CN106278847A - Compound, its preparation method and application containing a fluoroalkyl - Google Patents

Compound, its preparation method and application containing a fluoroalkyl Download PDF

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CN106278847A
CN106278847A CN201510268169.XA CN201510268169A CN106278847A CN 106278847 A CN106278847 A CN 106278847A CN 201510268169 A CN201510268169 A CN 201510268169A CN 106278847 A CN106278847 A CN 106278847A
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substituted
unsubstituted
compound
hetero atom
fluoroalkyl
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CN106278847B (en
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张新刚
安伦
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Shanghai Institute of Organic Chemistry of CAS
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Shanghai Institute of Organic Chemistry of CAS
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C17/00—Preparation of halogenated hydrocarbons
    • C07C17/26—Preparation of halogenated hydrocarbons by reactions involving an increase in the number of carbon atoms in the skeleton

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Abstract

The invention discloses compound containing a fluoroalkyl and preparation method thereof.The invention provides the preparation method of a kind of compound containing a fluoroalkyl, comprise the following steps: in a solvent, under conditions of alkali, additive, part and catalyst exist, compound A and compound B is carried out suzuki coupling reaction, obtain compound C, catalyst is nickel salt, and described nickel salt is NiLnCl2、NiLnBr2、NiLnI2Or NiQ2·mH2O.The preparation method of the present invention by single step reaction just can introduce a fluoroalkyl, high-efficient simple, functional group compatibility is good, broad spectrum activity is strong, can avoid use poisonous reagent, post-processing operation is simple and safe, environmental friendliness, catalyst are cheap and consumption is low, reaction condition is gentle, reaction conversion ratio is high, yield is high, production cost is low, be suitable for industrialized production.

Description

Compound, its preparation method and application containing a fluoroalkyl
Technical field
The present invention relates to the compound containing a fluoroalkyl, its preparation method and application.
Background technology
The substituted aromatic compound of fluoroalkyl suffers from important application at medicine, pesticide and material science.Although Recent years introduces some report of fluoroalkyl to aromatic ring, but the synthetic method of the compound containing a fluoroalkyl is reported Less.
Due to the unique reason of fluorine atom, change, biological property, this kind of compound of a fluoroalkyl that contains is at life science Have very important application ((a) B.E.Smart, J.Fluorine Chem.2001,109,3；(b) P.Maienfisch, R.G.Hall, Chimia.2004,58,93；(c) Special issue on " Fluorine in the Life Sciences ", ChemBioChem.2004,5,557；(d) F.Babudri, G.M.Farinola, F.Naso, R.Ragni, Chem. Commun.2007,1003；(e) K.M ü ller, C.Faeh, F.Diederich, Science 2007,317,1881；(f) S.Purser, P.R.Moore, S.Swallow, V.Gouverneur, Chem.Soc.Rev.2008,37,320.).Mesh The transition metal of front application equivalent or catalytic amount synthesizes the method for this compounds and also only has a small amount of several examples ((a) H. Doi, I.Ban, A.Nonoyama, K.Sumi, C.Kuang, T.Hosoya, H.Tsukada, M.Suzuki, Chem. Eur.J.2009,15,4165；(b) H.Doi, M.Goto, M.Suzuki, Bull.Chem.Soc.Jpn.2012,11, 1233；(c) Y.Zhao, B.Gao, C.Ni, J.Hu, Org.Lett.2012,14,6080；(d) Y.Zhao, C.Ni, F. Jiang, B.Gao, X.Shen, J.Hu, ACS Catal.2013,3,631.) and these methods yet suffer from some shortcomings, Severe reaction conditions, expensive catalyst, functional group compatibility is bad, and broad spectrum activity is bad.Such as, list of references b It is aryl-boric acid ester based on palladium chtalyst and fluorine bromomethane or the cross-coupling reaction of fluorine iodomethane, but this reaction needs Using the aryl-boric acid ester of 40 times of equivalents, applicable substrate spectrum is limited, and reaction efficiency has much room for improvement.Therefore, visit Rope one high-efficient simple, functional group compatibility are good, catalyst is cheap and consumption is low, reaction condition is gentle, reactions steps Short, reaction conversion ratio is high, yield is high, the preparation method containing the compound of a fluoroalkyl that is suitable for industrialized production is It is badly in need of at present solving the technical problem that.
Summary of the invention
The technical problem to be solved is the preparation side in order to overcome the compound containing a fluoroalkyl in prior art Method reactions steps is loaded down with trivial details, functional group compatibility is poor, catalyst is expensive, consumption is high, severe reaction conditions, reaction Step length, reaction conversion ratio are low, yield is low, be not suitable for the defects such as industrialized production and provide a kind of containing a halothane The compound of base, its preparation method and application.The preparation method of the present invention by single step reaction just can introduce a fluoroalkyl, High-efficient simple, functional group compatibility are good, broad spectrum activity is strong, can avoid using poisonous reagent, post-processing operation simple and safe, Environmental friendliness, catalyst are cheap and consumption is low, reaction condition is gentle, reaction conversion ratio is high, yield is high, production cost Low, be suitable for industrialized production.The compound containing a fluoroalkyl that the present invention prepares preparation medicine, pesticide or Being widely used in medical material, the marketization has good prospects.
The invention provides the preparation method of a kind of compound containing a fluoroalkyl, it comprises the following steps: in a solvent, Under conditions of alkali, additive, part and catalyst exist, compound A and compound B is carried out suzuki coupling Reaction, obtains compound C, and described catalyst is nickel salt, and described nickel salt is NiLnCl2(such as NiCl2·DME、NiCl2(PPh3)2Or NiCl2·dppe)、NiLnBr2、NiLnI2Or NiQ2·mH2O (such as NiCl2、 NiBr2、NiI2、NiCl2·6H2O、NiBr2·3H2O、Ni(OAc)2、Ni(acac)2, or Ni (NO3)2·6H2O)；
Wherein, Q is nitrate anion, acetate, acetylacetone,2,4-pentanedione root, chlorine, bromine or iodine, and 0≤m≤10 (such as 0,1,2, 3,4,5,6,7,8,9 or 10)；And 0≤n ＜ 3 (such as 0,1,2 or 3)；L is triphenylphosphine, O-methoxy three Phenylphosphine, adjacent methyl triphenyl phosphine, tri-butyl phosphine, tricyclohexyl phosphine, three adamantyl phosphines, 1,2 pairs (diphenylphosphine) Ethane (dppe), 1,3-double (diphenylphosphine) propane (dppp), Isosorbide-5-Nitrae-bis-(diphenylphosphine) butane (dppb), 1,1 '-bis-(hexichol Base phosphine) ferrocene (dppf), double diphenylphosphine methane (dppm), 1,2-double two triphenylphosphine benzene (dppbz), dimethyl second Diether (DME), diethylene glycol dimethyl ether (Diglyme), " substituted or unsubstituted 1,10-phenanthrene quinoline " are (described " not Substituted 1,10-phenanthrene quinoline " preferablyDescribed " substituted 1,10-phenanthrene quinoline " is preferred), " substituted or unsubstituted pyridine " (described " substituted pyridine " is preferred), (described " substituted bipyridyl " is preferred for substituted or unsubstituted bipyridyl
) or(such as ), described " substituted or unsubstituted bipyridyl ", " replacement or unsubstituted 1,10-phenanthrene quinoline " or " replace or substituted pyridine " described in " replacement " refer in heteroatomic non-ortho by C1~ C10Alkyl (preferably C1～C6Alkyl, described " C1～C6Alkyl " such as methyl, ethyl, propyl group, different Propyl group, butyl, isobutyl group or the tert-butyl group), C1～C10Alkoxyl (preferably C1～C6Alkoxyl, described “C1～C6Alkoxyl " such as methoxyl group, ethyoxyl, propoxyl group, isopropoxy, butoxy, isobutoxy or uncle Butoxy) andIn one or more replaced, when there is multiple substituent group, described substituent group can With identical or different；X is halogen (such as chlorine, bromine or iodine, preferably chlorine or bromine)；R8、R9、R10And R11Point Wei hydrogen or C1～C3Alkyl (such as methyl, ethyl, propyl group or isopropyl, preferably methyl)；R12And R13 It is respectively hydrogen, C1～C3Alkyl (such as methyl, ethyl, propyl group or isopropyl, preferably methyl), C5～C10 Aryl (such as phenyl) or R12、R13And the carbon atom that they are connected is collectively forming 4-6 membered cyclic structure (described six-membered cyclic structure is such as)。
R1For " substituted or unsubstituted C3～C15Aryl " (preferably " substituted or unsubstituted C5～C14Aryl ", Described " substituted or unsubstituted C5～C14Aryl " preferably " substituted or unsubstituted phenyl ", " replace or do not take The naphthyl in generation " or " substituted or unsubstituted fluorenyl "；Described " unsubstituted naphthyl " such asDescribed " unsubstituted fluorenyl " such asDescribed " substituted fluorenyl " such as Described " substituted phenyl " is preferred4-tert-butyl-phenyl,4-cyano-phenyl, 3-fluoro-4-cyano-phenyl, 3-cyano-phenyl,3,4-Dichlorobenzene base,4-Phenoxyphenyl, 4-trifluoromethyl, 3-trifluoromethyl, 4-trifluoromethyl Phenyl,2-aminomethyl phenyl, 3-aminomethyl phenyl, 4-methyl Phenyl,Or 3,5-Dichlorobenzene base；), " hetero atom is oxygen, sulfur or nitrogen-atoms, and hetero atom number is 1- 3, substituted or unsubstituted C2～C15Heteroaryl " (preferably " hetero atom is oxygen or nitrogen-atoms, hetero atom number It is the C of 13～C12Heteroaryl ", it is described that " hetero atom is oxygen or nitrogen-atoms, and hetero atom number is the C of 13~ C12Heteroaryl " preferably " substituted or unsubstituted pyridine radicals ", Described " unsubstituted pyridine radicals " can be 2-pyridine radicals, 3-pyridine radicals or 4-pyridine radicals；Institute " the substituted pyridine radicals " stated can be) orDescribed is " substituted or unsubstituted C3～C15Aryl " or " hetero atom is oxygen, sulfur or nitrogen-atoms, and hetero atom number is 1-3, replaces or unsubstituted C2～C15Heteroaryl " described in " replacement " be by cyano group, halogen (such as fluorine, chlorine, bromine or iodine), C1~ C10Alkyl (preferably C1～C6Alkyl, described " C1～C6Alkyl " such as methyl, ethyl, propyl group, different Propyl group, butyl, isobutyl group or the tert-butyl group), C1～C10Alkoxyl (preferably C1～C6Alkoxyl, described “C1～C6Alkoxyl " such as methoxyl group, ethyoxyl, propoxyl group, isopropoxy, butoxy, isobutoxy or uncle Butoxy), C5～C10Aryloxy group (preferably C5～C6Aryloxy group, described " C5～C6Aryloxy group " such as Phenoxy group), C1～C10Alkylthio group (preferably C1～C6Alkylthio group, described " C1～C6Alkylthio group " such as Methyl mercapto, ethylmercapto group, rosickyite base, isopropyisulfanyl, butylthio, isobutylthio or tertiary butylthio), C1～C10's Alkyl silyl (preferably C1～C6Alkyl silyl, described " C1～C6Alkyl silyl " such as methylsilyl, three Methylsilyl, ethyl are silica-based, propyl group is silica-based, isopropyl is silica-based, butyl is silica-based, isobutyl group is silica-based or the tert-butyl group is silica-based), " the C of halogen substiuted1～C10Alkyl " (described " C of halogen substiuted1～C10Alkyl " described in halogen excellent Selecting fluorine, chlorine or bromine, the number of described halogen is 1-4, and when there is multiple halogen atom, described halogen is former Son can be identical or different；Described " the C of halogen substiuted1～C10Alkyl " described in " C1～C10Alkyl " Preferably C1～C6Alkyl, described " C1～C6Alkyl " can be methyl, ethyl, propyl group, isopropyl, fourth Base, isobutyl group or the tert-butyl group.Described " the C of halogen substiuted1～C10Alkyl " preferably " in fluorine, chlorine and bromine atoms One or more substituted C1～C6Alkyl ", described " the one or more replacements in fluorine, chlorine and bromine atoms C1～C6Alkyl " preferably " the one or more substituted methyl in fluorine, chlorine and bromine atoms ", " fluorine, chlorine and bromine One or more substituted ethyl in atom ", " the one or more substituted propyl group in fluorine, chlorine and bromine atoms ", " the one or more substituted isopropyl in fluorine, chlorine and bromine atoms ", " one or more in fluorine, chlorine and bromine atoms Substituted butyl ", " the one or more substituted isobutyl group in fluorine, chlorine and bromine atoms " or " in fluorine, chlorine and bromine atoms The one or more substituted tert-butyl group "；Described " the substituted methyl of fluorine atom " preferably trifluoromethyl), " halogen takes The C in generation1～C10Alkoxyl " (described " C of halogen substiuted1～C10Alkoxyl " described in halogen preferred Fluorine, chlorine or bromine, the number of described halogen is 1-4, when there is multiple halogen atom, described halogen atom Can be identical or different；Described " the C of halogen substiuted1～C10Alkoxyl " described in " C1～C10Alkyl " Preferably C1～C6Alkyl, described " C1～C6Alkyl " can be methyl, ethyl, propyl group, isopropyl, fourth Base, isobutyl group or the tert-butyl group.Described " the C of halogen substiuted1～C10Alkoxyl " preferably " fluorine, chlorine and bromine atoms In one or more substituted C1～C6Alkoxyl ", described " one or more in fluorine, chlorine and bromine atoms Substituted C1～C6Alkoxyl " preferably " the one or more substituted methoxyl group in fluorine, chlorine and bromine atoms ", " fluorine, One or more substituted ethyoxyl in chlorine and bromine atoms ", " one or more substituted in fluorine, chlorine and bromine atoms Propoxyl group ", " the one or more substituted isopropoxy in fluorine, chlorine and bromine atoms ", " in fluorine, chlorine and bromine atoms One or more substituted butoxy ", " the one or more substituted isobutoxy in fluorine, chlorine and bromine atoms " or " fluorine, One or more substituted tert-butoxy in chlorine and bromine atoms "；Described " the substituted methoxyl group of fluorine atom " preferably three Fluorine methoxyl group), C3～C10Aryl (preferably C3～C6Aryl, described " C3～C6Aryl " preferred benzene Base),(such as)、(such as)、(such as)、(preferablyOne or more in) are replaced, when there is multiple substituent group, Described substituent group is identical or different；Wherein, R3、R4、R6And R7The most independent for hydrogen atom or C1～C6Alkane Base (such as methyl, ethyl, propyl group, isopropyl, butyl, isobutyl group or the tert-butyl group)；R5For hydrogen atom, C1~ C6Alkyl (such as methyl, ethyl, propyl group, isopropyl, butyl, isobutyl group or the tert-butyl group) or " hetero atom is Nitrogen-atoms, hetero atom number are the C of 1-23～C6Heterocyclylalkyl " (described " hetero atom is nitrogen-atoms, miscellaneous former Subnumber is the C of 1-23～C6Heterocyclylalkyl " preferably " and hetero atom be nitrogen-atoms, hetero atom number be the C of 13~ C4Heterocyclylalkyl ", described " hetero atom be nitrogen-atoms, hetero atom number be the C of 13～C4Heterocyclylalkyl " Such as)。
R2For H or substituted or unsubstituted C1～C10Alkyl (described " unsubstituted C1～C10Alkyl " Such as methyl, ethyl, propyl group, butyl, amyl group, hexyl, heptyl, nonyl or decyl；Described " substituted C1~ C10Alkyl " the most substituted methyl, substituted ethyl, substituted propyl group, substituted butyl, substituted amyl group, Substituted hexyl, substituted heptyl, substituted nonyl or substituted decyl；Described " substituted methyl " such asDescribed " substituted propyl group " such as)；Described " substituted or unsubstituted C1~ C10Alkyl " described in replacement refer to by C5～C10Aryl (preferably phenyl) replaced.
In the present invention, described compound A () further preferred following arbitrary compound:
In the present invention, TMS represents that trimethyl is silica-based.
