CN106699532B - A kind of preparation method of 1,1- difluoro Tetrahydronaphthalencompounds compounds - Google Patents
A kind of preparation method of 1,1- difluoro Tetrahydronaphthalencompounds compounds Download PDFInfo
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- C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
- C07C45/61—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups
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- C07C45/673—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton by change of size of the carbon skeleton
- C07C45/676—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton by change of size of the carbon skeleton by elimination of carboxyl groups
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- C07C67/333—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group by isomerisation; by change of size of the carbon skeleton
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Abstract
The invention discloses one kind 1, the preparation method of 1- difluoro Tetrahydronaphthalencompounds compounds, it include: that the allyl benzene formaldehyde of II structure of formula, phenyl boric acid, monobromo difluoro acetate, palladium catalyst, alkali and the first solvent are added to mix, the first reaction system is formed, it is post-treated after the reaction was completed to obtain 6- fluoroalkyl ketone；6- fluoroalkyl ketone is dissolved in methanol, the stirring of LiOH aqueous solution is added, the hydrolysate that acidizing extraction is concentrated to get is dissolved in the second solvent, silver catalyst is added, sodium thiosulfate forms the second reaction system, it is post-treated after the reaction was completed to obtain 1,1- difluoro Tetrahydronaphthalencompounds compounds.The present invention is by 1, n- Hydrogen transfer free radical addition strategy is used for the long-range aryl fluoroalkyl of alkene, and what is be simple and efficient is prepared for 6- fluoroalkyl ketone compounds and is used in the synthesis of target compound, and preparation method is novel, good yields have a good application prospect.
Description
Technical field
The present invention relates to technical field of organic synthesis, and in particular to the preparation side of one kind 1,1- difluoro Tetrahydronaphthalencompounds compounds
Method.
Background technique
Difluoro methylene (- CF2) be typically used in the design of drug and bioactive molecule, on the one hand, difluoro is sub-
Methyl has good metabolic stability, is usually made the bioisostere of oxygen atom, carbonyl and methylene；Another party
Face, in functionalized difluoromethyl, the sucting electronic effect of difluoro methylene also affects the electro of adjacent functionality R
Matter, chemical property and reactivity.Therefore, the compound containing difluoro methylene segment is in biological medicine, pesticide, material etc.
Field suffers from very extensive application.Difluoro methylene is introduced into organic compound, it has also become a kind of raising compound
The optional approach of pharmaceutical properties.
In recent years, due to reacting the favor by chemists using fluoroalkylization that is transition metal-catalyzed or participating in,
Such reaction has mild reaction condition, reaction applicability, functional group compatibility and good selective.It is transition metal-catalyzed
The coupling of aryl boric acid or organic halide-containing and fluoroalkyl reagent has obtained wide coverage.It is urged by transition metal
Change the direct fluoroalkylization reaction of organic compound c h bond activation also to have received widespread attention.The aryl fluoroalkyl of alkene
Reaction becomes two fluothane of synthesis because can introduce two height of aryl and difluoromethane base simultaneously and synthesize useful functional group
One of maximally efficient method of based compound.
Tetralin quasi-compound is a kind of important Organic Chemicals, is widely used in pesticide, medicine, auxiliary agent, dyestuff
Etc. various fields.Tetralin quasi-compound has important medical value, is usually used in anti-inflammatory class, antirheumatic, anti-glycosuria class etc.
The synthesis of pharmaceutical intermediate.Simultaneously using naphthane as raw material, polycyclic aromatic compounds and steroid can further be synthesized by dehydrogenation
Same clan's compound.In view of the excellent medical value of tetralin quasi-compound, develop simple, efficient 1,1- difluoro naphthane chemical combination
It is extremely urgent to develop new drug molecule for the synthetic route of object.
