CN104557924A - Fluoro alkyl ether copper (I) as well as preparation method and application thereof - Google Patents
Fluoro alkyl ether copper (I) as well as preparation method and application thereof Download PDFInfo
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- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
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- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/62—Oxygen or sulfur atoms
- C07D213/63—One oxygen atom
- C07D213/64—One oxygen atom attached in position 2 or 6
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- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
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- C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
- C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
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- C07D277/60—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings condensed with carbocyclic rings or ring systems
- C07D277/62—Benzothiazoles
- C07D277/68—Benzothiazoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached in position 2
Abstract
The invention discloses fluoro alkyl ether copper (I), a preparation method of the fluoro alkyl ether copper (I) and an application of the fluoro alkyl ether copper (I) to fluoro alkyl etherification reaction. The fluoro alkyl ether copper (I) has a structural formula as shown in the specification, wherein RF is CF3, CF2CF3, CF2CHF2 or CF2CF2CF3, and R1 and R2 are H or alkyl independently. The fluoro alkyl ether copper (I) is prepared as follows: enabling cuprous chloride, sodium tert-butoxide, a nitrogen-nitrogen bidentate ligand and fluoro alkyl alcohol to react in a solvent of tetrahydrofuran, and then separating and purifying. The fluoro alkyl ether copper (I) is capable of promoting the fluoro alkyl etherification of a halogenated aromatic hydrocarbon and a halogenated heterocyclic compound efficiently to form an aromatic hydrocarbon or heterocycle containing fluoro alkyl ether derivative and has a good industrial application prospect.
Description
Technical field
The present invention is specifically related to a kind of fluoro-alkyl ether copper (I) and preparation method thereof and its application in fluoro-alkyl etherification reaction.
Background technology
Because fluorine atom electronegativity is high, atomic radius is little, makes fluorochemicals all show unique physico-chemical property, thus have very important application in the fields such as medicine, agricultural chemicals, functional materials.In the functional group of contain fluorine atoms, fluoro-alkyl ether (-OCH
2r
f) due to its strong electronegativity and strongly lipophilic, receive a large amount of concerns of people, such as improving the (R)-5-(2-(2-(2-ethoxyphenoxy)ethylamino)propyl)-2-methoxybenzensulfonamide (Silodosin) of benign prostatic hyperplasia, in the most drug molecules such as anti-arrhythmic flecainide (Flecainide), all contain trifluoro ethoxy (-OCH
2cF
3).
Current existing Trifluo-roethoxylation or the reaction of other fluoro-alkyl ether, fluorination reagent, the catalyzer of the excessive costliness of most use, and substrate applicability is wide, therefore, be starved of development one class economy, Trifluo-roethoxylation or fluoro-alkyl ether copper efficiently.
Summary of the invention
The object of the present invention is to provide a kind of fluoro-alkyl ether copper (I) and preparation method thereof and application, is take fluoroalkyl alcohol as raw material, carries out chelating formation, and can stably preserve with raw materials such as nitrogen nitrogen bitooth ligands.Meanwhile, this fluoro-alkyl ether copper (I) can promote the fluoro-alkyl etherification reaction of halogenated aryl hydrocarbon and halogenated heterocyclic compound efficiently.
For achieving the above object, the present invention adopts following technical scheme:
A kind of fluoro-alkyl ether copper (I), its structural formula is:
，
Wherein, R
ffor CF
3, CF
2cF
3, CF
2cHF
2or CF
2cF
2cF
3,
R
1and R
2independently take from H or alkyl separately.
R in the structural formula of described fluoro-alkyl ether copper (I)
1and R
2be all H, or be all alkyl, or R
1for hydrogen, R
2for alkyl, or R
1and R
2be independently H or the alkyl containing 1-4 carbon atom.