In the present invention, described compoundFurther preferred following arbitrary compound:
In the present invention, described compoundFurther preferred following arbitrary compound:
In the described preparation method containing the compound of a fluoroalkyl, described solvent can be in this area such The Conventional solvents of Suzuki coupling reaction, particularly preferred ether solvent in the present invention, alcohols solvent, chlorinated hydrocarbon are molten One or more in agent, aromatic hydrocarbon solvent and sulfoxide type solvents, further preferred ether solvent.Described ethers is molten The preferred glycol dimethyl ether of agent (DME) and/or Isosorbide-5-Nitrae-dioxane.The preferred isopropanol of described alcohols solvent.Institute The aromatic hydrocarbon solvent stated can be toluene；Described sulfoxide type solvents can be dimethyl sulfoxide；Described chlorinated hydrocarbon Solvent can be 1,2-dichloroethanes.
In the described preparation method containing the compound of a fluoroalkyl, described solvent and the body of described compound B Long-pending preferred 1mL/mmol～100mL/mmol of mol ratio, further preferred 1mL/mmol～10mL/mmol.
In the described preparation method containing the compound of a fluoroalkyl, described alkali can be in this area such The conventional alkaline of Suzuki coupling reaction, particularly preferred alkali metal hydroxide, alkali carbonate, alkali gold in the present invention Belong to bicarbonate, alkali metal phosphate or " alkali metal and C1～C4The salt that alcohol is formed "；Described alkali carbonate is excellent Select one or more in potassium carbonate, sodium carbonate and cesium carbonate, further preferred potassium carbonate and/or sodium carbonate, then enter The one preferred potassium carbonate of step.Described alkali metal phosphate preferably phosphoric acid potassium.Described " alkali metal and C1～C4Alcohol is formed Salt " described in " C1～C4Alcohol " preferably methanol, ethanol, propanol, isopropanol or the tert-butyl alcohol；Described " alkali gold Belong to and C1～C4The salt that alcohol is formed " described in " alkali metal " preferably lithium, sodium, potassium, rubidium or caesium；Described " alkali gold Belong to and C1～C4The salt that alcohol is formed " preferred tert-butyl alcohol lithium.
In the described preparation method containing the compound of a fluoroalkyl, described alkali and described compound B mole Ratio preferably 1～5, further preferred 2～3.
In the described preparation method containing the compound of a fluoroalkyl, described part can be in this area such The conventional ligands of suzuki coupling reaction, in the present invention, particularly preferred nitrogenous bidentate ligand or nitrogenous tridentate ligand, described " nitrogenous bidentate ligand " preferred substituted or unsubstituted bipyridyl (described " substituted bipyridyl " is preferred ), substituted or unsubstituted 1, (described " unsubstituted 1,10-phenanthrene quinoline " is excellent for 10-phenanthrene quinoline ChoosingDescribed " substituted 1,10-phenanthrene quinoline " is preferred) or(such as ).(described is " substituted for described nitrogenous tridentate ligand preferably " substituted or unsubstituted pyridine " Pyridine " preferably), described " substituted or unsubstituted bipyridyl ", " replacement or unsubstituted 1,10-phenanthrene quinoline " or " replace or substituted pyridine " described in " replacement " refer in heteroatomic non-ortho by C1~ C10Alkyl (preferably C1～C6Alkyl, described " C1～C6Alkyl " the most such as methyl, ethyl, third Base, isopropyl, butyl, isobutyl group or the tert-butyl group), C1～C10Alkoxyl (preferably C1～C6Alkoxyl, Described " C1～C6Alkoxyl " such as methoxyl group, ethyoxyl, propoxyl group, isopropoxy, butoxy, isobutyl oxygen Base or tert-butoxy) andIn one or more replaced, when there is multiple substituent group, described takes Can be identical or different for base；R8、R9、R10And R11It is respectively hydrogen or C1～C3Alkyl (such as methyl, second Base, propyl group or isopropyl)；R12And R13It is respectively hydrogen, C1～C3Alkyl (such as methyl, ethyl, propyl group Or isopropyl), C5～C10Aryl (such as phenyl) or R12、R13And carbon atom that they are connected is common (described six-membered cyclic structure is such as to form 4-6 membered cyclic structure)。
In the described preparation method containing the compound of a fluoroalkyl, described part is further preferred The most preferred
In the described preparation method containing the compound of a fluoroalkyl, described part rubs with described compound B's That ratio preferably 0.01～0.1, further preferred 0.05～0.1.
In the described preparation method containing the compound of a fluoroalkyl, described nickel salt preferred dimethyl second diether closes chlorination Nickel (NiCl2DME), 1,2 pairs of (diphenylphosphine) ethane close Nickel dichloride. (NiCl2Dppe), Nickel dichloride. (NiCl2)、 Nickelous bromide (NiBr2), Nickel diiodide. (NiI2), Nickel dichloride hexahydrate (NiCl2·6H2O), three hydration nickelous bromide (NiBr2·3H2O)、 Nickel acetate (Ni (OAc)2), nickel acetylacetonate (Ni (acac)2), two triphenylphosphines close Nickel dichloride. (NiCl2(PPh3)2) or six Nitric hydrate nickel (Ni (NO3)2·6H2O)；Further preferably dimethyl second diether closes Nickel dichloride. (NiCl2DME), six water Close nickel nitrate (Ni (NO3)2·6H2O) or 1,2 pairs of (diphenylphosphine) ethane close Nickel dichloride. (NiCl2Then enter dppe), One step preferred dimethyl second diether closes Nickel dichloride. (NiCl2·DME)。
In the described preparation method containing the compound of a fluoroalkyl, described catalyst is with described compound B's Molar ratio preferably 0.01～0.1, further preferred 0.05～0.1.
In the described preparation method containing the compound of a fluoroalkyl, the preferred pyridine of described additive, 4-fluoroform Yl pyridines, 4-picoline, 2,6-lutidines, DMAP (DMAP) and 4-methoxypyridine (4-MeO-Py) one or more in, further preferred DMAP (DMAP) and/or 4-methoxy Yl pyridines (4-MeO-Py), further preferred DMAP (DMAP).
In the described preparation method containing the compound of a fluoroalkyl, described compound A and described compound B Molar ratio preferably 0.5～2, further preferred 0.75～1.5.
In the described preparation method containing the compound of a fluoroalkyl, described additive is with described compound B's Molar ratio preferably 0.01～0.1, further preferred 0.05～0.1.
In the described preparation method containing the compound of a fluoroalkyl, the temperature of described Suzuki coupling reaction is preferred 20 DEG C～120 DEG C, further preferred 70 DEG C～80 DEG C.
In the described preparation method containing the compound of a fluoroalkyl, the process of described Suzuki coupling reaction is permissible The common detection methods (such as TLC, HPLC or NMR) in this area is used to be monitored, typically with chemical combination Thing B is reaction end when disappearing, preferably 1 hour～48 hours response time, further preferred 8 hours～24 little Time.
Present invention also offers the compound as shown in formula C,
R1CHR2F
C
Wherein, R1And R2Definition the most same as above.
Present invention also offers described compound C application in preparation medicine, pesticide or medical material.The present invention's Compound C due to the character (such as: metabolic stability, fat-soluble etc.) of its uniqueness, can be widely used in medicine, In pesticide or field of medical materials, the situation that such as documents below is reported: (a) T.Hiyama.Organofluorine Compounds:Chemistry and Applications, Springer, New York, 2000. (b) W.K.Hagmann, J. Med.Chem.2008,51,4359. (c) C.Ni, L.Zhu, J.Hu, Acta Chim.Sinica.2015,78,90. (d) D.O ' Hagan.Chem.Soc.Rev.2008,37,308.
In the present invention, the when of not specifying, described " alkyl " for include having appointment carbon number purpose side chain or The representative examples of saturated aliphatic alkyl of straight chain；As at " C1～C20Alkyl " defined in for be included in straight chain or branched structure have 1, 2,3,4,5,6,7,8,9,11,11,12,13,14,15,16,17,18,19 or 20 carbon atoms Group.Such as, " C1～C10Alkyl " specifically include methyl, ethyl, n-pro-pyl, isopropyl, normal-butyl, the tert-butyl group, Isobutyl group, amyl group, hexyl, heptyl, octyl group, nonyl and decyl etc..
In the present invention, the when of not specifying, described " alkoxyl " represent alkyl be connected with oxygen atom after generation base Group, i.e. "", R is alkyl.
In the present invention, the when of not specifying, described " alkylthio group " represent alkyl be connected with sulphur atom after generation base Group, i.e. "", R is alkyl.
In the present invention, the when of not specifying, described " alkyl silyl " is structureIn, R1’、R2’And R3’ In at least one be alkyl, remaining is the group of hydrogen.
In the present invention, the when of not specifying, described " Heterocyclylalkyl " at this individually or as the one of another group When part uses, refer to comprise 4～12 yuan of monocycles of 1～4 hetero atom (such as one or more in nitrogen, oxygen and sulfur) or Polycyclic moiety, the most each ring can contain one or more double bonds, but neither one ring has the pi-electron of total conjugated System.Additionally, any heterocycloalkyl ring can condense on cycloalkyl, aryl, heteroaryl or heterocycloalkyl ring.Fixed at this Heterocyclylalkyl in the range of justice includes but not limited to: oxazoline, oxygen cyclobutyl, pyranose, THP trtrahydropyranyl, azetidin Alkyl, Isosorbide-5-Nitrae-dialkyl group, hexahydro azatropylidene base, piperazinyl, piperidyl, pyrrolidinyl, morpholinyl, thio-morpholinyl, Dihydrofuran base, glyoxalidine base, indolinyl, dihydro isoxazolyl, dihydro isothiazolyl, dihydrooxadiazole base, Dihydro oxazolyl, dihydro pyrazinyl, pyrazoline base, dihydropyridine base, dihydro-pyrimidin base, pyrrolin base, dihydro four Oxazolyl, thiodiazoline base, dihydro-thiazolyl, dihydro-thiophene base, dihydro triazolyl, dihydro azetidinyl, tetrahydrochysene Furyl and tetrahydro-thienyl and N-oxide thereof.Heterocyclylalkyl can be through carbon atom therein or hetero atom and other bases Group is attached.
In the present invention, the when of not specifying, described " aryl " refers to any stable may be up to 7 in each ring The monocycle of atom or bicyclic carbocyclic, at least one of which ring is aromatic rings；The example of above-mentioned aryl unit include phenyl, Naphthyl, tetralyl, 2,3-indanyl, xenyl, phenanthryl, anthryl or acenaphthenyl (acenaphthyl).Can manage Solving, be two ring substituents at aryl substituent, and one of them ring is in the case of non-aromatic ring, connection is to pass through aromatic ring Carry out.
In the present invention, the when of not specifying, described " aryloxy group " represent by oxygen bridging connect to have described carbon former Subnumber purpose aryl.Thus, " aryloxy group " comprises the definition of above aryl.
In the present invention, the when of not specifying, described " heteroaryl " represents and may be up to the steady of 7 atoms in each ring Order ring or bicyclo-, at least one of which ring is aromatic rings and contains 1-4 the hetero atom selected from O, N and S； Heterocyclic aryl within the range defined herein includes but not limited to: acridinyl, carbazyl, cinnolines base, quinoxalinyl, pyrazoles Base, indyl, benzotriazole base, furyl, thienyl, benzothienyl, benzofuranyl, quinolyl, isoquinolin Base, oxazolyl, isoxazolyl, indyl, pyrazinyl, pyridazinyl, pyridine radicals, pyrimidine radicals, pyrrole radicals, tetrahydroquinoline. As the definition of following heterocycle, " heterocyclic aryl " it should also be understood that the N-oxide being to include any nitrogen-containing hetero aryl spreads out Biological.Heterocyclic aryl substituent group is two ring substituents and a ring is non-aromatic ring or does not comprise heteroatomic wherein In the case of, it will be understood that connect and by aromatic ring or carry out by comprising the hetero atom of ring respectively.
In the present invention, the when of not specifying, described " halogen " represents fluorine, chlorine, bromine, iodine or astatine.
In the present invention, the described " C determining carbon number rangex1～Cy1" substituent group (x1 and y1 is integer), such as " Cx1~ Cy1" alkyl, " Cx1～Cy1" alkoxyl, " Cx1～Cy1" aryl, " Cx1～Cy1" heteroaryl or " Cx1～Cy1” Alkoxy carbonyl, all represent the carbon number not comprising substituent group, such as C1～C10Alkyl represents the C not comprising substituent group1~ C10Alkyl.
Without prejudice to the field on the basis of common sense, above-mentioned each optimum condition, can combination in any, obtain the present invention each preferably Example.
Agents useful for same of the present invention and raw material are the most commercially.
In the present invention, described room temperature refers to ambient temperature, is 10 DEG C～35 DEG C.
The actively progressive effect of the present invention is: the preparation method of the present invention by single step reaction just can introduce a fluoroalkyl, High-efficient simple, functional group compatibility are good, broad spectrum activity is strong, can avoid using poisonous reagent, post-processing operation simple and safe, Environmental friendliness, catalyst are cheap and consumption is low, reaction condition is gentle, reaction conversion ratio is high, yield is high, production cost Low, be suitable for industrialized production.The compound containing a fluoroalkyl that the present invention prepares due to its uniqueness character (such as: Metabolic stability, fat-soluble etc.) it is widely used in preparation medicine, pesticide or medical material, marketization prospect Well.
Detailed description of the invention
Further illustrate the present invention below by the mode of embodiment, but the most therefore limit the present invention to described enforcement Among example scope.The experimental technique of unreceipted actual conditions in the following example, conventionally and condition, or according to Catalogue selects.
The raw material used in the embodiment of the present invention is the most commercially, it is also possible to list of references X.Jiang, S.akthivel, K. Kulbitski, G.Nisnevich, M.Gandelman.J.Am.Chem.Soc.2014,136, the method for 9548-9551. report Prepare.
Embodiment 1
In the reaction tube of 25mL, add 178mg (0.9mmol) 4-biphenylboronic acid, 6.6mg (5mol%, mol% Refer to NiCl2DME and the percentage ratio of compound B mole) NiCl2DME (dimethyl second diether closes Nickel dichloride .), The 5.4mg percentage ratio of phen and compound B mole (5mol%, the mol% refer to) phen (1,10 '-phenanthroline), 7.4 The mg percentage ratio of DMAP and compound B mole (5mol%, the mol% refer to) DMAP (DMAP), 166mg(1.2mmol)K2CO3, 2mL glycol dimethyl ether, 1.7mL Isosorbide-5-Nitrae-dioxane, inject 300uL CH2Isosorbide-5-Nitrae-the dioxane solution (concentration: 2M, 0.6mmol) of FBr, after stirring 24 hours, separates and produces at 70 DEG C Rate is 90%, and purity is identified more than 95% through hydrogen spectrum.1H NMR (400MHz, CDCl3) δ 7.61-7.69 (m, 4H), 7.45-7.52 (m, 4H), 7.40 (t, J=7.3Hz, 1H), 5.45 (d, J=47.9Hz, 2H).13C NMR (100MHz, CDCl3) δ 141.7 (d, J=3.2Hz), 140.6 (d, J=1.1Hz), 135.1 (d, J=17.1Hz), 128.8,128.0 (d, J =5.7Hz), 127.5,127.3 (d, J=1.4Hz), 127.1 (d, J=0.5Hz), 84.4 (d, J=166.0Hz).19F NMR (376MHz, CDCl3) δ-206.2 (t, J=47.9Hz, 1F).