Summary of the invention
The present invention provides the preparation methods of one kind 1,1- difluoro Tetrahydronaphthalencompounds compounds, realize palladium chtalyst allyl first
The long-range aryl fluoroalkylization of benzaldehyde is reacted, and 1, n- Hydrogen transfer free radical addition strategy is used for the long-range virtue of alkene
Base fluoroalkyl, then resulting 6- fluoroalkyl ketone is hydrolyzed, 5- aryl -2, the 2- difluoro valeric acid generated by acidification is in silver
Catalysis is lower to realize that decarbonylation is cyclized to form difluoro Tetrahydronaphthalencompounds compounds.
The preparation method of one kind 1,1- difluoro Tetrahydronaphthalencompounds compounds, includes the following steps:
(1) the allyl benzene formaldehyde of II structure of formula, phenyl boric acid, monobromo difluoro acetate, palladium catalyst, alkali and first is molten
Mixing is added in agent, forms the first reaction system, after the reaction was completed the post-treated 6- fluoroalkyl ketone for obtaining structure shown in formula I；
Wherein, in formula II, R is one of hydrogen atom, chlorine atom, methyl, methoxyl group, and R and R in formula II has in formula I
Identical meanings；
(2) the 6- fluoroalkyl ketone of structure shown in formula I is dissolved in methanol, the stirring of LiOH aqueous solution, acidizing extraction concentration is added
Obtained hydrolysate is dissolved in the second solvent, silver catalyst is added, sodium thiosulfate forms the second reaction system, reaction completion
The 1,1- difluoro Tetrahydronaphthalencompounds compounds of III structure of formula are obtained by post-processing；
Wherein, R and R in formula I has identical meanings in formula III.
Step (1) is the preparation method of the 6- fluoroalkyl ketone of structure shown in formula I.Main first reaction that step (1) is related to
Specific synthetic route is as follows:
From the allyl benzene formaldehyde of II structure of formula, monobromo difluoromethyl compound, allyl benzene formaldehyde and boron are completed
Three component reactions of acid, the preparation method simply and effectively realize the synthesis of the 6- fluoroalkyl ketone of structure shown in formula I.
In step (1), main first be related to reacts optimal conditions are as follows:
The reaction condition of first reaction system are as follows: reaction temperature is 10~40 DEG C, and the reaction time is 5h~15h.
Further preferably, the reaction condition of first reaction system are as follows: reaction temperature be 20~35 DEG C, the reaction time be 8h~
12h。
The palladium catalyst is bi triphenyl phosphorus palladium chloride, and the alkali is cesium carbonate, and first solvent is
Methylene chloride.
The allyl benzene formaldehyde of II structure of formula, phenyl boric acid, monobromo difluoro acetate, palladium catalyst and alkali mole
Than for 1:1~1.4:1.7~2.3:0.02~0.06:1.2~1.8.Further preferably, the allyl benzene of II structure of formula
Formaldehyde, phenyl boric acid, monobromo difluoro acetate, palladium catalyst and alkali molar ratio be 1:1.2:2:0.04:1.5.
The post-processing includes: that water quenching goes out, extracts, organic phase is washed, dry and column chromatography for separation using adding.
Methylene chloride can be used as extractant in the extraction.
Saturated common salt washing can be used in the washing.
The condition of the column chromatography for separation are as follows: silica gel 300-400 mesh, eluent: the volume ratio of petrol ether/ethyl acetate
It is 50/1.
The 6- fluoroalkyl ketone of step (1) preparation can be used for the synthesis of 1,1- difluoro Tetrahydronaphthalencompounds compounds.
Step (2) is the preparation method of 1,1- difluoro Tetrahydronaphthalencompounds compounds.The specific synthesis road of second reaction of step (2)
Line is as follows:
In step (2), main second be related to reacts optimal conditions are as follows:
The concentration of the LiOH aqueous solution is 0.5~2molL-1, further preferably, the LiOH aqueous solution it is dense
Degree is 1molL-1。
In 10~40 DEG C of 1~3h of stirring, further preferably, in 20~30 DEG C of 1~3h of stirring, still more preferably, 25
DEG C stirring 2h.