The preparation method of described fluoro-alkyl ether copper (I) comprises the following steps:
1) add cuprous chloride, tetrahydrofuran (THF) and sodium tert-butoxide in the reactor, stirring at room temperature reacts 1 hour under nitrogen protection, filters, obtains trimethyl carbinol cuprous solution;
2) in gained trimethyl carbinol cuprous solution, nitrogen nitrogen bitooth ligand is dripped, mixed solution at room temperature stirring reaction after 10 minutes, fluoroalkyl alcohol is dripped in mixed solution, continue stirring 20 minutes, filter, filter vacuum is except desolventizing, and after gained solid washed with ether, recrystallization obtains described fluoro-alkyl ether copper (I).
Wherein, cuprous chloride, sodium tert-butoxide, nitrogen nitrogen bitooth ligand and fluoroalkyl alcohol in molar ratio 1:1:2:1 add; Every mmol cuprous chloride uses tetrahydrofuran (THF) 30-50 mL;
The structural formula of described nitrogen nitrogen bitooth ligand is:
，
Wherein, R
1and R
2independently take from H or alkyl separately.
The application of described fluoro-alkyl ether copper (I) is in the DMF solvent containing sodium tert-butoxide, described fluoro-alkyl ether copper (I) is reacted with compound R-X, generates corresponding fluoro-alkyl ether derivant;
Reaction equation its reaction equation as follows is:
，
Wherein X to be Br or I, R be in following formula a-formula aa any one:
。
Its concrete operation step is: in nitrogen atmosphere, put into tetrafluoroethylene magnetite one in the reactor, then add fluoro-alkyl ether copper (I), compound R-X, sodium tert-butoxide and DMF solvent, and heated and stirred reacts 14h in the enclosed system of 80 DEG C, be cooled to room temperature, by extracted with diethyl ether 3 times, extraction liquid merges, concentrated, residue obtainedly crosses silica gel column chromatography, with ether-Skellysolve A for eluent, obtain corresponding fluoro-alkyl etherification derivative;
Described fluoro-alkyl ether copper (I), compound R-X and sodium tert-butoxide in molar ratio 1.2:1:1 add;
Every mmol fluoro-alkyl ether copper (I) uses DMF solvent 10 mL.
beneficial effect of the present invention is: the present invention with the fluoroalkyl alcohol of industrial cheapness for a kind of fluoro-alkyl ether copper (I) of Material synthesis, it can be used as the reagent of fluoro-alkyl etherificate, promote that fluoro-alkyl etherification reaction efficiently carries out, and its operation is easy, has good prospects for commercial application.
Accompanying drawing explanation
Figure
1the single crystal structure figure of fluoro-alkyl ether copper (I) title complex of 1,10-phenanthroline coordination obtained by embodiment 1.
Embodiment
More being convenient to make content of the present invention understand, below in conjunction with embodiment, technical solutions according to the invention are described further, but the present invention being not limited only to this.
embodiment
1
:
In 50mL single port flask, add a tetrafluoroethylene magnetic stir bar, and add 0.525mmol sodium tert-butoxide, 0.5mmol cuprous chloride and 25mL tetrahydrofuran solvent, mixing, under nitrogen protection, room temperature reaction 1 hour, solution filters, and obtains trimethyl carbinol cuprous solution; Add in trimethyl carbinol cuprous solution containing 1.0mmol 1, the tetrahydrofuran solution of 10-phenanthroline, after stirring at room temperature 10min, drip the tetrahydrofuran solution containing 0.5mmol trifluoroethanol, continue to stir 5min, solution filters, under vacuo except desolventizing, after gained solid washed with ether, recrystallization obtains red brown solid, be 1,10-phenanthroline and close trifluoroethyl ether copper (I) title complex.
Figure
1be the single crystal structure that 1,10-phenanthroline closes trifluoroethyl ether copper (I) title complex, its nuclear magnetic data is:
1h-NMR(400 MHz, DMSO) δ: 9.10(s, 4H), 8.64(d,
j=7.9 Hz, 4H), 8.12(s, 4H), 7.89(s, 4H) and, 3.86(s, 2H).
