtrate, adding MTBE for hot pulping, and filtering to obtain 3- (piperidine-1-ylsulfonyl) potassium phenyl trifluoroborate.
Advantageous effects of the invention
1) By adding the mixed solvent, the raw material solubility is improved, the protonic solvent is increased, and the activity of 3-position phenylboronic acid is higher and the sulfonation speed is higher.
2) The whole route is simple, the operation is simple, the condition is mild, the requirement on equipment is low, and the industrial production is easy to carry out.
Detailed Description
Embodiments of the present invention are described in detail below. For the purpose of illustrating the invention, examples are set forth below. It is to be understood that the invention is not limited to these examples but provides a method of practicing the invention.
Example 1
Phenylboronic acid (24.4 g,0.2 mol), 1, 2-dichloroethane (182 mL) and sulfolane (26 mL) are placed in a reaction bottle at room temperature, chlorosulfonic acid (26.1 g,0.26 mol) is added dropwise, stirred uniformly, placed in an oil bath at 65 ℃ for reaction for 6 hours, cooled to room temperature, the feed liquid is poured into ice water (250 g), 1, 2-dichloroethane (80 mL x 3) is extracted, the organic phases are combined, the organic phases are washed with saturated aqueous sodium chloride solution, the magnesium sulfate is dried, the organic phases are filtered, the filtrate is concentrated under reduced pressure until no liquid is obtained to obtain 35g of [3- (chlorosulfonyl) phenyl ] boronic acid, the yield is 79.4%, and pinacol is derived from GC95.7%. 1 H-NMR (400 MHz, CDCl 3) 8.14 (s, 1H), 8.02-7.96 (m, 2H), 7.35-7.32 (m, 1H), 5.46 (s, 1H).
Example 2
At room temperature, placing [3- (chlorosulfonyl) phenyl ] boric acid (22 g,0.1 mol) and dichloromethane (220 mL) into a jacketed reaction bottle, starting an ice maker and cooling to-20 ℃, firstly dropwise adding piperidine (10.2 g,0.12 mol) into the reaction bottle, dropwise adding triethylamine (13.2 g,0.13 mol), reacting for 2 hours at-20 ℃, adding 3% diluted hydrochloric acid to adjust pH to 1-2, standing for layering, respectively washing an organic phase with saturated sodium bicarbonate solution and water, concentrating the organic phase at 30-35 ℃ under reduced pressure to be a non-flowing liquid, replacing isopropyl acetate (50 mL), and finally recrystallizing isopropyl acetate (35 mL) and n-heptane (125 mL) to obtain 24.2g of 3- (piperidine-1-ylsulfonyl) phenyl boric acid, wherein the yield is 89.8％,HPLC99.7％.1H-NMR(400MHz,DMSO-d6+D2O):8.12(s,1H),8.09(d,1H),7.71(d,1H),7.63(t,1H),2.88-2.82(m,4H),1.62-1.56(m,4H),1.38-1.34(m,2H).
Example 3
Phenylboronic acid (24.4 g,0.2 mol), 1, 2-dichloroethane (182 mL) and sulfolane (26 mL) are placed in a jacketed reaction bottle at room temperature, chlorosulfonic acid (26.1 g,0.26 mol) is added dropwise, after stirring uniformly, the mixture is heated to 65 ℃ for 6 hours in a circulating way, the temperature is reduced to minus 30 ℃, piperidine (22.1 g,0.26 mol) is added dropwise to the reaction bottle, triethylamine (26.3 g,0.26 mol) is added dropwise to the reaction bottle at minus 20 ℃ for 2 hours, 3% diluted hydrochloric acid is added to adjust the pH to 1-2, the mixture is stood and layered, an organic phase is respectively washed with saturated sodium bicarbonate solution and water, the organic phase is concentrated to a non-flowing liquid at 30-35 ℃ under reduced pressure, isopropyl acetate (50 mL) is replaced, isopropyl acetate (60 mL) and n-heptane (240 mL) are recrystallized to obtain 45.3g of 3- (piperidine-1-ylsulfonyl) phenylboronic acid with the yield of 84.2% and HPLC of 98.4%.
Example 4
At room temperature, potassium phenyl trifluoroborate (36.8 g,0.2 mol), 1, 2-dichloroethane (385 mL) and sulfolane (55L) are placed in a jacketed reaction bottle, stirring is started, stirring speed is 500-600rpm, chlorosulfonic acid (30.2 g,0.30 mol) is added dropwise, after stirring is uniform, circulation heating is started until 65 ℃ is carried out for 17 hours, TLC detection reaction is complete, cooling is carried out to-30 ℃, piperidine (25.5 g,0.3 mol) is firstly added dropwise, triethylamine (30.4 g,0.3 mol) is firstly added dropwise, reaction is carried out for 2 hours at-30 to-20 ℃, reaction is carried out for 6 hours at the temperature slowly rising to 10 ℃, TLC detection reaction is complete, filtration is carried out, filter cakes are leached by using 1, 2-dichloroethane, filter cakes are placed in the jacketed reaction bottle again, acetone (300 mL x 2) is added for dissolving products, filtration is carried out, filtrate is concentrated to be a non-flowing liquid at 35-45 ℃ and MTBE (260 mL) is added for hot pulping, and filtration is carried out to obtain 47.6g of 3- (piperidine-1-sulfonyl) potassium benzotrifluoroborate, the yield is obtained 71.9％,HPLC99.2％.1H-NMR(400MHz,DMSO-d6)δ:8.03(s,1H),7.82(d,1H),7.70(d,1H),7.59-7.55(m,1H),2.96-2.90(m,4H),1.55-1.51(m,4H),1.40-1.36(m,2H).