Embodiment 2
In the reaction tube of 25mL, addition 195mg (0.9mmol) 2-fluorine xenyl-4-boric acid, 6.6mg (5mol%, Mol% refers to NiCl2DME and the percentage ratio of compound B mole) NiCl2(dimethyl second diether closes chlorination to DME Nickel), the 5.4mg percentage ratio of phen and compound B mole (5mol%, the mol% refer to) phen (1,10 '-phenanthroline), The 7.4mg percentage ratio of DMAP and compound B mole (5mol%, the mol% refer to) DMAP (4-dimethylamino pyrrole Pyridine), 166mg (1.2mmol) K2CO3, 2mL glycol dimethyl ether, 1.7mL Isosorbide-5-Nitrae-dioxane, inject 300uL CH2Isosorbide-5-Nitrae-the dioxane solution (concentration: 2M, 0.6mmol) of FBr, after stirring 24 hours, separates productivity at 70 DEG C Being 83%, purity is identified more than 95% through hydrogen spectrum.1H NMR (400MHz, CDCl3) δ 7.58-7.53 (m, 2H), 7.50 -7.44 (m, 3H), 7.43-7.37 (m, 1H), 7.24-7.17 (m, 2H), 5.42 (d, J=47.5Hz, 1H).13C NMR (125.7MHz, CDCl3) δ 159.7 (d, J=249.0Hz), 137.5 (dd, J=17.6,7.7Hz), 135.3,131.0 (dd, J =3.8,0.8Hz), 129.3 (dd, J=13.7,2.8Hz), 129.0 (d, J=2.9Hz), 128.5,127.9,123.0 (dd, J= 6.1,3.7Hz), 114.9 (dd, J=23.9,6.4Hz), 83.5 (dd, J=168.0,1.6Hz).19F NMR (376MHz, CDCl3) δ-117.4--117.7 (m, 1F) ,-209.3 (t, J=47.5Hz, 1F) .IR (membrane process) vmax3034,2926, 2361,1583,1421,1274,1011cm-1.MS (EI): m/z (%) 204 (M+, 100), 183,170,127.HRMS: Calculated for (theoretical value) C13H10F2: 204.0751；Found (measured value): 204.0750.
Embodiment 3
In the reaction tube of 25mL, addition 178mg (0.9mmol) 3-biphenylboronic acid, 13.2mg (10mol%, Mol% refers to NiCl2DME and the percentage ratio of compound B mole) NiCl2(dimethyl second diether closes chlorination to DME Nickel), and the 10.8mg percentage ratio of phen and compound B mole (10mol%, the mol% refer to) phen (1,10 '-Féraud Quinoline), the 14.4mg percentage ratio of DMAP and compound B mole (10mol%, the mol% refer to) DMAP (4-diformazan Aminopyridine), 166mg (1.2mmol) K2CO3, 2mL glycol dimethyl ether, 1.7mL Isosorbide-5-Nitrae-dioxane, note Penetrate 300uL CH2Isosorbide-5-Nitrae-the dioxane solution (concentration: 2M, 0.6mmol) of FBr, after stirring 24 hours at 70 DEG C, Separating productivity is 90%, and purity is identified more than 95% through hydrogen spectrum.1H NMR (400MHz, CDCl3)δ7.67-7.60 (m, 4H), 7.54-7.46 (m, 3H), 7.44-7.38 (m, 2H), 5.48 (d, J=47.8Hz, 2H).13C NMR (125.7MHz, CDCl3) δ 141.6 (d, J=1.3Hz), 140.7,136.7 (d, J=17.1Hz), 129.0 (d, J= 1.1Hz), 128.8,127.56,127.54 (d, J=2.0Hz), 127.1,126.3 (d, J=5.8Hz), 126.2 (d, J= 5.9Hz), 84.6 (d, J=166.5Hz).19F NMR (376MHz, CDCl3) δ-207.3 (t, J=47.9Hz, 1F). IR (membrane process) vmax3033,1598,1481,1241,1028cm-1.MS (EI): m/z (%) 186 (100), 165, 152,109.HRMS:Calculated for (theoretical value) C13H11F:186.0845；Found (measured value): 186.0841.
Embodiment 4
In the reaction tube of 25mL, addition 160mg (0.9mmol) 4-tert-butylbenzeneboronic acid, 6.6mg (5mol%, Mol% refers to NiCl2DME and the percentage ratio of compound B mole) NiCl2(dimethyl second diether closes chlorination to DME Nickel), the 5.4mg percentage ratio of phen and compound B mole (5mol%, the mol% refer to) phen (1,10 '-phenanthroline), The 7.4mg percentage ratio of DMAP and compound B mole (5mol%, the mol% refer to) DMAP (4-dimethylamino pyrrole Pyridine), 166mg (1.2mmol) K2CO3, 2mL glycol dimethyl ether, 1.7mL Isosorbide-5-Nitrae-dioxane, inject 300uL CH2Isosorbide-5-Nitrae-the dioxane solution (concentration: 2M, 0.6mmol) of FBr, after stirring 24 hours, separates productivity at 70 DEG C Being 75%, purity is identified more than 95% through hydrogen spectrum.1H NMR (400MHz, CDCl3) δ 7.46 (d, J=7.9Hz, 2H), 7.36 (dd, J=8.3Hz, 1.8Hz, 2H), 5.38 (d, J=48.1Hz, 2H), 1.37 (s, 9H).13C NMR(125.7 MHz, CDCl3) δ 151.9 (d, J=3.4Hz), 133.2 (d, J=17.2Hz), 127.6 (d, J=5.3Hz), 125.5 (d, J =1.9Hz), 84.5 (d, J=165.0Hz), 34.7,31.3.19F NMR (376MHz, CDCl3) δ-204.4 (t, J=48.1 Hz, 1F).
Embodiment 5
In the reaction tube of 25mL, addition 175mg (0.9mmol) 4-carbethoxyl group phenylboric acid, 6.6mg (5mol%, Mol% refers to NiCl2DME and the percentage ratio of compound B mole) NiCl2(dimethyl second diether closes chlorine to DME Change nickel), and the 5.4mg percentage ratio of phen and compound B mole (5mol%, the mol% refer to) phen (1,10 '-Féraud Quinoline), the 7.4mg percentage ratio of DMAP and compound B mole (5mol%, the mol% refer to) DMAP (4-diformazan ammonia Yl pyridines), 166mg (1.2mmol) K2CO3, 2mL glycol dimethyl ether, 1.7mL Isosorbide-5-Nitrae-dioxane, inject 300 uL CH2Isosorbide-5-Nitrae-the dioxane solution (concentration: 2M, 0.6mmol) of FBr, after stirring 24 hours, separates and produces at 70 DEG C Rate is 74%, and purity is identified more than 95% through hydrogen spectrum.1H NMR (400MHz, CDCl3) δ 8.07 (d, J=7.7Hz, 2 H), 7.43 (d, J=7.4Hz, 2H), 5.45 (d, J=47.2Hz, 2H), 4.39 (q, J=7.1Hz, 2H), 1.40 (t, J= 7.1Hz, 3H).13C NMR (101MHz, CDCl3) δ 166.1,141.0 (d, J=17.2Hz), 130.6 (d, J=2.3Hz), 129.7,126.5 (d, J=6.5Hz), 83.6 (d, J=168.4Hz), 61.0,14.2.19F NMR (376MHz, CDCl3)δ- 212.7 (t, J=47.2Hz, 1F) .IR (membrane process) vmax2983,1716,1418,1310,1106,1021cm-1.MS (EI): M/z (%) 182 (M+), 154,137 (100) .HRMS:Calculated for (theoretical value) C10H11FO2: 182.0743；Found (measured value): 182.0739.
Gram level synthesis: in the reaction tube of 100mL, adds 2.91g (15mmol) 4-carbethoxyl group phenylboric acid, 110mg (5mol%, mol% refer to NiCl2DME and the percentage ratio of compound B mole) NiCl2DME (dimethyl second Diether closes Nickel dichloride .), the 90mg percentage ratio of phen and compound B mole (5mol%, the mol% refer to) phen (1,10 '-phenanthroline), the 122mg percentage ratio of DMAP and compound B mole (5mol%, the mol% refer to) DMAP (DMAP), 2.76g (20mmol) K2CO3, 33mL glycol dimethyl ether, 28mL Isosorbide-5-Nitrae-dioxane, Injection 5mL CH2Isosorbide-5-Nitrae-the dioxane solution (concentration: 2M, 0.6mmol) of FBr, after stirring 24 hours at 70 DEG C, Separating productivity is 78%, and purity is identified more than 95% through hydrogen spectrum.
Embodiment 6
In the reaction tube of 25mL, addition 175mg (0.9mmol) 3-carbethoxyl group phenylboric acid, 6.6mg (5mol%, Mol% refers to NiCl2DME and the percentage ratio of compound B mole) NiCl2(dimethyl second diether closes chlorine to DME Change nickel), and the 5.4mg percentage ratio of phen and compound B mole (5mol%, the mol% refer to) phen (1,10 '-Féraud Quinoline), the 7.4mg percentage ratio of DMAP and compound B mole (5mol%, the mol% refer to) DMAP (4-diformazan ammonia Yl pyridines), 166mg (1.2mmol) K2CO3, 2mL glycol dimethyl ether, 1.7mL Isosorbide-5-Nitrae-dioxane, inject 300 uL CH2Isosorbide-5-Nitrae-the dioxane solution (concentration: 2M, 0.6mmol) of FBr, after stirring 24 hours, separates and produces at 70 DEG C Rate is 42%, and purity is identified more than 95% through hydrogen spectrum.1H NMR (400MHz, CDCl3) δ 8.07-8.01 (m, 2H), 7.56 (d, J=7.8Hz, 1H), 7.47 (t, J=7.7Hz, 1H), 5.42 (d, J=47.5Hz, 2H), 4.38 (q, J=7.1 Hz, 2H), 1.40 (t, J=7.1Hz, 3H).13C NMR (101MHz, CDCl3) δ 166.1,136.5 (d, J=17.5Hz), 131.5 (d, J=5.8Hz), 130.8,129.7 (d, J=2.5Hz), 128.6,128.3 (d, J=6.2Hz), 83.9 (d, J=167.5 Hz), 61.1,14.2.19F NMR (376MHz, CDCl3) δ-208.9 (t, J=47.6Hz, 1F) .IR (membrane process) vmax 2983,1719,1447,1286,1107cm-1.MS (EI): m/z (%) 182 (M+), 154,137 (100) .HRMS: Calculated for (theoretical value) C10H11FO2: 182.0743；Found (measured value): 182.0740.
Embodiment 7
In the reaction tube of 25mL, addition 148mg (0.9mmol) 4-acetylbenzene boric acid, 6.6mg (5mol%, Mol% refers to NiCl2DME and the percentage ratio of compound B mole) NiCl2(dimethyl second diether closes chlorine to DME Change nickel), and the 5.4mg percentage ratio of phen and compound B mole (5mol%, the mol% refer to) phen (1,10 '-Féraud Quinoline), the 7.4mg percentage ratio of DMAP and compound B mole (5mol%, the mol% refer to) DMAP (4-diformazan ammonia Yl pyridines), 166mg (1.2mmol) K2CO3, 2mL glycol dimethyl ether, 1.7mL Isosorbide-5-Nitrae-dioxane, inject 300 uL CH2Isosorbide-5-Nitrae-the dioxane solution (concentration: 2M, 0.6mmol) of FBr, after stirring 24 hours, separates and produces at 70 DEG C Rate is 73%, and purity is identified more than 95% through hydrogen spectrum.1H NMR (400MHz, CDCl3) δ 7.96 (d, J=7.6Hz, 2 H), 7.43 (dd, J=7.9Hz, 0.6Hz, 2H), 5.43 (d, J=47.2Hz, 2H), 2.59 (s, 3H).13C NMR(125.7 MHz, CDCl3) δ 197.5,141.3 (d, J=17.0Hz), 137.0 (d, J=2.4Hz), 128.5,126.7 (d, J=6.7Hz), 83.5 (d, J=168.4Hz), 26.5.19F NMR (376MHz, CDCl3) δ-213.1 (t, J=47.1Hz, 1F) .IR is (thin Embrane method) vmax2961,2041,1685,1612,1414,1267,1012cm-1.MS (EI): m/z (%) 152 (M+), 149, 137 (100), 109,83.HRMS:Calculated for (theoretical value) C9H9FO:152.0637；Found (measured value): 152.0635.
Embodiment 8
In the reaction tube of 25mL, addition 135mg (0.9mmol) 3-formylphenylboronic acid, 13.2mg (10mol%, Mol% refers to NiCl2DME and the percentage ratio of compound B mole) NiCl2(dimethyl second diether closes chlorine to DME Change nickel), the 10.8mg percentage ratio of phen and compound B mole (10mol%, the mol% refer to) phen (1,10 '-phenanthrene Sieve quinoline), the 14.4mg percentage ratio of DMAP and compound B mole (10mol%, the mol% refer to) DMAP (4-bis- Methylamino pyridine), 166mg (1.2mmol) K2CO3, 2mL glycol dimethyl ether, 1.7mL Isosorbide-5-Nitrae-dioxane, note Penetrate 300uL CH2Isosorbide-5-Nitrae-the dioxane solution (concentration: 2M, 0.6mmol) of FBr, after stirring 24 hours at 70 DEG C, Separating productivity is 80%, and purity is identified more than 95% through hydrogen spectrum.1H NMR (400MHz, CDCl3) δ 10.05 (s, 1H), 7.91-7.86 (m, 2H), 7.65 (d, J=7.6Hz, 1H), 7.58 (t, J=7.5Hz, 1H), 5.47 (d, J=47.3Hz, 2 H).13C NMR (125.7MHz, CDCl3) δ 191.8,137.3 (d, J=17.7Hz), 136.6,132.9 (d, J=5.9Hz), 129.9 (d, J=2.4Hz), 129.3,128.0 (d, J=6.3Hz), 83.5 (d, J=168.2Hz).19F NMR (376MHz, CDCl3) δ-212.7 (t, J=47.2Hz, 1F) .IR (membrane process) vmax2918,2849,1685,1420,1089cm-1.MS (EI): m/z (%) 138 (M+), 137,109 (100), 83.HRMS:Calculated for (theoretical value) C8H7FO:138.0481； Found (measured value): 138.0477.
Embodiment 9
In the reaction tube of 25mL, addition 135mg (0.9mmol) 4-formylphenylboronic acid, 6.6mg (5mol%, Mol% refers to NiCl2DME and the percentage ratio of compound B mole) NiCl2(dimethyl second diether closes chlorine to DME Change nickel), and the 5.4mg percentage ratio of phen and compound B mole (5mol%, the mol% refer to) phen (1,10 '-Féraud Quinoline), the 7.4mg percentage ratio of DMAP and compound B mole (5mol%, the mol% refer to) DMAP (4-diformazan ammonia Yl pyridines), 166mg (1.2mmol) K2CO3, 2mL glycol dimethyl ether, 1.7mL Isosorbide-5-Nitrae-dioxane, inject 300 uL CH2Isosorbide-5-Nitrae-the dioxane solution (concentration: 2M, 0.6mmol) of FBr, after stirring 24 hours, separates and produces at 70 DEG C Rate is 67%, and purity is identified more than 95% through hydrogen spectrum.1H NMR (500MHz, CDCl3) δ 10.02 (s, 1H), 7.90 (d, J=7.5Hz, 2H), 7.52 (d, J=7.8Hz, 2H), 5.47 (d, J=47.0Hz, 2H).13C NMR (125.7MHz, CDCl3) δ 191.7,142.8 (d, J=17.1Hz), 136.3 (d, J=2.1Hz), 129.9,126.9 (d, J=6.9Hz), 83.4 (d, J=169.4Hz).19F NMR (376MHz, CDCl3) δ-214.2 (t, J=47.0Hz, 1F) .IR (membrane process) vmax 2958,2832,1701,1612,1426,1211cm-1.MS (EI): m/z (%) 138 (M+), 137 (100), 109,83.HRMS: Calculated for (theoretical value) C8H7FO:138.0481；Found (measured value): 138.0477.
Embodiment 10
In the reaction tube of 25mL, add 132mg (0.9mmol) 4-cyanophenylboronic acid, 6.6mg (5mol%, mol% Refer to NiCl2DME and the percentage ratio of compound B mole) NiCl2DME (dimethyl second diether closes Nickel dichloride .), The 5.4mg percentage ratio of phen and compound B mole (5mol%, the mol% refer to) phen (1,10 '-phenanthroline), 7.4 The mg percentage ratio of DMAP and compound B mole (5mol%, the mol% refer to) DMAP (DMAP), 166mg(1.2mmol)K2CO3, 2mL glycol dimethyl ether, 1.7mL Isosorbide-5-Nitrae-dioxane, inject 300uL CH2FBr Isosorbide-5-Nitrae-dioxane solution (concentration: 2M, 0.6mmol), stir after 24 hours at 70 DEG C, separating productivity is 81%, Purity is identified more than 95% through hydrogen spectrum.1H NMR (500MHz, CDCl3) δ 7.67 (d, J=7.7Hz, 2H), 7.45 (dd, J=8.0Hz, 0.6Hz, 2H), 5.44 (d, J=46.9Hz, 2H).13C NMR (125.7MHz, CDCl3) δ 141.4 (d, J=17.5Hz), 132.3,126.9 (d, J=6.9Hz), 118.4,112.2 (d, J=2.4Hz), 83.0 (d, J=169.9Hz).19F NMR (376MHz, CDCl3) δ-215.1 (t, J=46.9Hz, 1F).