19F-NMR（376 MHz，DMSO）δ：-75.45（s）。
13C-NMR（101 MHz，DMSO）δ：150.23（s），144.94（s），137.08（s），129.17（s），127.28（s），124.79（s），67.45（s），25.56（s）。
embodiment
2
:
In 50mL single port flask, add a tetrafluoroethylene magnetic stir bar, and add 0.525mmol sodium tert-butoxide, 0.5mmol cuprous chloride and 25mL tetrahydrofuran solvent, mixing, under nitrogen protection, room temperature reaction 1 hour, solution filters, and obtains trimethyl carbinol cuprous solution; Add in trimethyl carbinol cuprous solution containing 1.0mmol 1, the tetrahydrofuran solution of 10-phenanthroline, after stirring at room temperature 10min, drip the tetrahydrofuran solution containing 0.5mmol C3-Fluoroalcohol, continue to stir 5min, solution filters, under vacuo except desolventizing, after gained solid washed with ether, recrystallization obtains red brown solid, be 1,10-phenanthroline and close tetrafluoro propyl ether copper (I) title complex.Its nuclear magnetic data is:
1h-NMR(400 MHz, DMSO) δ: 9.05(s, 4H), 8.62(d,
j=8.0 Hz, 4H), 8.09(s, 4H), 7.85(dd,
j=7.0,3.2 Hz, 4H), 6.43(t,
j=52.4 Hz, 1H), 3.81(s, 2H).
19F-NMR（376 MHz，DMSO）δ：-127.44（s，2F），-141.59（d，
J=52.1 Hz，2F）。
13C-NMR（101 MHz，DMSO）δ：150.28（s），144.97（s），137.19（s），129.11（s），127.26（s），124.72（s），67.45（s），31.73（s），25.55（s）。
embodiment
3
:
In 50mL single port flask, add a tetrafluoroethylene magnetic stir bar, and add 0.525mmol sodium tert-butoxide, 0.5mmol cuprous chloride and 25mL tetrahydrofuran solvent, mixing, under nitrogen protection, room temperature reaction 1 hour, solution filters, and obtains trimethyl carbinol cuprous solution; Add in trimethyl carbinol cuprous solution containing 1.0mmol 1, the tetrahydrofuran solution of 10-phenanthroline, after stirring at room temperature 10min, drip the tetrahydrofuran solution containing 0.5mmol five fluorine propyl alcohol, continue to stir 5min, solution filters, under vacuo except desolventizing, after gained solid washed with ether, recrystallization obtains red brown solid, be 1,10-phenanthroline and close five fluoropropyl ether copper (I) title complexs.Its nuclear magnetic data is:
1h-NMR(400 MHz, DMSO) δ: 9.10(s, 4H), 8.66(d,
j=8.0 Hz, 4H), 8.14(s, 4H), 7.91(s, 4H) and, 3.99(s, 2H).
19F-NMR（376 MHz，DMSO）δ：-82.12（s，3F），-124.18（s，2F）。
13C-NMR（101 MHz，CDCl
3）δ 154.97（d，
J=22.2 Hz），149.74（s），141.91（s），133.91（s），132.05（s），129.55（s），72.22（s），36.49（s），30.32（s）。
embodiment 4:
1, the 10-phenanthroline prepared by embodiment 1 closes trifluoroethyl ether copper (I), in nitrogen atmosphere, puts into tetrafluoroethylene magnetite one in the reactor, adds 0.36mmol 1,10-phenanthroline and closes trifluoroethyl ether copper (I) (phen)
2cu (OCH
2cF
3), 0.3mmol 2-bromine quinoxaline, 0.3mmol sodium tert-butoxide and 3mL N, dinethylformamide solvent, and in the enclosed system of 80 DEG C, heated and stirred reacts 12h, is cooled to room temperature, by 3 × 10mL extracted with diethyl ether, extraction liquid merges, concentrated, residue obtained silica gel column chromatography excessively, with ether: Skellysolve A=1:5 is eluent, obtains 2-trifluoro ethoxy quinoxaline, yield 92%
1h-NMR(400 MHz, CDCl
3) δ 8.60(s, 1H), 8.08(dd,
j=8.2,0.8 Hz, 1H), 7.86(dd,
j=8.3,0.9 Hz, 1H), 7.78 – 7.68(m, 1H), 7.68 – 7.54(m, 1H), 4.94(q,
j=8.4 Hz, 2H).