The condition of second reaction system are as follows: reaction temperature is 10~40 DEG C, and the reaction time is 7h~17h.Into one
Step is preferred, the condition of second reaction system are as follows: reaction temperature is 20~35 DEG C, and the reaction time is 10h~14h.
The 6- fluoroalkyl ketone of the structure shown in formula I, silver catalyst, sodium thiosulfate molar ratio be 1:0.15~0.4:
1.5~3.5.Further preferably, the 6- fluoroalkyl ketone, silver catalyst of the structure shown in formula I, the molar ratio of sodium thiosulfate are
1:0.2~0.3:2~3.Still more preferably, 6- fluoroalkyl ketone, the silver catalyst, sodium thiosulfate of the structure shown in formula I
Molar ratio be 1:0.25:2.5.
The silver catalyst is silver nitrate, the solvent that second solvent is mixed by acetonitrile and water.Further
It is preferred that second solvent is by the solvent that volume ratio is that 1:1 acetonitrile and water mix.
The post-processing includes: to use to add the skills such as water quenching goes out, extracts, organic phase is washed, dry and column chromatography for separation
Art is post-processed, to obtain the product of high-purity.
Ethyl acetate can be used as extractant in the extraction.
Saturated common salt washing can be used in the washing.
The condition of the column chromatography for separation are as follows: silica gel 300-400 mesh, eluent: the volume ratio of petrol ether/ethyl acetate
It is 50/1.
Compared with the existing technology, the present invention has the advantage that
1, the strategy of 1, n- Hydrogen transfer free radical addition is applied to the long-range aryl fluoroalkyl of alkene, is realized
The synthesis of 6- fluoroalkyl ketone.2, the hydrolysis acidification of 6- fluoroalkyl ketone derivatives is realized.3, it is catalyzed using silver and realizes 5-
The cyclisation of aryl -2,2- difluoro valeric acid decarbonylation, constructs 1,1- difluoro tetrahydro naphthalene skeleton.4, reaction condition is mild, easy to operate, bottom
Object is applied widely, and functional group compatibility is good, has applications well prospect；Therefore the present invention have biggish theory innovation be worth with
And implementary value.
Specific embodiment
Embodiment 1
A dry reaction tube is taken, allyl benzene formaldehyde 1a (36.5mg, 0.25mmol), phenyl boric acid 2a are weighed into
(37.0mg, 0.3mmol), ethyl bromide difluoride 3a (101mg, 0.5mmol), bi triphenyl phosphorus palladium chloride (7mg,
0.01mmol), cesium carbonate (122.2mg, 0.375mmol) is then added 1mL dry methylene chloride and forms reaction system.The body
It ties up at 25 DEG C of room temperature after stirring 10h, 10mL water quenching is added to go out, three times with methylene chloride (10mL) extraction, with saturation food after merging
Organic phase is washed with water, anhydrous sodium sulfate is dry.Organic phase concentration after with silica gel (300-400 mesh) column chromatography for separation (eluent:
The volume ratio of petrol ether/ethyl acetate is 50/1) to obtain 70mg colourless liquid 4aaa, yield 81%.Product Spectrum Analysis1H
NMR(600MHz,CDCl3)δ7.77–7.80(m,2H),7.55–7.62(m,1H),7.41–7.49(m,3H),7.26–7.35
(m, 3H), 4.25 (q, J=7.1Hz, 2H), 2.73 (t, J=7.8Hz, 2H), 1.96-2.08 (m, 2H), 1.72-1.80 (m,
2H), 1.29 (t, J=7.1Hz, 3H)；13C NMR(151MHz,CDCl3) δ 198.3,164.2 (t, J=33.1Hz), 140.2,
138.4,137.7,133.2,130.4,130.1,130.1,128.9,128.4,125.6,11 6.1 (t, J=250.2Hz),
62.7,34.0 (t, J=23.3Hz), 32.4,23.4 (t, J=4.2Hz), 13.9；19F NMR(565MHz,CDCl3)δ–
105.9；HRMS(ESI)calcd for C20H21F2O3(M+H)+347.1459,found 347.1459。
Reaction equation is as follows:
Embodiment 2
Except the allyl benzene formaldehyde derivatives shown in structural formula 1b replace allyl shown in structural formula 1a in embodiment 1
Outside benzaldehyde, remaining operating procedure is with embodiment 1, yield: 77%, colourless liquid；Product Spectrum Analysis1H NMR(600MHz,
CDCl3)δ7.75–7.82(m,2H),7.60–7.65(m,1H),7.47–7.50(m,2H),7.38–7.44(m,1H),7.25–
7.29 (m, 2H), 4.26 (q, J=7.2Hz, 2H), 2.67 (t, J=7.8Hz, 2H), 1.95-2.06 (m, 2H), 1.71-1.76
(m, 2H), 1.30 (t, J=7.1Hz, 3H)；13C NMR(151MHz,CDCl3) δ 196.8,164.1 (t, J=33.0Hz),
140.0,138.5,137.0,133.7,131.6,131.5,130.4,130.1,128.7,12 8.4,116.0 (t, J=
250.4Hz), 62.8,33.9 (t, J=23.4Hz), 31.8,23.2 (t, J=4.2Hz), 13.9；19F NMR(565MHz,
CDCl3)δ–105.9；HRMS(ESI)calcd for C20H20ClF2O3(M+H)+381.1069,found 381.1081。
Reaction equation is as follows:
Embodiment 3
Except the allyl benzene formaldehyde derivatives shown in structural formula 1c replace allyl shown in structural formula 1a in embodiment 1
Outside benzaldehyde, remaining operating procedure is with embodiment 1, yield: 81%, colourless liquid；Product Spectrum Analysis1H NMR(600MHz,
CDCl3)δ7.74–7.79(m,2H),7.58–7.62(m,1H),7.44–7.49(m,2H),7.33(s,1H),7.26–7.26
(m, 2H), 4.26 (q, J=7.1Hz, 2H), 2.72 (t, J=7.9Hz, 2H), 1.98-2.09 (m, 2H), 1.72-1.81 (m,
2H), 1.30 (t, J=7.1Hz, 3H)；13C NMR(151MHz,CDCl3) δ 197.2,164.1 (t, J=32.9Hz), 142.6,
137.4,136.6,136.4,133.5,130.4,130.1,130.1,128.5,125.9,11 6.0 (t, J=250.3Hz),
62.8,33.9 (t, J=23.3Hz), 32.2,23.2 (t, J=4.2Hz), 13.9；19F NMR(565MHz,CDCl3)δ–
105.9；HRMS(ESI)calcd for C20H20ClF2O3(M+H)+381.1069,found 381.1080。
Reaction equation is as follows:
Embodiment 4
Except the allyl benzene formaldehyde derivatives shown in structural formula 1d replace allyl shown in structural formula 1a in embodiment 1
Outside benzaldehyde, remaining operating procedure is with embodiment 1, yield: 80%, colourless liquid；Product Spectrum Analysis1H NMR(600MHz,
CDCl3)δ7.76–7.78(m,2H),7.56–7.58(m,1H),7.43–7.46(m,2H),7.21–7.22(m,1H),7.13
(s, 1H), 7.06-7.07 (m, 1H), 4.25 (q, J=7.1Hz, 2H), 2.74 (t, J=7.8Hz, 2H), 2.40 (s, 3H),
1.98-2.09 (m, 2H), 1.73-1.79 (m, 2H), 1.29 (t, J=7.1Hz, 3H)；13C NMR(151MHz,CDCl3)δ
198.3,164.2 (t, J=33.0Hz), 140.8,140.7,138.1,135.3,132.9,131.0,130.1,129.5,
128.3,126.2,116.1 (t, J=250.2Hz), 62.7,34.1 (t, J=23.3Hz), 32.4,23.5 (t, J=4.2Hz),
21.4,13.9；19F NMR(565MHz,CDCl3)δ–105.8；HRMS(ESI)calcd for C21H23F2O3(M+H)+
361.1615,found 361.1615。
Reaction equation is as follows:
Embodiment 5