Embodiment 11
In the reaction tube of 25mL, addition 149mg (0.9mmol) 3-fluorine 4-cyanophenylboronic acid, 6.6mg (5mol%, Mol% refers to NiCl2DME and the percentage ratio of compound B mole) NiCl2(dimethyl second diether closes chlorine to DME Change nickel), and the 5.4mg percentage ratio of phen and compound B mole (5mol%, the mol% refer to) phen (1,10 '-Féraud Quinoline), the 7.4mg percentage ratio of DMAP and compound B mole (5mol%, the mol% refer to) DMAP (4-diformazan ammonia Yl pyridines), 166mg (1.2mmol) K2CO3, 2mL glycol dimethyl ether, 1.7mL Isosorbide-5-Nitrae-dioxane, inject 300 uL CH2Isosorbide-5-Nitrae-the dioxane solution (concentration: 2M, 0.6mmol) of FBr, after stirring 24 hours, separates and produces at 70 DEG C Rate is 73%, and purity is identified more than 95% through hydrogen spectrum.1H NMR (400MHz, CDCl3) δ 7.69-7.62 (m, 1H), 7.25 (s, 1H), 7.23-7.20 (m, 1H), 5.45 (d, J=46.5Hz, 2H).13C NMR (125.7MHz, CDCl3)δ 163.2 (d, J=260.1Hz), 144.7 (dd, J=18.4,7.8Hz), 133.8,122.1 (dd, J=7.4,3.6Hz), 114.0 (dd, J=20.9,8.1Hz), 113.6,101.2 (d, J=16.0Hz), 82.3 (dd, J=172.6,1.8Hz).19F NMR(376 MHz, CDCl3) δ-105.6 (dd, J=9.4,6.3Hz, 1F) ,-217.4 (t, J=46.6Hz, 1F) .IR (membrane process) vmax 3092,2962,2236,1625,1505,1430,1112,738cm-1.MS (EI): m/z (%) 153 (M+), 152 (100), 125, 107,75.HRMS:Calculated for (theoretical value) C8H5F2N:153.0390；Found (measured value): 153.0385.
Embodiment 12
In the reaction tube of 25mL, add 132mg (0.9mmol) 3-cyanophenylboronic acid, 6.6mg (5mol%, mol% Refer to NiCl2DME and the percentage ratio of compound B mole) NiCl2DME (dimethyl second diether closes Nickel dichloride .), The 5.4mg percentage ratio of phen and compound B mole (5mol%, the mol% refer to) phen (1,10 '-phenanthroline), 7.4 The mg percentage ratio of DMAP and compound B mole (5mol%, the mol% refer to) DMAP (DMAP), 166mg(1.2mmol)K2CO3, 2mL glycol dimethyl ether, 1.7mL Isosorbide-5-Nitrae-dioxane, inject 300uL CH2FBr Isosorbide-5-Nitrae-dioxane solution (concentration: 2M, 0.6mmol), stir after 24 hours at 70 DEG C, separating productivity is 70%, Purity is identified more than 95% through hydrogen spectrum.1H NMR (500MHz, CDCl3) δ 7.67-7.61 (m, 2H), 7.62-7.57 (m, 1H), 7.51 (t, J=7.7Hz, 1H), 5.41 (d, J=47.1Hz, 2H).13C NMR (125.7MHz, CDCl3)δ 137.7 (d, J=18.1Hz), 132.1 (d, J=2.4Hz), 131.1 (d, J=6.2Hz), 130.3 (d, J=7.0Hz), 129.4, 118.3,112.8,82.9 (d, J=169.5Hz).19F NMR (376MHz, CDCl3) δ-212.3 (t, J=47.0Hz, 1F). IR (membrane process) vmax3067,2960,2231,1607,1485,1000cm-1.MS (EI): m/z (%) 135 (M+), 134 (100), 115,107.HRMS:Calculated for (theoretical value) C8H6FN:135.0484；Found (measured value): 135.0483.
Embodiment 13
In the reaction tube of 25mL, addition 180mg (0.9mmol) 4-mesyl phenylboric acid, 6.6mg (5mol%, Mol% refers to NiCl2DME and the percentage ratio of compound B mole) NiCl2(dimethyl second diether closes chlorine to DME Change nickel), and the 5.4mg percentage ratio of phen and compound B mole (5mol%, the mol% refer to) phen (1,10 '-Féraud Quinoline), the 7.4mg percentage ratio of DMAP and compound B mole (5mol%, the mol% refer to) DMAP (4-diformazan ammonia Yl pyridines), 166mg (1.2mmol) K2CO3, 2mL glycol dimethyl ether, 1.7mL Isosorbide-5-Nitrae-dioxane, inject 300 uL CH2Isosorbide-5-Nitrae-the dioxane solution (concentration: 2M, 0.6mmol) of FBr, after stirring 24 hours, separates and produces at 70 DEG C Rate is 84%, and purity is identified more than 95% through hydrogen spectrum.1H NMR (400MHz, CDCl3) δ 7.97 (d, J=8.0Hz, 2 H), 7.56 (d, J=7.9Hz, 2H), 5.49 (d, J=46.9Hz, 2H), 3.06 (s, 3H).13C NMR (100MHz, CDCl3) δ 142.3 (d, J=17.5Hz), 140.4 (d, J=2.3Hz), 127.6,127.2 (d, J=6.9Hz), 83.0 (d, J= 170.0Hz), 44.4.19F NMR (376MHz, CDCl3) δ-215.1 (t, J=46.9Hz, 1F) .IR (membrane process) vmax 3078,3000,1601,1411,1305,1146,1010cm-1.MS (EI): m/z (%) 188 (M+), 173,125,109 (100), 83.HRMS:Calculated for (theoretical value) C8H9FO2S:188.0307；Found (measured value): 188.0309.
Embodiment 14
In the reaction tube of 25mL, add 230mg (0.9mmol) 4-(sulphonyl pyrrolin) phenylboric acid, 13.2mg (10 Mol%, mol% refer to NiCl2DME and the percentage ratio of compound B mole) NiCl2DME (dimethyl second two Ether closes Nickel dichloride .), the 10.8mg percentage ratio of phen and compound B mole (10mol%, the mol% refer to) phen (1,10 '-phenanthroline), the 14.4mg percentage ratio of DMAP and compound B mole (10mol%, the mol% refer to) DMAP (DMAP), 166mg (1.2mmol) K2CO3, 2mL glycol dimethyl ether, 1.7mL Isosorbide-5-Nitrae-dioxane, Injection 300uL CH2Isosorbide-5-Nitrae-the dioxane solution (concentration: 2M, 0.6mmol) of FBr, stirs 24 hours at 70 DEG C After, separating productivity is 50%, and purity is identified more than 95% through hydrogen spectrum.1H NMR (400MHz, CDCl3)δ7.86-7.81 (m, 2H), 7.53-7.47 (m, 2H), 5.46 (d, J=47.1Hz, 2H), 3.26-3.20 (m, 4H), 1.78-1.70 (m, 4H).13C NMR (125.7MHz, CDCl3) δ 141.0 (d, J=17.5Hz), 137.1 (d, J=2.1Hz), 127.7,127.1 (d, J=6.7Hz), 83.3 (d, J=169.3Hz), 47.9,25.2.19F NMR (376MHz, CDCl3) δ-213.7 (t, J= 47.1Hz) .IR (membrane process) vmax3097,2886,1460,1334,1164cm-1.MS (EI): m/z (%) 243 (M+), 210, 173,109,83,70 (100) .HRMS:Calculated for (theoretical value) C11H14FNO2S:243.0729；Found (actual measurement Value): 243.0727.
Embodiment 15
In the reaction tube of 25mL, addition 175mg (0.9mmol) 4-halogen trimethylsilylbenzene boric acid, 6.6mg (5mol%, Mol% refers to NiCl2DME and the percentage ratio of compound B mole) NiCl2(dimethyl second diether closes chlorine to DME Change nickel), and the 5.4mg percentage ratio of phen and compound B mole (5mol%, the mol% refer to) phen (1,10 '-Féraud Quinoline), the 7.4mg percentage ratio of DMAP and compound B mole (5mol%, the mol% refer to) DMAP (4-diformazan ammonia Yl pyridines), 166mg (1.2mmol) K2CO3, 2mL glycol dimethyl ether, 1.7mL Isosorbide-5-Nitrae-dioxane, inject 300 uL CH2Isosorbide-5-Nitrae-the dioxane solution (concentration: 2M, 0.6mmol) of FBr, after stirring 24 hours, separates and produces at 70 DEG C Rate is 82%, and purity is identified more than 95% through hydrogen spectrum.1H NMR (400MHz, CDCl3) δ 7.58 (d, J=7.7Hz, 2 H), 7.39 (d, J=7.0Hz, 2H), 5.39 (d, J=47.8Hz, 2H), 0.30 (s, 9H).13C NMR (100MHz, CDCl3) δ 141.3 (d, J=2.5Hz), 136.6 (d, J=17.0Hz), 133.6,126.7 (d, J=5.8Hz), 84.5 (d, J= 166.1Hz) ,-1.2.19F NMR (376MHz, CDCl3) δ-207.7 (t, J=47.8Hz, 1F) .IR (membrane process) vmax 3073,2956,1398,1249,1107,989cm-1.MS (EI): m/z (%) 182 (M+), 167 (100), 137,77.HRMS: Calculated for (theoretical value) C10H15FSi:182.0927；Found (measured value): 182.0930.
Embodiment 16
In the reaction tube of 25mL, addition 172mg (0.9mmol) 3,4-dichloro-benzenes boric acid, 13.2mg (10mol%, Mol% refers to NiCl2DME and the percentage ratio of compound B mole) NiCl2(dimethyl second diether closes chlorine to DME Change nickel), the 10.8mg percentage ratio of phen and compound B mole (10mol%, the mol% refer to) phen (1,10 '-phenanthrene Sieve quinoline), the 14.4mg percentage ratio of DMAP and compound B mole (10mol%, the mol% refer to) DMAP (4-bis- Methylamino pyridine), 166mg (1.2mmol) K2CO3, 2mL glycol dimethyl ether, 1.7mL Isosorbide-5-Nitrae-dioxane, note Penetrate 300uL CH2Isosorbide-5-Nitrae-the dioxane solution (concentration: 2M, 0.6mmol) of FBr, after stirring 24 hours at 70 DEG C, Separating productivity is 50%, and purity is identified more than 95% through hydrogen spectrum.1H NMR (400MHz, CDCl3) δ 7.49-7.43 (m, 2H), 7.20 (d, J=8.3Hz, 1H), 5.33 (d, J=47.3Hz, 2H).13C NMR (125.7MHz, CDCl3)δ136.3 (d, J=18.0Hz), 132.8 (d, J=2.8Hz), 132.7,130.6,129.1 (d, J=6.7Hz), 126.3 (d, J=6.2Hz), 82.9 (d, J=169.2Hz).19F NMR (376MHz, CDCl3) δ-210.1 (t, J=47.3Hz, 1F).
Embodiment 17
In the reaction tube of 25mL, add 251mg (0.9mmol) 4-((1-naphthoxy) methyl) phenylboric acid, 6.6mg (5mol%, mol% refer to NiCl2DME and the percentage ratio of compound B mole) NiCl2DME (dimethyl second Diether closes Nickel dichloride .), the 5.4mg percentage ratio of phen and compound B mole (5mol%, the mol% refer to) phen (1,10 '-phenanthroline), the 7.4mg percentage ratio of DMAP and compound B mole (5mol%, the mol% refer to) DMAP (DMAP), 166mg (1.2mmol) K2CO3, 2mL glycol dimethyl ether, 1.7mL Isosorbide-5-Nitrae-dioxane, Injection 300uL CH2Isosorbide-5-Nitrae-the dioxane solution (concentration: 2M, 0.6mmol) of FBr, stirs 24 hours at 70 DEG C After, separating productivity is 50%, and purity is identified more than 95% through hydrogen spectrum.1H NMR (400MHz, CDCl3)δ8.43-8.39 (m, 1H), 7.88-7.85 (m, 1H), 7.62-7.57 (m, 2H), 7.57-7.49 (m, 3H), 7.47 (dd, J=8.1Hz, 1.7Hz, 2H), 7.43-7.38 (m, 1H), 6.90 (d, J=7.5Hz, 1H), 5.44 (d, J=47.8Hz, 2H), 5.29 (d, J=1.0Hz, 2H).13C NMR (125.7MHz, CDCl3) δ 154.3,137.7 (d, J=3.0Hz), 135.8 (d, J= 17.0Hz), 134.5,127.7 (d, J=5.8Hz), 127.5,126.4,125.8,125.7,125.2,122.1,120.6,105.2, (84.3 d, J=166.2Hz), 69.6.19F NMR (376MHz, CDCl3) δ-206.7 (t, J=47.9Hz, 1F) .IR is (thin Embrane method) vmax3060,2927,1579,1469,1267,1096cm-1.MS (EI): m/z (%) 266 (M+), 123 (100), 115, 103,77.HRMS:Calculated for (theoretical value) C18H15FO:266.1107；Found (measured value): 266.1105.
Embodiment 18
In the reaction tube of 25mL, adding 155mg (0.9mmol) 2-naphthalene boronic acids, (5mol%, mol% are 6.6mg Refer to NiCl2DME and the percentage ratio of compound B mole) NiCl2DME (dimethyl second diether closes Nickel dichloride .), 5.4 The mg percentage ratio of phen and compound B mole (5mol%, the mol% refer to) phen (1,10 '-phenanthroline), 7.4mg The percentage ratio of DMAP and compound B mole (5mol%, the mol% refer to) DMAP (DMAP), 166 mg(1.2mmol)K2CO3, 2mL glycol dimethyl ether, 1.7mL Isosorbide-5-Nitrae-dioxane, inject 300uL CH2FBr's Isosorbide-5-Nitrae-dioxane solution (concentration: 2M, 0.6mmol), after stirring 24 hours at 70 DEG C, separating productivity is 64%, pure Spend and identify more than 95% through hydrogen spectrum.1H NMR (400MHz, CDCl3) δ 7.90-7.83 (m, 4H), 7.54-7.47 (m, 3H), 5.55 (d, J=47.7Hz, 2H).19F NMR (376MHz, CDCl3) δ-206.6 (t, J=47.8Hz, 1F).
Embodiment 19
In the reaction tube of 25mL, addition 214mg (0.9mmol) 9,9-dimethyl fluorene-2-boric acid, 6.6mg (5mol%, Mol% refers to NiCl2DME and the percentage ratio of compound B mole) NiCl2(dimethyl second diether closes chlorine to DME Change nickel), and the 5.4mg percentage ratio of phen and compound B mole (5mol%, the mol% refer to) phen (1,10 '-Féraud Quinoline), the 7.4mg percentage ratio of DMAP and compound B mole (5mol%, the mol% refer to) DMAP (4-diformazan ammonia Yl pyridines), 166mg (1.2mmol) K2CO3, 2mL glycol dimethyl ether, 1.7mL Isosorbide-5-Nitrae-dioxane, inject 300 uL CH2Isosorbide-5-Nitrae-the dioxane solution (concentration: 2M, 0.6mmol) of FBr, after stirring 24 hours, separates and produces at 70 DEG C Rate is 50%, and purity is identified more than 95% through hydrogen spectrum.1H NMR (400MHz, CDCl3) δ 7.78-7.72 (m, 2H), 7.49-7.44 (m, 2H), 7.38-7.34 (m, 3H), 5.46 (d, J=48.1Hz, 2H), 1.52 (s, 6H).13C NMR (125.7MHz, CDCl3) δ 154.0 (d, J=1.7Hz), 153.8,139.9 (d, J=3.4Hz), 138.6 (d, J=1.6Hz), 135.0 (d, J=16.4Hz), 127.6,127.0,126.8 (d, J=5.7Hz), 122.6,122.2 (d, J=5.7Hz), 120.2, 120.0 (d, J=1.5Hz), 85.1 (d, J=165.9Hz), 46.9,27.1.19F NMR (376MHz, CDCl3)δ-203.4 (t, J=48.1Hz, 1F) .IR (membrane process) vmax2960,2923,1472,1449,1216,977cm-1.MS (EI): m/z (%) 226(M+), 211 (100), 191,178,98.HRMS:Calculated for (theoretical value) C13H10F2: 226.1158；Found (measured value): 226.1154.