embodiment 5:
1, the 10-phenanthroline prepared by embodiment 1 closes trifluoroethyl ether copper (I), in nitrogen atmosphere, puts into tetrafluoroethylene magnetite one in the reactor, adds 0.36mmol 1,10-phenanthroline and closes trifluoroethyl ether copper (I) (phen)
2cu (OCH
2cF
3), the bromo-3-chloropyridine of 0.3mmol 2-, 0.3mmol sodium tert-butoxide and 3mL N, dinethylformamide solvent, and in the enclosed system of 80 DEG C, heated and stirred reacts 12h, is cooled to room temperature, by 3 × 10mL extracted with diethyl ether, extraction liquid merges, concentrated, residue obtained silica gel column chromatography excessively, is eluent with Skellysolve A, obtains 2-trifluoro ethoxy-3-chloropyridine, yield 99%
1h-NMR(400 MHz, CDCl
3) δ: 8.06(dd,
j=4.9,1.6 Hz, 1H), 7.72(dd,
j=7.7,1.6 Hz, 1H), 6.97(dd,
j=7.7,4.9 Hz, 1H), 4.85(q,
j=8.4 Hz, 2H).
embodiment 6:
1, the 10-phenanthroline prepared by embodiment 1 closes trifluoroethyl ether copper (I), in nitrogen atmosphere, puts into tetrafluoroethylene magnetite one in the reactor, adds 0.36mmol 1,10-phenanthroline and closes trifluoroethyl ether copper (I) (phen)
2cu (OCH
2cF
3), the bromo-6-cyanopyridine of 0.3mmol 2-, 0.3mmol sodium tert-butoxide and 3mL N, dinethylformamide solvent, and in the enclosed system of 80 DEG C, heated and stirred reacts 12h, is cooled to room temperature, by 3 × 10mL extracted with diethyl ether, extraction liquid merges, concentrated, residue obtained silica gel column chromatography excessively, with ether: Skellysolve A=1:3 is eluent, obtains 2-trifluoro ethoxy-6-cyanopyridine, yield 84%
1h-NMR(400 MHz, CDCl
3) δ: 7.81(dd,
j=8.5,7.3 Hz, 1H), 7.44(dd,
j=7.3,0.6 Hz, 1H), 7.14(dd,
j=8.5,0.6 Hz, 1H), 4.79(q,
j=8.4 Hz, 2H).
embodiment 7:
1, the 10-phenanthroline prepared by embodiment 2 closes 2,2,3,3-tetrafluoro propyl ether copper (I), in nitrogen atmosphere, puts into tetrafluoroethylene magnetite one in the reactor, adds 0.36mmol 1,10-phenanthroline closes 2,2,3,3-tetrafluoro propyl ether copper (I) (phen)
2cu (OCH
2cF
2cF
2h), 0.3mmol 2-bromo pyrimi piperidine, 0.3mmol sodium tert-butoxide and 3mL DMF solvent, and in the enclosed system of 80 DEG C heated and stirred reaction 12h, be cooled to room temperature, by 3 × 10mL extracted with diethyl ether, extraction liquid merges, concentrate, residue obtained silica gel column chromatography excessively, with ether: Skellysolve A=1:1 is eluent, obtain 2-(2,2,3,3-tetrafluoro propoxy-) pyrimidine, yield=94%
1h-NMR(400 MHz, CDCl
3) δ: 8.55(d,
j=4.5 Hz, 2H), 7.06(t,
j=4.4 Hz, 1H), 6.10(t,
j=53.0 Hz, 1H), 4.77(t,
j=12.2 Hz, 2H).