Except the allyl benzene formaldehyde derivatives shown in structural formula 1e replace allyl shown in structural formula 1a in embodiment 1
Outside benzaldehyde, remaining operating procedure is with embodiment 1, yield: 72%, colourless liquid；Product Spectrum Analysis1H NMR(600MHz,
CDCl3)δ7.80–7.81(m,2H),7.58–7.60(m,1H),7.45–7.47(m,2H),7.22–7.23(m,1H),6.96–
7.00 (m, 1H), 6.82-6.82 (m, 1H), 4.25 (q, J=7.1Hz, 2H), 3.78 (s, 3H), 2.63 (t, J=7.7Hz,
2H), 1.95-2.04 (m, 2H), 1.68-1.74 (m, 2H), 1.29 (t, J=7.1Hz, 3H)；13C NMR(151MHz,CDCl3)δ
198.0,164.2 (t, J=33.0Hz), 157.2,139.4,137.4,133.3,131.8,131.1,130.1,128.5,
116.1 (t, J=250.1Hz), 116.1,113.9,62.7,55.4,33.9 (t, J=23.3Hz), 31.5,23.4 (t, J=
4.0Hz),13.9；19F NMR(565MHz,CDCl3)δ–105.8；HRMS(ESI)calcd for C21H23F2O4(M+H)+
377.1564,found 377.1566。
Reaction equation is as follows:
Embodiment 6
The 6- fluoroalkyl ketone 2a (692mg, 2.0mmol) that above-mentioned preparation is added in reaction flask is dissolved in methanol (6mL), is added
Enter 1M lithium hydroxide aqueous solution (6mL), 25 DEG C of reaction 2h of room temperature add the hydrochloric acid of 1M, are extracted with ethyl acetate, saturated common salt
Water washing organic phase, anhydrous sodium sulfate drying are concentrated to get 5- aryl -2,2- difluoro valeric acid.
A dry reaction tube is taken, it is molten to be weighed into hydrolysate 5- aryl -2,2- difluoro valeric acid (63.6mg, 0.2mmol)
In 4mL mixed solvent (acetonitrile: water=1:1), be added silver nitrate (8.5mg, 0.05mmol) and sodium thiosulfate (95mg,
It 0.5mmol) reacts, after reaction stirs 12h at 25 DEG C of room temperature, adds water quenching to go out, be extracted with ethyl acetate, saturated common salt water washing
Organic phase, anhydrous sodium sulfate are dry.Organic phase concentration after with silica gel (300-400 mesh) column chromatography for separation (eluent: petroleum ether/
The volume ratio of ethyl acetate is 50/1) to obtain 38mg colourless liquid 3a, yield 70%.Product Spectrum Analysis1H NMR(600MHz,
CDCl3)δ7.83–7.88(m,1H),7.79–7.81(m,2H),7.60–7.62(m,1H),7.46–7.49(m,2H),7.37–
7.42(m,2H),2.80–2.82(m,2H),2.25–2.35(m,2H),1.92–1.98(m,2H)；13C NMR(151MHz,
CDCl3) δ 197.8,138.3,137.2,136.6 (t, J=5.8Hz), 133.6,133.6 (t, J=26.0Hz), 130.1,
129.9 (t, J=1.7Hz), 128.6,127.8 (t, J=3.6Hz), 126.1 (t, J=1.3Hz), 119.6 (t, J=
237.4Hz), 33.1 (t, J=23.9Hz), 26.6,19.7 (t, J=4.7Hz)；19F NMR(565MHz,CDCl3)δ–83.5；
HRMS(ESI)calcd for C17H15F2O(M+H)+273.1091,found 273.1094。
Reaction equation is as follows:
Embodiment 7
Except the 6- fluoroalkyl ketone shown in structural formula 2b replaces 6- fluoroalkyl ketone shown in structural formula 2a in embodiment 6
Outside, remaining operating procedure is with embodiment 6, yield: 61%, colourless liquid；Product Spectrum Analysis1H NMR(600MHz,CDCl3)δ
7.78–7.79(m,2H),7.61–7.64(m,1H),7.47–7.50(m,2H),7.41–7.42(m,1H),7.26–7.28(m,
1H),2.79–2.81(m,2H),2.27–2.39(m,2H),1.86–1.90(m,2H)；13C NMR(151MHz,CDCl3)δ
196.9,139.8 (t, J=5.4Hz), 137.2,136.8,135.9,133.9,130.4 (t, J=24.4Hz), 130.1,