Embodiment 20
In the reaction tube of 25mL, addition 191mg (0.9mmol) dibenzofurans-4-boric acid, 6.6mg (5mol%, Mol% refers to NiCl2DME and the percentage ratio of compound B mole) NiCl2(dimethyl second diether closes chlorine to DME Change nickel), and the 5.4mg percentage ratio of phen and compound B mole (5mol%, the mol% refer to) phen (1,10 '-Féraud Quinoline), the 7.4mg percentage ratio of DMAP and compound B mole (5mol%, the mol% refer to) DMAP (4-diformazan ammonia Yl pyridines), 166mg (1.2mmol) K2CO3, 2mL glycol dimethyl ether, 1.7mL Isosorbide-5-Nitrae-dioxane, inject 300 uL CH2Isosorbide-5-Nitrae-the dioxane solution (concentration: 2M, 0.6mmol) of FBr, after stirring 24 hours, separates and produces at 70 DEG C Rate is 75%, and purity is identified more than 95% through hydrogen spectrum.1H NMR (400MHz, CDCl3) δ 7.96 (d, J=7.7Hz, 2 H), 7.62 (d, J=8.3Hz, 1H), 7.55-7.46 (m, 2H), 7.41-7.35 (m, 2H), 5.81 (d, J=47.8Hz, 2 H).13C NMR (125.7MHz, CDCl3) δ 156.1,153.9 (d, J=3.8Hz), 127.4,126.9 (d, J=6.1Hz), 124.5 (d, J=1.2Hz), 123.9,122.9,122.7 (d, J=1.8Hz), 121.4 (d, J=3.1Hz), 120.7,120.1 (d, J=17.9Hz), 111.8,79.6 (d, J=165.9Hz).19F NMR (376MHz, CDCl3) δ-210.6 (t, J=47.7 Hz, 1F).
Embodiment 21
In the reaction tube of 25mL, addition 193mg (0.9mmol) 4-phenoxy group phenylboric acid, 13.2mg (10mol%, Mol% refers to NiCl2DME and the percentage ratio of compound B mole) NiCl2(dimethyl second diether closes chlorine to DME Change nickel), the 10.8mg percentage ratio of phen and compound B mole (10mol%, the mol% refer to) phen (1,10 '-phenanthrene Sieve quinoline), the 14.4mg percentage ratio of DMAP and compound B mole (10mol%, the mol% refer to) DMAP (4-bis- Methylamino pyridine), 166mg (1.2mmol) K2CO3, 2mL glycol dimethyl ether, 1.7mL Isosorbide-5-Nitrae-dioxane, note Penetrate 300uL CH2Isosorbide-5-Nitrae-the dioxane solution (concentration: 2M, 0.6mmol) of FBr, after stirring 24 hours at 70 DEG C, Fluorine spectrum productivity 61%.19F NMR (376MHz, CDCl3) δ-202.8 (t, J=48.3Hz, 1F) .GC-MS analysis: M/z (%) 202 (M+), 169,141,109 (100), 77,51.
Embodiment 22
In the reaction tube of 25mL, addition 185mg (0.9mmol) 4-trifluoromethoxy phenylboric acid, 6.6mg (5mol%, Mol% refers to NiCl2DME and the percentage ratio of compound B mole) NiCl2(dimethyl second diether closes chlorine to DME Change nickel), and the 5.4mg percentage ratio of phen and compound B mole (5mol%, the mol% refer to) phen (1,10 '-Féraud Quinoline), the 7.4mg percentage ratio of DMAP and compound B mole (5mol%, the mol% refer to) DMAP (4-diformazan ammonia Yl pyridines), 166mg (1.2mmol) K2CO3, 2mL glycol dimethyl ether, 1.7mL Isosorbide-5-Nitrae-dioxane, inject 300 uL CH2Isosorbide-5-Nitrae-the dioxane solution (concentration: 2M, 0.6mmol) of FBr, after stirring 24 hours at 70 DEG C, fluorine spectrum is produced Rate 78%.19F NMR (376MHz, CDCl3) δ-208.7 (t, J=47.5Hz, 1F).
Embodiment 23
In the reaction tube of 25mL, addition 185mg (0.9mmol) 4-trifluoromethoxy phenylboric acid, 6.6mg (5mol%, Mol% refers to NiCl2DME and the percentage ratio of compound B mole) NiCl2(dimethyl second diether closes chlorination to DME Nickel), the 5.4mg percentage ratio of phen and compound B mole (5mol%, the mol% refer to) phen (1,10 '-phenanthroline), The 7.4mg percentage ratio of DMAP and compound B mole (5mol%, the mol% refer to) DMAP (DMAP), 166mg(1.2mmol)K2CO3, 2mL glycol dimethyl ether, 1.7mL Isosorbide-5-Nitrae-dioxane, inject 300uL CH2FBr Isosorbide-5-Nitrae-dioxane solution (concentration: 2M, 0.6mmol), stir after 24 hours at 70 DEG C, fluorine spectrum productivity 90%.19F NMR (376MHz, CDCl3) δ-211.2 (t, J=47.4Hz, 1F).
Embodiment 24
In the reaction tube of 25mL, addition 171mg (0.9mmol) 4-trifluoromethylbenzene boronic acid, 6.6mg (5mol%, Mol% refers to NiCl2DME and the percentage ratio of compound B mole) NiCl2(dimethyl second diether closes chlorination to DME Nickel), the 5.4mg percentage ratio of phen and compound B mole (5mol%, the mol% refer to) phen (1,10 '-phenanthroline), The 7.4mg percentage ratio of DMAP and compound B mole (5mol%, the mol% refer to) DMAP (DMAP), 166mg(1.2mmol)K2CO3, 2mL glycol dimethyl ether, 1.7mL Isosorbide-5-Nitrae-dioxane, inject 300uL CH2FBr Isosorbide-5-Nitrae-dioxane solution (concentration: 2M, 0.6mmol), stir after 24 hours at 70 DEG C, fluorine spectrum productivity 84%.19F NMR (376MHz, CDCl3) δ-213.5 (t, J=47.1Hz, 1F).
Embodiment 25
In the reaction tube of 25mL, add 164mg (0.9mmol) 4-ethyl phenyl sulfide boric acid, 6.6mg (5mol%, mol% Refer to NiCl2DME and the percentage ratio of compound B mole) NiCl2DME (dimethyl second diether closes Nickel dichloride .), 5.4 The mg percentage ratio of phen and compound B mole (5mol%, the mol% refer to) phen (1,10 '-phenanthroline), 7.4mg (5 Mol%, mol% refer to the percentage ratio of DMAP and compound B mole) DMAP (DMAP), 166mg (1.2mmol)K2CO3, 2mL glycol dimethyl ether, 1.7mL Isosorbide-5-Nitrae-dioxane, inject 300uL CH2The Isosorbide-5-Nitrae of FBr- Dioxane solution (concentration: 2M, 0.6mmol), after stirring 24 hours at 70 DEG C, fluorine spectrum productivity 68%.19F NMR (376MHz, CDCl3) δ-205.5 (t, J=48.1Hz, 1F) .GC-MS Found (measured value): m/z (%) 170 (M+), 155,142,135,109 (100), 97,77,51.
Embodiment 26
In the reaction tube of 25mL, add 134mg (0.45mmol) estrone phenylboric acid, 6.6mg (10mol%, mol% Refer to NiCl2DME and the percentage ratio of compound B mole) NiCl2DME (dimethyl second diether closes Nickel dichloride .), The 5.4mg percentage ratio of phen and compound B mole (10mol%, the mol% refer to) phen (1,10 '-phenanthroline), 7.4 The mg percentage ratio of DMAP and compound B mole mole (10mol%, the mol% refer to) DMAP (4-dimethylamino Pyridine), 83mg (1.2mmol) K2CO3, 1mL glycol dimethyl ether, 0.85mL Isosorbide-5-Nitrae-dioxane, inject 150 uL CH2Isosorbide-5-Nitrae-the dioxane solution (concentration: 2M, 0.6mmol) of FBr, after stirring 24 hours, separates and produces at 70 DEG C Rate is 56%, and purity is identified more than 95% through hydrogen spectrum.1H NMR (400MHz, CDCl3) δ 7.33 (d, J=7.9Hz, 1 H), 7.18 (d, J=7.8Hz, 1H), 7.14 (s, 1H), 5.32 (d, J=48.1Hz, 2H), 2.94 (d, J=4.9Hz, 2H), 2.61-2.40 (m, 2H), 2.32 (s, 1H), 2.22-1.94 (m, 4H), 1.73-1.39 (m, 6H), 0.92 (s, 3H).13C NMR (100MHz, CDCl3) δ 220.7,140.4 (d, J=3.0Hz), 136.8,133.5 (d, J=16.9Hz), 128.4 (d, J=5.4Hz), 125.6,125.1 (d, J=5.2Hz), 84.5 (d, J=165.2Hz), 50.4,47.9,44.3,38.0,35.8, 31.5,29.2,26.3,25.6,21.50,13.7.19F NMR (376MHz, CDCl3) δ-204.6 (t, J=48.0Hz, 1F). IR (membrane process) vmax2967,1735,1612,1452,1255,978cm-1.MS (EI): m/z (%) 286 (M+), 253,242, 229,164,107 (100) .HRMS:Calculated for (theoretical value) C19H23FO:286.1733；Found (measured value): 286.1735.
Embodiment 27
In the reaction tube of 25mL, add 184mg (0.45mmol)6.6mg (10mol%, Mol% refers to NiCl2DME and the percentage ratio of compound B mole) NiCl2(dimethyl second diether closes chlorine to DME Change nickel), and the 5.4mg percentage ratio of phen and compound B mole (10mol%, the mol% refer to) phen (1,10 '-Féraud Quinoline), the 7.4mg percentage ratio of DMAP and compound B mole (10mol%, the mol% refer to) DMAP (4-diformazan ammonia Yl pyridines), 83mg (1.2mmol) K2CO3, 1mL glycol dimethyl ether, 0.85mL Isosorbide-5-Nitrae-dioxane, inject 150 uL CH2Isosorbide-5-Nitrae-the dioxane solution (concentration: 2M, 0.6mmol) of FBr, after stirring 24 hours, separates and produces at 70 DEG C Rate is 50%, and purity is identified more than 95% through hydrogen spectrum.1H NMR (400MHz, CDCl3) δ 8.05 (d, J=7.9Hz, 2 H), 7.45 (d, J=7.6Hz, 2H), 5.96 (d, J=3.6Hz, 1H), 5.51 (d, J=2.7Hz, 1H), 5.46 (d, J= 47.2Hz, 2H) 4.64 (d, J=3.7Hz, 1H), 4.37-4.30 (m, 2H), 4.14-4.05 (m, 2H), 1.56 (s, 3H), (1.41 s, 3H), 1.32 (s, 2H), 1.26 (s, 3H).13C NMR (125.7MHz, CDCl3) δ 164.7,141.8 (d, J= 17.3Hz), 130.0,129.6 (d, J=2.1Hz), 126.6 (d, J=6.7Hz), 112.4,109.4,105.1,83.5 (d, J= 169.1Hz), 83.4,80.0,76.7,72.5,67.3,26.8,26.7,26.2,25.2.19F NMR (376MHz, CDCl3)δ- 213.6 (t, J=47.1Hz, 1F) .IR (membrane process) vmax cm-12990,2940,1729,1617,1386,1016cm-1.MS (ESI): m/z (%) 419 (M+Na)+, 339 (100), 299,274,167.HRMS (ESI): Calculated for (theoretical value) C20H25FNaO7: 419.1482；Found (measured value): 419.1477.
Embodiment 28
In the reaction tube of 25mL, add 184mg (0.45mmol) 4-(sulphonyl-2-carbethoxyl group piperidines) phenylboric acid, (10mol%, mol% refer to NiCl to 6.6mg2DME and the percentage ratio of compound B mole) NiCl2DME (two Methyl second diether closes Nickel dichloride .), the 5.4mg percentage ratio of phen and compound B mole (10mol%, the mol% refer to) Phen (1,10 '-phenanthroline), the 7.4mg percentage ratio of DMAP and compound B mole (10mol%, the mol% refer to) DMAP (DMAP), 83mg (1.2mmol) K2CO3, 1mL glycol dimethyl ether, 0.85mL Isosorbide-5-Nitrae-two Oxygen six ring, injects 150uL CH2Isosorbide-5-Nitrae-the dioxane solution (concentration: 2M, 0.6mmol) of FBr, stirs at 70 DEG C After 24 hours, separating productivity is 50%, and purity is identified more than 95% through hydrogen spectrum.1H NMR (400MHz, CDCl3)δ 7.79 (d, J=8.2Hz, 2H), 7.45 (d, J=8.0Hz, 2H), 5.43 (d, J=47.1Hz, 2H), 4.72 (d, J=5.1 Hz, 1H), 4.04-3.90 (m, 2H), 3.76 (d, J=10.1Hz, 1H), 3.24-3.15 (m, 1H), 2.12 (d, J=14.2 Hz, 1H), 1.77-1.60 (m, 3H), 1.54-1.40 (m, 1H), 1.30-1.20 (m, 1H), 1.12 (t, J=7.1Hz, 3 H).13C NMR (100MHz, CDCl3) δ 170.5,140.7 (d, J=17.5Hz), 140.0 (d, J=2.4Hz), 127.4, 126.8 (d, J=6.7Hz), 83.2 (d, J=169.3Hz), 61.0,55.0,42.6,27.8,24.6,19.9,14.0.19F NMR (376MHz, CDCl3) δ-213.7 (t, J=47.1Hz, 1F) .IR (membrane process) vmax cm-12974,2888,1743,1381, 1159,1050cm-1.MS (MALDI): m/z (%) 347 (M+NH4)+(100), 330 (M+H)+.HRMS (MALDI): Calculated for (theoretical value) C15H21O4NFS:330.1170.Found (measured value) (M+H)+: 330.1169.
Embodiment 29
In the reaction tube of 25mL, add 74.9mg (0.6mmol) DMAP (DMAP), 2mL second two Diethylene glycol dimethyl ether, 1.7mL Isosorbide-5-Nitrae-dioxane, inject 300uL CH2Isosorbide-5-Nitrae-the dioxane solution of FBr (concentration: 2M, 0.6mmol), after being stirred at room temperature 8 hours, separating productivity is 82%, and purity is identified more than 95% through hydrogen spectrum.1H NMR (400MHz, DMSO-d6) δ 8.51 (d, J=7.9Hz, 2H), 7.16 (d, J=7.8Hz, 2H), 6.19 (d, J=50.4Hz, 2H), 3.26 (s, 6H).13C NMR (125.7MHz, DMSO-d6) δ 156.8,142.2 (d, J=1.2Hz), 107.8,92.1 (d, J=202.1Hz), 40.3.19F NMR (376MHz, DMSO-d6) δ-164.6 (t, J=50.4Hz, 1F) .MS (ESI): M/z (%) 155.9,155.0 (M-79Br, 100)+.