embodiment 8:
1, the 10-phenanthroline prepared by embodiment 2 closes 2,2,3,3-tetrafluoro propyl ether copper (I), in nitrogen atmosphere, puts into tetrafluoroethylene magnetite one in the reactor, adds 0.36mmol 1,10-phenanthroline closes 2,2,3,3-tetrafluoro propyl ether copper (I) (phen)
2cu (OCH
2cF
2cF
2h), 0.3mmol 2-bromo benzothiazole, 0.3mmol sodium tert-butoxide and 3mL DMF solvent, and in the enclosed system of 80 DEG C heated and stirred reaction 12h, be cooled to room temperature, by 3 × 10mL extracted with diethyl ether, extraction liquid merges, concentrate, residue obtained silica gel column chromatography excessively, with ether: Skellysolve A=10:1 is eluent, obtain 2-(2,2,3,3-tetrafluoro propoxy-) benzothiazole, yield 96%
1h-NMR(400 MHz, CDCl
3) δ: 7.72(dd,
j=25.0,8.0 Hz, 2H), 7.38(dt,
j=50.4,7.6 Hz, 2H), 6.05(t,
j=53.0 Hz, 1H), 5.01(t,
j=12.5 Hz, 2H).
embodiment 9:
1, the 10-phenanthroline prepared by embodiment 3 closes 2,2,3,3,3-five fluoropropyl ether copper (I), in nitrogen atmosphere, puts into tetrafluoroethylene magnetite one in the reactor, adds 0.36mmol 1,10-phenanthroline and closes 2,2,3,3,3-five fluoropropyl ether copper (I) (phen)
2cu (OCH
2cF
2cF
3), the bromo-5-nitropyridine of 0.3mmol 2-, 0.3mmol sodium tert-butoxide and 3mL DMF solvent, and in the enclosed system of 80 DEG C heated and stirred reaction 12h, be cooled to room temperature, by 3 × 10mL extracted with diethyl ether, extraction liquid merges, concentrate, residue obtained silica gel column chromatography excessively, with ether: Skellysolve A=1:5 is eluent, obtains 2-(2,2,3,3,3-five fluorine propoxy-)-5-nitropyridine, yield 89%
1h-NMR(400 MHz, CDCl
3) δ: 9.09(s, 1H), 8.47(dd,
j=9.1,2.8 Hz, 1H), 7.02(dd,
j=9.1,0.5 Hz, 1H), 4.97(t,
j=12.8 Hz, 2H).
embodiment 10:
1, the 10-phenanthroline prepared by embodiment 3 closes 2,2,3,3,3-five fluoropropyl ether copper (I), in nitrogen atmosphere, puts into tetrafluoroethylene magnetite one in the reactor, adds 0.36mmol 1,10-phenanthroline and closes 2,2,3,3,3-five fluoropropyl ether copper (I) (phen)
2cu (OCH
2cF
2cF
3), the bromo-3-chloropyridine of 0.3mmol 2-, 0.3mmol sodium tert-butoxide and 3mL DMF solvent, and in the enclosed system of 80 DEG C heated and stirred reaction 12h, be cooled to room temperature, by 3 × 10mL extracted with diethyl ether, extraction liquid merges, concentrate, residue obtained silica gel column chromatography excessively, is eluent with Skellysolve A, obtains 2-(2,2,3,3,3-five fluorine propoxy-)-3-chloropyridine, yield 85%
1h-NMR(400 MHz, CDCl
3) δ: 8.07(dd,
j=4.8,1.2 Hz, 1H), 7.72(dd,
j=7.7,1.4 Hz, 1H), 6.98(dd,
j=7.6,4.9 Hz1H), 4.91(t,
j=12.7 Hz, 2H).
The foregoing is only preferred embodiment of the present invention, all equalizations done according to the present patent application the scope of the claims change and modify, and all should belong to covering scope of the present invention.
Claims (9)
1. a fluoro-alkyl ether copper (I), is characterized in that: its structural formula is:
，
Wherein, R
ffor CF
3, CF
2cF
3, CF
2cHF
2or CF
2cF
2cF
3,
R
1and R
2independently take from H or alkyl separately.
2. fluoro-alkyl ether copper (I) according to claim 1, is characterized in that: R in the structural formula of described fluoro-alkyl ether copper (I)
1and R
2be all H.
3. fluoro-alkyl ether copper (I) according to claim 1, is characterized in that: R in the structural formula of described fluoro-alkyl ether copper (I)
1and R
2be all alkyl.