(130.1,129.2,128.8,119.4 t, J=240.6Hz), 34.9 (t, J=24.8Hz), 28.0,19.3 (t, J=
4.7Hz)；19F NMR(565MHz,CDCl3)δ–86.6；HRMS(ESI)calcd for C17H13ClF2NaO(M+Na)+
329.0521,found 329.0516。
Reaction equation is as follows:
Embodiment 8
Except the 6- fluoroalkyl ketone shown in structural formula 2c replaces 6- fluoroalkyl ketone shown in structural formula 2a in embodiment 6
Outside, remaining operating procedure is with embodiment 6, yield: 68%, colourless liquid；Product Spectrum Analysis1H NMR(600MHz,CDCl3)δ
7.75–7.86(m,3H),7.63–7.65(m,1H),7.49–7.51(m,2H),7.34–7.35(m,1H),2.70–2.77(m,
2H),2.23–2.33(m,2H),1.90–1.98(m,2H)；13C NMR(151MHz,CDCl3)δ196.2,140.1,136.5,
135.2 (t, J=26.3Hz), 134.9 (t, J=5.6Hz), 134.0,132.2,130.1,129.7,128.8,127.7 (t, J
=3.8Hz), 118.9 (t, J=238.4Hz), 32.8,26.1,19.5 (t, J=4.6Hz)；19F NMR(565MHz,CDCl3)
δ–84.1；HRMS(ESI)calcd for C17H14ClF2O(M+H)+307.0701,found 307.0686。
Reaction equation is as follows:
Embodiment 9
Except the 6- fluoroalkyl ketone shown in structural formula 2d replaces 6- fluoroalkyl ketone shown in structural formula 2a in embodiment 6
Outside, remaining operating procedure is with embodiment 6, yield: 66%, colourless liquid；Product Spectrum Analysis1H NMR(600MHz,CDCl3)δ
7.79–7.80(m,2H),7.57–7.63(m,1H),7.45–7.48(m,2H),7.23–7.24(m,1H),7.16–7.17(m,
1H), 2.79-2.81 (m, 2H), 2.62 (t, J=2.6Hz, 3H), 2.25-2.36 (m, 2H), 1.84-1.88 (m, 2H)；13C
NMR(151MHz,CDCl3) δ 198.0,141.1,137.7 (t, J=6.4Hz), 137.5,136.2,133.4,131.2 (t, J=
24.7Hz), 130.1,129.60 (t, J=0.9Hz), 129.3 (t, J=1.6Hz), 128.6,121.5 (t, J=238.5Hz),
35.1 (t, J=25.0Hz), 27.9,20.8 (t, J=4.9Hz), 19.7 (t, J=4.7Hz)；19F NMR(565MHz,CDCl3)
δ–84.4；HRMS(ESI)calcd for C18H17F2O(M+H)+287.1247,found 287.1233。
Reaction equation is as follows:
Embodiment 10
Except the 6- fluoroalkyl ketone shown in structural formula 2e replaces 6- fluoroalkyl ketone shown in structural formula 2a in embodiment 6
Outside, remaining operating procedure is with embodiment 6, yield: 61%, colourless liquid；Product Spectrum Analysis1H NMR(600MHz,CDCl3)δ
7.81–7.82(m,2H),7.60–7.62(m,1H),7.46–7.49(m,2H),7.33–7.34(m,1H),6.93–6.94(m,
1H),3.84(s,3H),2.68–2.70(m,2H),2.23–2.31(m,2H),1.89–1.96(m,2H)；13C NMR(151MHz,
CDCl3) δ 197.4,157.5,139.6,136.9,134.5 (t, J=25.6Hz), 133.6,130.1,128.6,128.4 (t, J
=5.7Hz), 119.7 (t, J=237.7Hz), 117.1,111.5 (t, J=3.7Hz), 55.6,33.1 (t, J=23.8Hz),
(25.8,19.9 t, J=4.6Hz)；19F NMR(565MHz,CDCl3)δ–83.6；HRMS(ESI)calcd for
C18H16F2NaO2(M+Na)+325,1016,found325.1011。
Reaction equation is as follows:
Claims (10)
1. one kind 1, the preparation method of 1- difluoro Tetrahydronaphthalencompounds compounds, which comprises the steps of:
(1) the allyl benzene formaldehyde of II structure of formula, phenyl boric acid, monobromo difluoro acetate, palladium catalyst, alkali and the first solvent are added
Enter mixing, forms the first reaction system, after the reaction was completed the post-treated 6- fluoroalkyl ketone for obtaining structure shown in formula I；The palladium
Catalyst is bi triphenyl phosphorus palladium chloride；