Embodiment 30
In the reaction tube of 25mL, add 66mg (0.45mmol) 4-cyanophenylboronic acid, 3.3mg (5mol%, mol% Refer to NiCl2DME and the percentage ratio of compound B mole) NiCl2DME (dimethyl second diether closes Nickel dichloride .), 2.7 The mg percentage ratio of phen and compound B mole (5mol%, the mol% refer to) phen (1,10 '-phenanthroline), 3.7mg (5 Mol%, mol% refer to the percentage ratio of DMAP and compound B mole) DMAP (DMAP), 83mg (1.2 mmol)K2CO3, 1mL glycol dimethyl ether, 0.85mL Isosorbide-5-Nitrae-dioxane, inject 150uL's Isosorbide-5-Nitrae-dioxane solution (concentration: 2M, 0.3mmol), after stirring 24 hours at 70 DEG C, separating productivity is 57%.1H NMR (400MHz, CDCl3) δ 7.62 (d, J=8.1Hz, 1H), 7.33 (d, J=8.2Hz, 1H), 7.30-7.21 (m, 1H), 7.10 (d, J=6.3Hz, 1H), 5.68 (ddd, J=47.1,7.2,5.4Hz, 1H), 3.17 (dddd, J=31.0,19.5, 14.2,6.3Hz, 1H).13C NMR (125.7MHz, CDCl3) δ 144.8 (d, J=20.5Hz), 135.3 (d, J=4.5Hz), 132.2,129.5,128.5,127.0,126.1 (d, J=7.3Hz), 118.5,112.1 (d, J=1.5Hz), 93.7 (d, J=177.4 Hz), 43.7 (d, J=23.7Hz).19F NMR (376MHz, CDCl3) δ-177.9 (ddd, J=47.0,25.6,19.2Hz, 1F).
Embodiment 31
In the reaction tube of 25mL, addition 87mg (0.45mmol) 4-carbethoxyl group phenylboric acid, 3.3mg (5mol%, Mol% refers to NiCl2DME and the percentage ratio of compound B mole) NiCl2(dimethyl second diether closes chlorine to DME Change nickel), and the 2.7mg percentage ratio of phen and compound B mole (5mol%, the mol% refer to) phen (1,10 '-Féraud Quinoline), the 3.7mg percentage ratio of DMAP and compound B mole (5mol%, the mol% refer to) DMAP (4-diformazan ammonia Yl pyridines), 83mg (1.2mmol) K2CO3, 1mL glycol dimethyl ether, 0.85mL Isosorbide-5-Nitrae-dioxane, inject 150 uLIsosorbide-5-Nitrae-dioxane solution (concentration: 2M, 0.3mmol), stir after 24 hours at 70 DEG C, Separating productivity is 70%.1HNMR (500MHz, CDCl3) δ 8.05 (d, J=8.0Hz, 2H), 7.34 (d, J=8.4Hz, 2H), 7.32-7.25 (m, 3H), 7.16 (d, J=6.9Hz, 2H), 5.70 (ddd, J=47.2,7.6,5.2Hz, 1H), 4.41 (q, J=7.1Hz, 2H), 3.21 (dddd, J=26.6,19.4,14.2,6.4Hz, 2H), 1.42 (t, J=7.1Hz, 3H).13C NMR (125.7MHz, CDCl3) δ 166.2,144.5 (d, J=20.0Hz), 135.9 (d, J=4.3Hz), 130.3 (d, J= 1.5Hz), 129.6,129.5,128.4,126.80,125.4 (d, J=7.1Hz), 94.2 (d, J=176.0Hz), 61.0,43.8 (d, J=23.9Hz), 14.3.19F NMR (376MHz, CDCl3) δ-176.4 (ddd, J=47.4,26.7,18.6Hz, 1F) .IR (membrane process) vmax3086,1941,1713,1614,1472,1280,1042cm-1.MS (EI): m/z (%) 272 (M+), 227, 181,91 (100) .HRMS:Calculated for (theoretical value) C17H17FO2: 272.1213；Found (measured value): 272.1213.
Embodiment 32
In the reaction tube of 25mL, addition 74mg (0.45mmol) 4-acetylbenzene boric acid, 3.3mg (5mol%, Mol% refers to NiCl2DME and the percentage ratio of compound B mole) NiCl2(dimethyl second diether closes chlorine to DME Change nickel), and the 2.7mg percentage ratio of phen and compound B mole (5mol%, the mol% refer to) phen (1,10 '-Féraud Quinoline), the 3.7mg percentage ratio of DMAP and compound B mole (5mol%, the mol% refer to) DMAP (4-diformazan ammonia Yl pyridines), 83mg (1.2mmol) K2CO3, 1mL glycol dimethyl ether, 0.85mL Isosorbide-5-Nitrae-dioxane, inject 150 uLIsosorbide-5-Nitrae-dioxane solution (concentration: 2M, 0.3mmol), stir after 24 hours at 70 DEG C, Separating productivity is 60%.1H NMR (500MHz, CDCl3) δ 7.96 (d, J=8.0Hz, 2H), 7.39 (d, J=8.3Hz, 2H), 7.29 (t, J=7.4Hz, 2H), 7.20 (d, J=7.4Hz, 1H), 7.17 (dd, J=7.5,0.5Hz, 2H), 5.52 (ddd, J=11.7,7.9,4.2Hz, 1H), 2.68 (t, J=7.4Hz, 2H), 2.61 (s, 3H), 2.01-1.72 (m, 4H).13C NMR (125.7MHz, CDCl3) δ 197.5,145.5 (d, J=19.9Hz), 141.6,136.8 (d, J=1.3Hz), 128.5, 128.3 (d, J=0.6Hz), 125.9,125.4,125.33,93.7 (d, J=172.7Hz), 36.6 (d, J=23.1Hz), 35.4, 26.6,26.5 (d, J=3.9Hz).19F NMR (376MHz, CDCl3) δ-178.9 (ddd, J=48.1,28.2,18.8Hz, 1 F) .MS (EI): m/z (%) 271 (M+1) 270 (M+), 255,207,165,104,91 (100), 77,43.HRMS: Calculated for (theoretical value) C18H19FO:270.1420；Found (measured value): 270.1425.
Embodiment 33
In the reaction tube of 25mL, addition 86mg (0.45mmol) 4-trifluoromethylbenzene boronic acid, 3.3mg (5mol%, Mol% refers to NiCl2DME and the percentage ratio of compound B mole) NiCl2(dimethyl second diether closes chlorine to DME Change nickel), and the 2.7mg percentage ratio of phen and compound B mole (5mol%, the mol% refer to) phen (1,10 '-Féraud Quinoline), the 3.7mg percentage ratio of DMAP and compound B mole (5mol%, the mol% refer to) DMAP (4-diformazan ammonia Yl pyridines), 83mg (1.2mmol) K2CO3, 1mL glycol dimethyl ether, 0.85mL Isosorbide-5-Nitrae-dioxane, inject 150 uLIsosorbide-5-Nitrae-dioxane solution (concentration: 2M, 0.3mmol), at 70 DEG C stir 24 hours After, separating productivity is 70%.1H NMR (500MHz, CDCl3) δ 7.64 (d, J=8.1Hz, 2H), 7.42 (d, J= 8.0Hz, 2H), 7.31 (t, J=7.5Hz, 2H), 7.22 (d, J=7.4Hz, 1H), 7.19 (d, J=7.1Hz, 2H), 5.52 (ddd, J=47.4,7.9,3.9Hz, 1H), 2.70 (t, J=7.4Hz, 2H), 2.02-1.74 (m, 4H).19F NMR(376 MHz, CDCl3) δ-62.6 (s, 3F) ,-178.8 (ddd, J=47.8,28.6,18.8Hz, 1F) .IR (membrane process) vmax3030, 1931,1621,1463,1325,1066cm-1.MS (EI): m/z (%) 269 (M+), 277,177,127,104,91 (100), 65.HRMS:Calculated for (theoretical value) C17H16F4: 296.1188；Found (measured value): 296.1190.
Embodiment 34
In the reaction tube of 25mL, addition 68mg (0.45mmol) 4-formylphenylboronic acid, 3.3mg (5mol%, Mol% refers to NiCl2DME and the percentage ratio of compound B mole) NiCl2(dimethyl second diether closes chlorine to DME Change nickel), and the 2.7mg percentage ratio of phen and compound B mole (5mol%, the mol% refer to) phen (1,10 '-Féraud Quinoline), the 3.7mg percentage ratio of DMAP and compound B mole (5mol%, the mol% refer to) DMAP (4-diformazan ammonia Yl pyridines), 83mg (1.2mmol) K2CO3, 1mL glycol dimethyl ether, 0.85mL Isosorbide-5-Nitrae-dioxane, inject 150 uLIsosorbide-5-Nitrae-dioxane solution (concentration: 2M, 0.3mmol), at 70 DEG C stir 24 After hour, separating productivity is 85%.1H NMR (500MHz, CDCl3) δ 10.01 (s, 1H), 7.88 (d, J=8.1Hz, 2H), 7.47 (d, J=8.0Hz, 2H), 5.50 (ddd, J=47.9,8.0,4.7Hz, 1H), 1.96-1.75 (m, 2H), 1.42 -1.19 (m, 12H), 0.87 (t, J=6.8Hz, 3H).13C NMR (125.7MHz, CDCl3) δ 191.7,147.3 (d, J= 19.9Hz), 136.0 (d, J=1.2Hz), 129.8,125.8 (d, J=7.6Hz), 93.8 (d, J=172.9Hz), 37.2 (d, J= 23.0Hz), 31.8,29.34,29.3,29.1,24.8 (d, J=4.0Hz), 22.6,14.0.19F NMR (376MHz, CDCl3) δ-179.3 (ddd, J=48.1,29.0,18.4Hz, 1F) .IR (membrane process) vmax3389,2926,1705,1612,1466, 1210,1065cm-1.MS (EI): m/z (%) 250 (M+), 138 (100), 132,109,91,71,57,43.HRMS: Calculated for (theoretical value) C16H23FO:250.1733；Found (measured value): 250.1734.
Embodiment 35
In the reaction tube of 25mL, add 66mg (0.45mmol) 4-cyanophenylboronic acid, 3.3mg (5mol%, mol% Refer to NiCl2DME and the percentage ratio of compound B mole) NiCl2DME (dimethyl second diether closes Nickel dichloride .), The 2.7mg percentage ratio of phen and compound B mole (5mol%, the mol% refer to) phen (1,10 '-phenanthroline), 3.7 The mg percentage ratio of DMAP and compound B mole (5mol%, the mol% refer to) DMAP (DMAP), 83mg(1.2mmol)K2CO3, 1mL glycol dimethyl ether, 0.85mL Isosorbide-5-Nitrae-dioxane, inject 150uLIsosorbide-5-Nitrae-dioxane solution (concentration: 2M, 0.3mmol), at 70 DEG C stir 24 hours After, separating productivity is 81%.1HNMR.1HNMR (500MHz, CDCl3) δ 7.66 (d, J=8.1Hz, 2H), 7.42 (d, J=8.4Hz, 2H), 5.47 (ddd, J=47.8,8.0,4.6Hz, 1H), 1.93-1.74 (m, 2H), 1.44-1.13 (m, 12H), 0.87 (t, J=7.0Hz, 3H).13C NMR (125.7MHz, CDCl3) δ 145.9 (d, J=20.3Hz), 132.2, 125.9 (d, J=7.7Hz), 118.6,111.9 (d, J=1.6Hz), 93.4 (d, J=173.6Hz), 37.2 (d, J=22.9Hz), 31.8,29.33,29.2,29.1,24.8 (d, J=4.0Hz), 22.6,14.0.19F NMR (376MHz, CDCl3)δ-180.0 (ddd, J=47.8,30.0,18.8Hz, 1F) .IR (membrane process) vmax cm-12927,2856,2230,1612,1466,1061. MS (EI): m/z (%) 247 (M+), 135 (100), 129,107,71,57.HRMS:Calculated for (theoretical value) C16H22NF:247.1736；Found (measured value): 247.1735.
Embodiment 36
In the reaction tube of 25mL, add 89mg (0.45mmol) 4-biphenylboronic acid, 3.3mg (5mol%, mol% Refer to NiCl2DME and the percentage ratio of compound B mole) NiCl2DME (dimethyl second diether closes Nickel dichloride .), The 2.7mg percentage ratio of phen and compound B mole (5mol%, the mol% refer to) phen (1,10 '-phenanthroline), 3.7 The mg percentage ratio of DMAP and compound B mole (5mol%, the mol% refer to) DMAP (DMAP), 83mg(1.2mmol)K2CO3, 1mL glycol dimethyl ether, 0.85mL Isosorbide-5-Nitrae-dioxane, inject 150uLIsosorbide-5-Nitrae-dioxane solution (concentration: 2M, 0.3mmol), stir after 24 hours at 70 DEG C, fluorine is composed Productivity is 50%.
Embodiment 37-50
In the reaction tube of 25mL, add 4-biphenylboronic acid (0.45mmol), nickel salt, part, alkali, additive, Solvent (2mL), injects 150uL CH2Isosorbide-5-Nitrae-the dioxane solution (concentration: 2M, 0.6mmol) of FBr, stirs at 70 DEG C Reaction is terminated after mixing 12 hours.
The respective reaction condition of embodiment 37-48 and product fluorine spectrum yield are as shown in table 1, and it is white for obtaining target compound Color solid；It is that interior target fluorine composes yield that described fluorine spectrum yield refers to fluorobenzene.
Table 1
Embodiment 51-79
In the reaction tube of 25mL, add 4-biphenylboronic acid (0.45mmol), nickel salt, part, alkali, additive, Solvent (2mL), injects 150uL CH2Isosorbide-5-Nitrae-the dioxane solution (concentration: 2M, 0.6mmol) of FBr, stirs at 70 DEG C Reaction is terminated after mixing 12 hours.
The respective reaction condition of embodiment 51-79 and product yield are as shown in table 2, obtain target compound solid for white Body.
Table 2
Embodiment 80-81
In the reaction tube of 25mL, add 4-biphenylboronic acid (0.45mmol), nickel salt, part, alkali, additive, Solvent (2mL), injects 150uL CH2Isosorbide-5-Nitrae-the dioxane solution (concentration: 2M, 0.6mmol) of FBr, stirs at 70 DEG C Reaction is terminated after mixing 24 hours.
The respective reaction condition of embodiment 80-81 and product yield are as shown in table 3, obtain target compound solid for white Body.
Table 3
The all documents mentioned in the present invention are incorporated as reference the most in this application, just as each document coverlet Solely it is incorporated as with reference to like that.In addition, it is to be understood that after the above-mentioned teachings having read the present invention, this area skill The present invention can be made various changes or modifications by art personnel, and these equivalent form of values fall within right appended by the application equally and want Seek book limited range.

Claims (14)

1. the preparation method of the compound containing a fluoroalkyl, it is characterised in that it comprises the following steps: in a solvent, Under conditions of alkali, additive, part and catalyst exist, compound A and compound B is carried out suzuki coupling Reaction, obtains compound C, and described catalyst is nickel salt, and described nickel salt is NiLnCl2、NiLnBr2、 NiLnI2Or NiQ2·mH2O；
Wherein, Q is nitrate anion, acetate, acetylacetone,2,4-pentanedione root, chlorine, bromine or iodine, and 0≤m≤10；And 0≤n ＜ 3；L For triphenylphosphine, O-methoxy triphenylphosphine, adjacent methyl triphenyl phosphine, tri-butyl phosphine, tricyclohexyl phosphine, three diamantane (obsolete) Base phosphine, 1,2 pairs of (diphenylphosphine) ethane, 1, double (diphenylphosphine) propane of 3-, Isosorbide-5-Nitrae-bis-(diphenylphosphine) butane, 1,1 '-bis-(two Phenylphosphine) ferrocene, double diphenylphosphine methane, 1, the double two triphenylphosphine benzene of 2-, dimethyl second diether, diethylene glycol dimethyl ether, " substituted or unsubstituted 1,10-phenanthrene quinoline ", " substituted or unsubstituted pyridine ", substituted or unsubstituted bipyridyl or PersonDescribed " substituted or unsubstituted bipyridyl ", " substituted or unsubstituted 1,10-phenanthrene quinoline " or " replacement " described in " replacing or substituted pyridine " refers in heteroatomic non-ortho by C1～C10Alkyl, C1~ C10Alkoxyl andIn one or more replaced, when there is multiple substituent group, described replacement Base is identical or different；X is halogen；R8、R9、R10And R11It is respectively hydrogen or C1～C3Alkyl；R12And R13 It is respectively hydrogen, C1～C3Alkyl, C5～C10Aryl or R12、R13And carbon atom that they are connected is common Form 4-6 membered cyclic structure；R1For " substituted or unsubstituted C3～C15Aryl ", " hetero atom be oxygen, sulfur or Nitrogen-atoms, hetero atom number is 1-3, substituted or unsubstituted C2～C15Heteroaryl " orDescribed " substituted or unsubstituted C3～C15Aryl " or " hetero atom be oxygen, sulfur or Nitrogen-atoms, hetero atom number is 1-3, substituted or unsubstituted C2～C15Heteroaryl " described in " replacement " be By cyano group, halogen, C1～C10Alkyl, C1～C10Alkoxyl, C5～C10Aryloxy group, C1～C10Alkane Sulfenyl, C1～C10Alkyl silyl, " the C of halogen substiuted1～C10Alkyl ", " C of halogen substiuted1～C10's Alkoxyl ", C3～C10Aryl,In one Individual or multiple replaced, when there is multiple substituent group, described substituent group is identical or different；Wherein, R3、R4、R6With R7It is respectively hydrogen atom or C1～C6Alkyl；R5For hydrogen atom, C1～C6Alkyl or " hetero atom be nitrogen-atoms, Hetero atom number is the C of 1-23～C6Heterocyclylalkyl "；R2For H or substituted or unsubstituted C1～C10Alkane Base；Described " substituted or unsubstituted C1～C10Alkyl " described in replacement refer to by C5～C10Aryl Replaced.