4. fluoro-alkyl ether copper (I) according to claim 1, is characterized in that: R in the structural formula of described fluoro-alkyl ether copper (I)
1for H, R
2for alkyl.
5. fluoro-alkyl ether copper (I) according to claim 1, is characterized in that: R in the structural formula of described fluoro-alkyl ether copper (I)
1and R
2independently take from H or the alkyl containing 1-4 carbon atom.
6. a preparation method for fluoro-alkyl ether copper (I) as claimed in claim 1, is characterized in that: comprise the following steps:
1) add cuprous chloride, tetrahydrofuran (THF) and sodium tert-butoxide in the reactor, stirring at room temperature reacts 1 hour under nitrogen protection, filters, obtains trimethyl carbinol cuprous solution;
2) in gained trimethyl carbinol cuprous solution, nitrogen nitrogen bitooth ligand is dripped, mixed solution at room temperature stirring reaction after 10 minutes, fluoroalkyl alcohol is dripped in mixed solution, continue stirring 20 minutes, filter, filter vacuum is except desolventizing, and after gained solid washed with ether, recrystallization obtains described fluoro-alkyl ether copper (I).
7. the preparation method of fluoro-alkyl ether copper (I) according to claim 6, is characterized in that: cuprous chloride, sodium tert-butoxide, nitrogen nitrogen bitooth ligand and fluoroalkyl alcohol in molar ratio 1:1:2:1 add; Every mmol cuprous chloride uses tetrahydrofuran (THF) 30-50 mL;
The structural formula of described nitrogen nitrogen bitooth ligand is:
，
Wherein, R
1and R
2independently take from H or alkyl separately.
8. the application of a fluoro-alkyl ether copper (I) as claimed in claim 1, it is characterized in that: at the N containing sodium tert-butoxide, in dinethylformamide solvent, described fluoro-alkyl ether copper (I) is reacted with compound R-X, generates corresponding fluoro-alkyl ether derivant;
Wherein X to be Br or I, R be in following formula a-formula aa any one:
。
9. the application of fluoro-alkyl ether copper (I) according to claim 8, it is characterized in that: its concrete operation step is: in nitrogen atmosphere, at N, fluoro-alkyl ether copper (I), compound R-X and sodium tert-butoxide is added in dinethylformamide solvent, and heated and stirred reacts 14h in the enclosed system of 80 DEG C, be cooled to room temperature, by extracted with diethyl ether 3 times, extraction liquid merges, concentrated, residue obtained silica gel column chromatography excessively, with ether-Skellysolve A for eluent, obtain corresponding fluoro-alkyl ether derivant;
Described fluoro-alkyl ether copper (I), compound R-X and sodium tert-butoxide in molar ratio 1.2:1:1 add;
Every mmol fluoro-alkyl ether copper (I) uses DMF solvent 10mL.
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510015950.6A CN104557924B (en) | 2015-01-14 | 2015-01-14 | A kind of fluoro-alkyl ether copper (I) and preparation method thereof and application |
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| WO2012007861A1 (en) * | 2010-07-12 | 2012-01-19 | Pfizer Limited | N-sulfonylbenzamide derivatives useful as voltage gated sodium channel inhibitors |
| CN102596884A (en) * | 2009-09-02 | 2012-07-18 | 纳幕尔杜邦公司 | Process for the synthesis of fluorinated ethers of aromatic acids |
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| CN102596884A (en) * | 2009-09-02 | 2012-07-18 | 纳幕尔杜邦公司 | Process for the synthesis of fluorinated ethers of aromatic acids |
| WO2012007861A1 (en) * | 2010-07-12 | 2012-01-19 | Pfizer Limited | N-sulfonylbenzamide derivatives useful as voltage gated sodium channel inhibitors |
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| Title |
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| DANIELA VULUGA, ET AL.: "Facile Access to Fluorinated Aryl and Vinyl Ethers through Copper-Catalysed Reaction of Fluoro Alcohols", 《EUR. J. ORG. CHEM.》 * |
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