Wherein, in formula II, R is one of hydrogen atom, chlorine atom, methyl, methoxyl group, and R has identical with R in formula II in formula I
Meaning；
(2) the 6- fluoroalkyl ketone of structure shown in formula I is dissolved in methanol, the stirring of LiOH aqueous solution is added, acidizing extraction is concentrated to get
Hydrolysate be dissolved in the second solvent, be added silver catalyst, sodium thiosulfate formed the second reaction system, pass through after the reaction was completed
Post-processing obtains the 1,1- difluoro Tetrahydronaphthalencompounds compounds of III structure of formula；
Wherein, R and R in formula I has identical meanings in formula III.
2. the preparation method of 1,1- difluoro Tetrahydronaphthalencompounds compounds according to claim 1, which is characterized in that in step (1),
The reaction condition of first reaction system are as follows: reaction temperature is 10~40 DEG C, and the reaction time is 5h~15h.
3. the preparation method of 1,1- difluoro Tetrahydronaphthalencompounds compounds according to claim 1, which is characterized in that in step (1),
The alkali is cesium carbonate.
4. the preparation method of 1,1- difluoro Tetrahydronaphthalencompounds compounds according to claim 1, which is characterized in that in step (1),
The allyl benzene formaldehyde of II structure of formula, phenyl boric acid, monobromo difluoro acetate, palladium catalyst and alkali molar ratio be 1:1
~1.4:1.7~2.3:0.02~0.06:1.2~1.8.
5. the preparation method of 1,1- difluoro Tetrahydronaphthalencompounds compounds according to claim 1, which is characterized in that step (1) and
(2) in, the post-processing includes: that water quenching goes out, extracts, organic phase is washed, dry and column chromatography for separation using adding.
6. the preparation method of 1,1- difluoro Tetrahydronaphthalencompounds compounds according to claim 1, which is characterized in that in step (2),
The concentration of the LiOH aqueous solution is 0.5~2molL-1。
7. the preparation method of 1,1- difluoro Tetrahydronaphthalencompounds compounds according to claim 1, which is characterized in that in step (2),
In 10~40 DEG C of 1~3h of stirring.
8. the preparation method of 1,1- difluoro Tetrahydronaphthalencompounds compounds according to claim 1, which is characterized in that in step (2),
The condition of second reaction system are as follows: reaction temperature is 10~40 DEG C, and the reaction time is 7h~17h.
9. the preparation method of 1,1- difluoro Tetrahydronaphthalencompounds compounds according to claim 1, which is characterized in that in step (2),
The 6- fluoroalkyl ketone of the structure shown in formula I, silver catalyst, sodium thiosulfate molar ratio be 1:0.15~0.4:1.5~
3.5。
10. the preparation method of 1,1- difluoro Tetrahydronaphthalencompounds compounds according to claim 1, which is characterized in that step (2)
In, the silver catalyst is silver nitrate, the solvent that second solvent is mixed by acetonitrile and water.
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