2. the preparation method of the compound containing a fluoroalkyl as claimed in claim 1, it is characterised in that:
Described m is 0,1,2,3,4,5,6,7,8,9 or 10；
And/or,
Described n is 0,1,2 or 3；
When described L is " substituted or unsubstituted 1,10-phenanthrene quinoline ", described " unsubstituted 1,10-phenanthrene quinoline " For
And/or,
When " the substituted or unsubstituted bipyridyl " described in described L, " substituted or unsubstituted 1,10-phenanthrene quinoline " or " replacement " described in " replacing or substituted pyridine " refers in heteroatomic non-ortho by C1～C10Alkyl replaced Time, described " C1～C10Alkyl " be C1～C6Alkyl；
And/or,
When " the substituted or unsubstituted bipyridyl " described in described L, " substituted or unsubstituted 1,10-phenanthrene quinoline " or " replacement " described in " replacing or substituted pyridine " refers in heteroatomic non-ortho by C1～C10Alkoxyl taken Dai Shi, described " C1～C10Alkoxyl " be C1～C6Alkoxyl；
And/or,
When described X is halogen, described halogen is chlorine, bromine or iodine；
And/or,
As described R8、R9、R10And R11It is respectively C1～C3Alkyl time, described " C1～C3Alkyl " For methyl, ethyl, propyl group or isopropyl；
And/or,
As described R12And R13It is respectively C1～C3Alkyl time, described " C1～C3Alkyl " be methyl, Ethyl, propyl group or isopropyl；
And/or,
As described R12And R13It is respectively C5～C10Aryl time, described " C5～C10Aryl " be phenyl；
And/or,
As described R12、R13And they carbon atoms of being connected are when being collectively forming 4-6 membered cyclic structure, described Six-membered cyclic structure is
And/or,
As described R1Described in " substituted or unsubstituted C3～C15Aryl " or " hetero atom is oxygen, sulfur or nitrogen Atom, hetero atom number is 1-3, substituted or unsubstituted C2～C15Heteroaryl " described in " replacement " be quilt When halogen is replaced, described " halogen " is fluorine, chlorine, bromine or iodine；
And/or,
As described R1Described in " substituted or unsubstituted C3～C15Aryl " or " hetero atom is oxygen, sulfur or nitrogen Atom, hetero atom number is 1-3, substituted or unsubstituted C2～C15Heteroaryl " described in " replacement " be quilt C1～C10Alkyl replaced time, described " C1～C10Alkyl " be C1～C6Alkyl；
And/or,
As described R1Described in " substituted or unsubstituted C3～C15Aryl " or " hetero atom is oxygen, sulfur or nitrogen Atom, hetero atom number is 1-3, substituted or unsubstituted C2～C15Heteroaryl " described in " replacement " be quilt C1～C10Alkoxyl replaced time, described " C1～C10Alkoxyl " be C1～C6Alkoxyl；
And/or,
As described R1Described in " substituted or unsubstituted C3～C15Aryl " or " hetero atom is oxygen, sulfur or nitrogen Atom, hetero atom number is 1-3, substituted or unsubstituted C2～C15Heteroaryl " described in " replacement " be quilt C5～C10Aryloxy group replaced time, described " C5～C10Aryloxy group " be C5～C6Aryloxy group；
And/or,
As described R1Described in " substituted or unsubstituted C3～C15Aryl " or " hetero atom is oxygen, sulfur or nitrogen Atom, hetero atom number is 1-3, substituted or unsubstituted C2～C15Heteroaryl " described in " replacement " be quilt C1～C10Alkylthio group replaced time, described " C1～C10Alkylthio group " be C1～C6Alkylthio group；
And/or,
As described R1Described in " substituted or unsubstituted C3～C15Aryl " or " hetero atom is oxygen, sulfur or nitrogen Atom, hetero atom number is 1-3, substituted or unsubstituted C2～C15Heteroaryl " described in " replacement " be quilt C1～C10Alkyl silyl replaced time, described " C1～C10Alkyl silyl " be C1～C6Alkyl silyl；
And/or,
As described R1Described in " substituted or unsubstituted C3～C15Aryl " or " hetero atom is oxygen, sulfur or nitrogen Atom, hetero atom number is 1-3, substituted or unsubstituted C2～C15Heteroaryl " described in " replacement " be quilt The C of halogen substiuted1～C10Alkyl replaced time, the described " C of halogen substiuted1～C10Alkyl " be " fluorine, chlorine With the one or more substituted C in bromine atoms1～C6Alkyl "；
And/or,
As described R1Described in " substituted or unsubstituted C3～C15Aryl " or " hetero atom is oxygen, sulfur or nitrogen Atom, hetero atom number is 1-3, substituted or unsubstituted C2～C15Heteroaryl " described in " replacement " be quilt The C of halogen substiuted1～C10Alkoxyl replaced time, the described " C of halogen substiuted1～C10Alkoxyl " be " fluorine, One or more substituted C in chlorine and bromine atoms1～C6Alkoxyl "；
And/or,
As described R1Described in " substituted or unsubstituted C3～C15Aryl " or " hetero atom is oxygen, sulfur or nitrogen Atom, hetero atom number is 1-3, substituted or unsubstituted C2～C15Heteroaryl " described in " replacement " be quilt C3～C10Aryl replaced time, described " C3～C10Aryl " be C3～C6Aryl；
And/or,
As described R3、R4、R6And R7It is respectively C1～C6Alkyl time, described " C1～C6Alkyl " be Methyl, ethyl, propyl group, isopropyl, butyl, isobutyl group or the tert-butyl group；
And/or,
As described R5For C1～C6Alkyl time, described " C1～C6Alkyl " be methyl, ethyl, propyl group, Isopropyl, butyl, isobutyl group or the tert-butyl group；
And/or,
As described R5For " hetero atom be nitrogen-atoms, hetero atom number be the C of 1-23～C6Heterocyclylalkyl " time, Described " hetero atom be nitrogen-atoms, hetero atom number be the C of 1-23～C6Heterocyclylalkyl " be that " hetero atom is that nitrogen is former Son, hetero atom number are the C of 13～C4Heterocyclylalkyl "；
And/or,
As described R2For substituted or unsubstituted C1～C10Alkyl time, described " unsubstituted C1～C10's Alkyl " it is methyl, ethyl, propyl group, butyl, amyl group, hexyl, heptyl, nonyl or decyl；
And/or,
As described R2For substituted or unsubstituted C1～C10Alkyl time, described " substituted C1～C10Alkane Base " the most substituted methyl, substituted ethyl, substituted propyl group, substituted butyl, substituted amyl group, substituted Hexyl, substituted heptyl, substituted nonyl or substituted decyl；
And/or,
As described R2For substituted or unsubstituted C1～C10Alkyl and described " substituted or unsubstituted C1～C10 Alkyl " described in replacement refer to by C5～C10Aryl replaced time, described " C5～C10Aryl " For phenyl.
3. the preparation method of the compound containing a fluoroalkyl as claimed in claim 2, it is characterised in that:
When " the substituted or unsubstituted bipyridyl " described in described L, " substituted or unsubstituted 1,10-phenanthrene quinoline " or " replacement " described in " replacing or substituted pyridine " refers in heteroatomic non-ortho by C1～C6Alkyl replaced Time, described C1～C6Alkyl be methyl, ethyl, propyl group, isopropyl, butyl, isobutyl group or the tert-butyl group；
And/or,
When " the substituted or unsubstituted bipyridyl " described in described L, " substituted or unsubstituted 1,10-phenanthrene quinoline " or " replacement " described in " replacing or substituted pyridine " refers in heteroatomic non-ortho by C1～C6Alkoxyl taken Dai Shi, described C1～C6Alkoxyl be methoxyl group, ethyoxyl, propoxyl group, isopropoxy, butoxy, different Butoxy or tert-butoxy；
And/or,
When described L isTime, describedFor
And/or,
As described R1Described in " substituted or unsubstituted C3～C15Aryl " or " hetero atom is oxygen, sulfur or nitrogen Atom, hetero atom number is 1-3, substituted or unsubstituted C2～C15Heteroaryl " described in " replacement " be quilt C1～C6Alkyl replaced time, described " C1～C6Alkyl " be methyl, ethyl, propyl group, isopropyl, Butyl, isobutyl group or the tert-butyl group；
And/or,
As described R1Described in " substituted or unsubstituted C3～C15Aryl " or " hetero atom is oxygen, sulfur or nitrogen Atom, hetero atom number is 1-3, substituted or unsubstituted C2～C15Heteroaryl " described in " replacement " be quilt C1～C6Alkoxyl replaced time, described " C1～C6Alkoxyl " be methoxyl group, ethyoxyl, propoxyl group, Isopropoxy, butoxy, isobutoxy or tert-butoxy；
And/or,
As described R1Described in " substituted or unsubstituted C3～C15Aryl " or " hetero atom is oxygen, sulfur or nitrogen Atom, hetero atom number is 1-3, substituted or unsubstituted C2～C15Heteroaryl " described in " replacement " be quilt C5～C6Aryloxy group replaced time, described " C5～C6Aryloxy group " be phenoxy group；
And/or,
As described R1Described in " substituted or unsubstituted C3～C15Aryl " or " hetero atom is oxygen, sulfur or nitrogen Atom, hetero atom number is 1-3, substituted or unsubstituted C2～C15Heteroaryl " described in " replacement " be quilt C1～C6Alkylthio group replaced time, described " C1～C6Alkylthio group " be methyl mercapto, ethylmercapto group, rosickyite base, Isopropyisulfanyl, butylthio, isobutylthio or tertiary butylthio；
And/or,
As described R1Described in " substituted or unsubstituted C3～C15Aryl " or " hetero atom is oxygen, sulfur or nitrogen Atom, hetero atom number is 1-3, substituted or unsubstituted C2～C15Heteroaryl " described in " replacement " be quilt C1～C6Alkyl silyl replaced time, described " C1～C6Alkyl silyl " be methylsilyl, trimethyl silicane Base, ethyl are silica-based, propyl group is silica-based, isopropyl is silica-based, butyl is silica-based, isobutyl group is silica-based or the tert-butyl group is silica-based；
And/or,
As described R1Described in " substituted or unsubstituted C3～C15Aryl " or " hetero atom is oxygen, sulfur or nitrogen Atom, hetero atom number is 1-3, substituted or unsubstituted C2～C15Heteroaryl " described in " replacement " be quilt " the one or more substituted C in fluorine, chlorine and bromine atoms1～C6Alkyl " replaced time, described " fluorine, chlorine and One or more substituted C in bromine atoms1～C6Alkyl " be that " one or more in fluorine, chlorine and bromine atoms take The methyl in generation ", " the one or more substituted ethyl in fluorine, chlorine and bromine atoms ", " in fluorine, chlorine and bromine atoms Individual or multiple substituted propyl group ", " the one or more substituted isopropyl in fluorine, chlorine and bromine atoms ", " fluorine, chlorine and One or more substituted butyl in bromine atoms ", " the one or more substituted isobutyl group in fluorine, chlorine and bromine atoms " Or " the one or more substituted tert-butyl group in fluorine, chlorine and bromine atoms "；
And/or,
As described R1Described in " substituted or unsubstituted C3～C15Aryl " or " hetero atom is oxygen, sulfur or nitrogen Atom, hetero atom number is 1-3, substituted or unsubstituted C2～C15Heteroaryl " described in " replacement " be quilt " the one or more substituted C in fluorine, chlorine and bromine atoms1～C6Alkoxyl " replaced time, described " fluorine, chlorine With the one or more substituted C in bromine atoms1～C6Alkoxyl " be " or many in fluorine, chlorine and bromine atoms Individual substituted methoxyl group ", " the one or more substituted ethyoxyl in fluorine, chlorine and bromine atoms ", " fluorine, chlorine and bromine are former One or more substituted propoxyl group in son ", " the one or more substituted isopropoxy in fluorine, chlorine and bromine atoms ", " the one or more substituted butoxy in fluorine, chlorine and bromine atoms ", " one or more in fluorine, chlorine and bromine atoms Substituted isobutoxy " or " the one or more substituted tert-butoxy in fluorine, chlorine and bromine atoms "；
And/or,
As described R1Described in " substituted or unsubstituted C3～C15Aryl " or " hetero atom is oxygen, sulfur or nitrogen Atom, hetero atom number is 1-3, substituted or unsubstituted C2～C15Heteroaryl " described in " replacement " be quilt C3～C6Aryl replaced time, described " C3～C6Aryl " be phenyl；
And/or,
As described R1Described in " substituted or unsubstituted C3～C15Aryl " or " hetero atom is oxygen, sulfur or nitrogen Atom, hetero atom number is 1-3, substituted or unsubstituted C2～C15Heteroaryl " described in " replacement " be quiltTime replaced, describedFor
And/or,
As described R1Described in " substituted or unsubstituted C3～C15Aryl " or " hetero atom is oxygen, sulfur or nitrogen Atom, hetero atom number is 1-3, substituted or unsubstituted C2～C15Heteroaryl " described in " replacement " be quiltTime replaced, describedFor
And/or,
As described R1Described in " substituted or unsubstituted C3～C15Aryl " or " hetero atom is oxygen, sulfur or nitrogen Atom, hetero atom number is 1-3, substituted or unsubstituted C2～C15Heteroaryl " described in " replacement " be quiltTime replaced, describedFor
And/or,
As described R5For " hetero atom be nitrogen-atoms, hetero atom number be the C of 13～C4Heterocyclylalkyl " time, Described " hetero atom be nitrogen-atoms, hetero atom number be the C of 13～C4Heterocyclylalkyl " be
And/or,
As described R2During for substituted methyl, described " substituted methyl " is
And/or,
As described R2During for substituted propyl group, described " substituted propyl group " is
4. the preparation method of the compound containing a fluoroalkyl as claimed in claim 3, it is characterised in that:
As described R1Described in " substituted or unsubstituted C3～C15Aryl " or " hetero atom is oxygen, sulfur or nitrogen Atom, hetero atom number is 1-3, substituted or unsubstituted C2～C15Heteroaryl " described in " replacement " be quilt When " the one or more substituted methyl in fluorine, chlorine and bromine atoms " is replaced, described " the substituted methyl of fluorine atom " For trifluoromethyl；
And/or,
As described R1Described in " substituted or unsubstituted C3～C15Aryl " or " hetero atom is oxygen, sulfur or nitrogen Atom, hetero atom number is 1-3, substituted or unsubstituted C2～C15Heteroaryl " described in " replacement " be quilt When " the one or more substituted methoxyl group in fluorine, chlorine and bromine atoms " is replaced, described " the substituted first of fluorine atom Epoxide " it is trifluoromethoxy；
And/or,
As described R1Described in " substituted or unsubstituted C3～C15Aryl " or " hetero atom is oxygen, sulfur or nitrogen Atom, hetero atom number is 1-3, substituted or unsubstituted C2～C15Heteroaryl " described in " replacement " be quiltTime replaced, describedForOr
And/or,
When described L is " substituted or unsubstituted 1,10-phenanthrene quinoline ", described " substituted 1,10-phenanthrene quinoline " is
And/or,
When described L is " substituted or unsubstituted pyridine ", described " substituted pyridine " is
And/or,
When described L is " substituted or unsubstituted bipyridyl ", described " substituted bipyridyl " is
5. the preparation method of the compound containing a fluoroalkyl as claimed in claim 1, it is characterised in that:
As described R1For " substituted or unsubstituted C3～C15Aryl " time, described " substituted or unsubstituted C3~ C15Aryl " be " substituted or unsubstituted C5～C14Aryl "；
And/or,
As described R1For " hetero atom is oxygen, sulfur or nitrogen-atoms, and hetero atom number is 1-3, replaces or unsubstituted C2～C15Heteroaryl " time, described " hetero atom is oxygen, sulfur or nitrogen-atoms, and hetero atom number is 1-3, Substituted or unsubstituted C2～C15Heteroaryl " be that " hetero atom is oxygen or nitrogen-atoms, and hetero atom number is the C of 13~ C12Heteroaryl ".