The foregoing is merely a preferred embodiment of the invention, and it is to be understood that the invention is not limited to the form disclosed herein but is not to be construed as excluding other embodiments, but is capable of numerous other combinations, modifications and environments and is capable of modifications within the scope of the inventive concept, either as taught or as a matter of routine skill or knowledge in the relevant art. And that modifications and variations which do not depart from the spirit and scope of the invention are intended to be within the scope of the appended claims.
Claims (10)
1. A method for preparing 3- (piperidine-1-ylsulfonyl) phenylboronic acid, which is characterized by comprising the following steps:
S1, sulfonation reaction: mixing phenylboronic acid with the organic solvent I, uniformly stirring, dropwise adding chlorosulfonic acid, then heating until the reaction is complete, and performing post-treatment to obtain [3- (chlorosulfonyl) phenyl ] boric acid;
s2, nucleophilic addition reaction: mixing an acid binding agent, piperidine and an organic solvent II, uniformly stirring, cooling, dropwise adding [3- (chlorosulfonyl) phenyl ] boric acid, then stirring for reacting to completion, and performing post-treatment to obtain the 3- (piperidine-1-ylsulfonyl) phenylboric acid.
2. The method for preparing 3- (piperidin-1-ylsulfonyl) phenylboronic acid according to claim 1, which is characterized in that: in step S1, the organic solvent I is selected from a mixed solvent of 1, 2-dichloroethane and sulfolane.
3. The method for preparing 3- (piperidin-1-ylsulfonyl) phenylboronic acid according to claim 1, which is characterized in that: in step S1, the reaction temperature is 60-65 ℃.
4. The method for preparing 3- (piperidin-1-ylsulfonyl) phenylboronic acid according to claim 1, which is characterized in that: in the step S1, the molar ratio of the phenylboronic acid to the chlorosulfonic acid is 1:1.3-1.5.
5. The method for preparing 3- (piperidin-1-ylsulfonyl) phenylboronic acid according to claim 1, which is characterized in that: in step S1, the post-processing is: cooling to room temperature after the reaction is finished, pouring the reaction solution into ice water, standing for layering, reserving an organic phase, extracting an aqueous phase with 1, 2-dichloroethane, combining the organic phases, washing with water, washing with saturated sodium chloride aqueous solution, drying the organic phase with magnesium sulfate, filtering, and concentrating the filtrate under reduced pressure to obtain [3- (chlorosulfonyl) phenyl ] boric acid.
6. The method for preparing 3- (piperidin-1-ylsulfonyl) phenylboronic acid according to claim 1, which is characterized in that: in step S2, the acid binding agent is selected from triethylamine or diisopropylethylamine.
7. The method for preparing 3- (piperidin-1-ylsulfonyl) phenylboronic acid according to claim 1, which is characterized in that: in step S2, the organic solvent II is selected from dichloromethane or 1, 2-dichloroethane.
8. The method for preparing 3- (piperidin-1-ylsulfonyl) phenylboronic acid according to claim 1, which is characterized in that: in the step S2, the molar ratio of the [3- (chlorosulfonyl) phenyl ] boric acid, the piperidine and the acid-binding agent is 1:1.1-1.3:1.2-1.3.
9. The method for preparing 3- (piperidin-1-ylsulfonyl) phenylboronic acid according to claim 1, which is characterized in that: in the step S2, the post-treatment is that dilute hydrochloric acid is added, standing and layering are carried out, saturated sodium bicarbonate solution and water are respectively used for the organic phase, the organic phase is concentrated under reduced pressure to replace isopropyl acetate, and finally isopropyl acetate and n-heptane are recrystallized to obtain 3- (piperidine-1-ylsulfonyl) phenylboric acid.
10. A method for preparing 3- (piperidine-1-ylsulfonyl) phenyl potassium trifluoroborate, which is characterized by comprising the following steps:
Mixing potassium phenyl trifluoroborate with a mixed solvent of 1, 2-dichloroethane and sulfolane, uniformly stirring, dropwise adding chlorosulfonic acid at room temperature, then heating to 65 ℃ for complete reaction, cooling to-20 ℃, adding piperidine, dropwise adding an acid-binding agent, then stirring for complete reaction, filtering, leaching a filter cake with 1, 2-dichloroethane, adding acetone into the filter cake for dissolving a product at room temperature, filtering, concentrating the filtrate, adding MTBE for hot pulping, and filtering to obtain 3- (piperidine-1-ylsulfonyl) potassium phenyl trifluoroborate.
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