6. the preparation method of the compound containing a fluoroalkyl as claimed in claim 5, it is characterised in that:
As described R1For " substituted or unsubstituted C5～C14Aryl " time, described " substituted or unsubstituted C5~ C14Aryl " be " substituted or unsubstituted phenyl ", " substituted or unsubstituted naphthyl " or " substituted or unsubstituted fluorenes Base "；
And/or,
As described R1For " hetero atom is oxygen or nitrogen-atoms, and hetero atom number is the C of 13～C12Heteroaryl " time, It is described that " hetero atom is oxygen or nitrogen-atoms, and hetero atom number is the C of 13～C12Heteroaryl " be " and replace or do not take The pyridine radicals in generation ",
7. the preparation method of the compound containing a fluoroalkyl as claimed in claim 6, it is characterised in that:
As described R1During for " substituted or unsubstituted naphthyl ", described " unsubstituted naphthyl " is
And/or,
As described R1During for " substituted or unsubstituted fluorenyl ", described " unsubstituted fluorenyl " is
And/or,
As described R1During for " substituted or unsubstituted fluorenyl ", described " substituted fluorenyl " is
And/or,
As described R1During for " substituted or unsubstituted phenyl ", described " substituted phenyl " is 4-tert-butyl-phenyl, 4-cyano-phenyl, 3-fluoro-4-cyano-phenyl, 3-cyano-phenyl,3,4-Dichlorobenzene base,4-phenoxy group benzene Base, 4-trifluoromethyl, 3-trifluoromethyl, 4-trifluoromethyl, 2-aminomethyl phenyl, 3-aminomethyl phenyl, 4-aminomethyl phenyl,Or 3,5-Dichlorobenzene base；
And/or,
As described R1During for " substituted or unsubstituted pyridine radicals ", described " unsubstituted pyridine radicals " is 2-pyridine Base, 3-pyridine radicals or 4-pyridine radicals；
And/or,
As described R1During for " substituted or unsubstituted pyridine radicals ", described " substituted pyridine radicals " is
8. the preparation method of the compound containing a fluoroalkyl as claimed in claim 1, it is characterised in that:
Described compound A is following arbitrary compound:
Wherein, TMS represents that trimethyl is silica-based；
And/or,
Described compound B is following arbitrary compound:
And/or,
Described compound C is following arbitrary compound:
9. the preparation method of the compound containing a fluoroalkyl as claimed in claim 1, it is characterised in that:
In the described preparation method containing the compound of a fluoroalkyl, described solvent be ether solvent, alcohols solvent, One or more in chlorinated hydrocarbon solvent, aromatic hydrocarbon solvent and sulfoxide type solvents；
And/or,
In the described preparation method containing the compound of a fluoroalkyl, described solvent and the body of described compound B Long-pending mol ratio is 1mL/mmol～100mL/mmol；
And/or,
In the described preparation method containing the compound of a fluoroalkyl, described alkali is alkali metal hydroxide, alkali metal Carbonate, alkali metal hydrogencarbonate, alkali metal phosphate or " alkali metal and C1～C4The salt that alcohol is formed "；
And/or,
In the described preparation method containing the compound of a fluoroalkyl, described alkali and described compound B mole Ratio is 1～5；
And/or,
In the described preparation method containing the compound of a fluoroalkyl, described part is nitrogenous bidentate ligand or nitrogenous three Tooth part；
And/or,
In the described preparation method containing the compound of a fluoroalkyl, described part rubs with described compound B's Your ratio is 0.01～0.1；
And/or,
In the described preparation method containing the compound of a fluoroalkyl, described nickel salt be dimethyl second diether close Nickel dichloride., 1,2 pair of (diphenylphosphine) ethane closes Nickel dichloride., Nickel dichloride., nickelous bromide, Nickel diiodide., Nickel dichloride hexahydrate, three hydration bromines Change nickel, nickel acetate, nickel acetylacetonate, two triphenylphosphines conjunction Nickel dichloride. or Nickelous nitrate hexahydrates；
And/or,
In the described preparation method containing the compound of a fluoroalkyl, described compound A and described compound B Molar ratio be 0.5～2；
And/or,
In the described preparation method containing the compound of a fluoroalkyl, described catalyst is with described compound B's Molar ratio is 0.01～0.1；
And/or,
In the described preparation method containing the compound of a fluoroalkyl, described additive is pyridine, 4-trifluoromethyl Pyridine, 4-picoline, 2, the one or many in 6-lutidines, DMAP and 4-methoxypyridine Kind；
And/or,
In the described preparation method containing the compound of a fluoroalkyl, described additive is with described compound B's Molar ratio is 0.01～0.1；
And/or,
In the described preparation method containing the compound of a fluoroalkyl, the temperature of described Suzuki coupling reaction is 20 DEG C～120 DEG C；
And/or,
In the described preparation method containing the compound of a fluoroalkyl, the time of described Suzuki coupling reaction is 1 Hour～48 hours.
10. the preparation method of the compound containing a fluoroalkyl as claimed in claim 9, it is characterised in that:
In the described preparation method containing the compound of a fluoroalkyl, described ether solvent be glycol dimethyl ether and/ Or Isosorbide-5-Nitrae-dioxane；
And/or,
In the described preparation method containing the compound of a fluoroalkyl, described alcohols solvent is isopropanol；
And/or,
In the described preparation method containing the compound of a fluoroalkyl, described aromatic hydrocarbon solvent is toluene；
And/or,
In the described preparation method containing the compound of a fluoroalkyl, described sulfoxide type solvents is dimethyl sulfoxide；
And/or,
In the described preparation method containing the compound of a fluoroalkyl, described chlorinated hydrocarbon solvent is 1,2-bis-chloroethene Alkane；
And/or,
In the described preparation method containing the compound of a fluoroalkyl, described solvent and the body of described compound B Long-pending mol ratio is 1mL/mmol～10mL/mmol；
And/or,
Described alkali carbonate is one or more in potassium carbonate, sodium carbonate and cesium carbonate；
And/or,
Described alkali metal phosphate is potassium phosphate；
And/or,
Described " alkali metal and C1～C4Alcohol formed salt " described in " C1～C4Alcohol " be methanol, ethanol, propanol, Isopropanol or the tert-butyl alcohol；
And/or,
Described " alkali metal and C1～C4Alcohol formed salt " described in " alkali metal " be lithium, sodium, potassium, rubidium or caesium；
And/or,
In the described preparation method containing the compound of a fluoroalkyl, described alkali and described compound B mole Ratio is 2～3；
And/or,
In the described preparation method containing the compound of a fluoroalkyl, when described part is nitrogenous bidentate ligand, Described " nitrogenous bidentate ligand " be substituted or unsubstituted bipyridyl, substituted or unsubstituted 1,10-phenanthrene quinoline or
And/or,
In the described preparation method containing the compound of a fluoroalkyl, when described part is nitrogenous tridentate ligand, Described " nitrogenous tridentate ligand " is " substituted or unsubstituted pyridine "；
Described " substituted or unsubstituted bipyridyl ", " substituted or unsubstituted 1,10-phenanthrene quinoline " or " replacement or substituted Pyridine " described in " replacement " refer in heteroatomic non-ortho by C1～C10Alkyl, C1～C10Alkoxyl andIn one or more replaced, when there is multiple substituent group, described substituent group is identical or different； R8、R9、R10And R11It is respectively hydrogen or C1～C3Alkyl；R12And R13It is respectively hydrogen, C1～C3Alkyl, C5～C10Aryl or R12、R13And the carbon atom that they are connected is collectively forming 4-6 membered cyclic structure；
And/or,
In the described preparation method containing the compound of a fluoroalkyl, described part rubs with described compound B's Your ratio is 0.05～0.1；
And/or,
In the described preparation method containing the compound of a fluoroalkyl, described compound A and described compound B Molar ratio be 0.75～1.5；
And/or,
In the described preparation method containing the compound of a fluoroalkyl, described catalyst is with described compound B's Molar ratio is 0.05～0.1；
And/or,
And/or,
In the described preparation method containing the compound of a fluoroalkyl, described additive is with described compound B's Molar ratio is 0.05～0.1；
And/or,
In the described preparation method containing the compound of a fluoroalkyl, the temperature of described Suzuki coupling reaction is 70 DEG C～80 DEG C；
And/or,
And/or,
In the described preparation method containing the compound of a fluoroalkyl, the time of described Suzuki coupling reaction is 8 Hour～24 hours.
The preparation method of 11. compounds containing a fluoroalkyl as claimed in claim 10, it is characterised in that: described In preparation method containing the compound of a fluoroalkyl, when " the substituted or unsubstituted bipyridyl " described in described part, " replacement " described in " substituted or unsubstituted 1,10-phenanthrene quinoline " or " replacing or substituted pyridine " refers to heteroatomic By C in non-ortho1～C10Alkyl replaced time, described C1～C10Alkyl be C1～C6Alkyl；
And/or,
In the described preparation method containing the compound of a fluoroalkyl, when " replacing or not taking described in described part The bipyridyl in generation ", " replacement " described in " substituted or unsubstituted 1,10-phenanthrene quinoline " or " replace or substituted pyridine " be Refer in heteroatomic non-ortho by C1～C10Alkoxyl replaced time, described C1～C10Alkoxyl be C1~ C6Alkoxyl；
And/or,
As the R described in described part8、R9、R10And R11It is respectively C1～C3Alkyl time, described C1~ C3Alkyl be methyl, ethyl, propyl group or isopropyl；
And/or,
As the R described in described part12And R13It is respectively C5～C10Aryl time, described C5～C10's Aryl is phenyl；
And/or,
As the R described in described part12And R13It is respectively C1～C3Alkyl time, described C1～C3Alkane Base is methyl, ethyl, propyl group or isopropyl；
And/or,
As the R described in described part12And R13And they carbon atoms of being connected to be collectively forming 4-6 unit ring-type During structure, described six-membered cyclic structure is
12. the preparation method of the compound containing a fluoroalkyl as claimed in claim 11, it is characterised in that:
In the described preparation method containing the compound of a fluoroalkyl, when " replacing or not taking described in described part The bipyridyl in generation ", " replacement " described in " substituted or unsubstituted 1,10-phenanthrene quinoline " or " replace or substituted pyridine " be Refer in heteroatomic non-ortho by C1～C6Alkyl replaced time, described C1～C6Alkyl be methyl, second Base, propyl group, isopropyl, butyl, isobutyl group or the tert-butyl group；
And/or,
In the described preparation method containing the compound of a fluoroalkyl, when " replacing or not taking described in described part The bipyridyl in generation ", " replacement " described in " substituted or unsubstituted 1,10-phenanthrene quinoline " or " replace or substituted pyridine " be Refer in heteroatomic non-ortho by C1～C6Alkoxyl replaced time, described C1～C6Alkoxyl be methoxy Base, ethyoxyl, propoxyl group, isopropoxy, butoxy, isobutoxy or tert-butoxy.
The preparation method of 13. compounds containing a fluoroalkyl as claimed in claim 12, it is characterised in that: described In preparation method containing the compound of a fluoroalkyl, when described " nitrogenous bidentate ligand " is substituted or unsubstituted pyrrole During pyridine, described " substituted bipyridyl " is
And/or,
In the described preparation method containing the compound of a fluoroalkyl, when described " nitrogenous bidentate ligand " for replace or During unsubstituted 1,10-phenanthrene quinoline, described " unsubstituted 1,10-phenanthrene quinoline " is
And/or,
In the described preparation method containing the compound of a fluoroalkyl, when described " nitrogenous bidentate ligand " for replace or During unsubstituted 1,10-phenanthrene quinoline, described " substituted 1,10-phenanthrene quinoline " is
And/or,
In the described preparation method containing the compound of a fluoroalkyl, when described " nitrogenous bidentate ligand " isTime, describedFor
And/or,
In the described preparation method containing the compound of a fluoroalkyl, it is " to replace when described " nitrogenous tridentate ligand " Or unsubstituted pyridine " time, described " substituted pyridine " is
14. compounds as shown in formula C,
R1CHR2F
C
Wherein, R1Definition as described in any one of claim 1～8；R2Definition such as claim 1,2,3 and 8 Described in one.
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Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN107628926A (en) * 2017-09-29 2018-01-26 四川理工学院 A kind of preparation method of single fluoro ethyl substituted aromatic compound
CN108250059A (en) * 2018-02-01 2018-07-06 潍坊医学院 A kind of synthetic method of neurologic agent amitriptyline midbody compound
CN109694350A (en) * 2017-10-20 2019-04-30 中国科学院上海有机化学研究所 A kind of compound and preparation method thereof containing methyl fluoride
CN110803977A (en) * 2019-11-11 2020-02-18 四川轻化工大学 Method for preparing monofluoroalkyl substituted aromatic compound through reduction coupling
WO2021126080A1 (en) * 2019-12-17 2021-06-24 National University Of Singapore A new method of 18f labelling and intermediate salts

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2014023723A1 (en) * 2012-08-08 2014-02-13 Novartis Ag Subtituted azines as pesticides

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2014023723A1 (en) * 2012-08-08 2014-02-13 Novartis Ag Subtituted azines as pesticides

Non-Patent Citations (4)

* Cited by examiner, † Cited by third party
Title
JING-JING MA等: "Transition-Metal-Free C-H Oxidative Activation: Persulfate-Promoted Selective Benzylic Mono- and Difluorination", 《ORGANIC & BIOMOLECULAR CHEMISTRY》 *
YANCHUAN ZHAO等: "Copper-Catalyzed Debenzoylative Monofl uoromethylation of Aryl Iodides Assisted by the Removable (2-Pyridyl)sulfonyl Group", 《ACS CATAL. 》 *
YANCHUAN ZHAO等: "Copper-Mediated Fluoroalkylation of Aryl Iodides Enables Facile Access to Diverse Fluorinated Compounds: The Important Role of the (2-Pyridyl)sulfonyl Group", 《ORGANIC LETTERS》 *
YI-MING SU等: "Nickel-Catalyzed Monofluoromethylation of Aryl Boronic Acids", 《ANGEW. CHEM. INT. ED.》 *

Cited By (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN107628926A (en) * 2017-09-29 2018-01-26 四川理工学院 A kind of preparation method of single fluoro ethyl substituted aromatic compound
CN109694350A (en) * 2017-10-20 2019-04-30 中国科学院上海有机化学研究所 A kind of compound and preparation method thereof containing methyl fluoride
CN109694350B (en) * 2017-10-20 2023-05-09 中国科学院上海有机化学研究所 Compound containing fluoromethyl and preparation method thereof
CN108250059A (en) * 2018-02-01 2018-07-06 潍坊医学院 A kind of synthetic method of neurologic agent amitriptyline midbody compound
CN108250059B (en) * 2018-02-01 2021-08-20 潍坊医学院 Synthesis method of nerve drug amitriptyline intermediate compound
CN110803977A (en) * 2019-11-11 2020-02-18 四川轻化工大学 Method for preparing monofluoroalkyl substituted aromatic compound through reduction coupling
WO2021126080A1 (en) * 2019-12-17 2021-06-24 National University Of Singapore A new method of 18f labelling and intermediate salts

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