CN109438322A - One kind 4 '-trifluoromethyl -3,5 '-oxazolidinyl loop coil Oxoindole compound chiral method for preparing - Google Patents
One kind 4 '-trifluoromethyl -3,5 '-oxazolidinyl loop coil Oxoindole compound chiral method for preparing Download PDFInfo
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- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/30—Indoles; Hydrogenated indoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to carbon atoms of the hetero ring
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Abstract
The present invention provides a kind of 4 '-trifluoromethyls -3, the preparation method of 5 '-oxazolidinyl loop coil Oxoindole compounds, the preparation method is that by Isatine derivatives, 2- ((2,2,2- trifluoroethyls) imino group) diethyl malonate derivative and catalyst be added reaction purification in solvent and obtain.Preparation method raw material provided by the invention is simple and easy to get, and catalyst is environmentally protective, and reaction condition is mild, and operation is easy, and synthesis step is few, and product is easy purifies and separates and can obtain high yield and excellent stereoselectivity.Simultaneous reactions are easy to amplify, and have very broad application prospect.
Description
Technical field
The invention belongs to technical field of organic synthesis, more particularly, to a kind of 4 '-trifluoromethyl -3,5 '-oxazolidinyls
The chiral method for preparing of loop coil Oxoindole compound.
Background technique
Loop coil oxindoles skeleton is widely present in many natural products and bioactivity related compound.In various loop coils
In core, oxazolidinyl loop coil oxindoles equally have many important biology, pharmaceutical properties.In addition, 3,5 '-oxazolidinyls
Spiro indole class compound has been demonstrated there is good bioactivity, such as antitumor, antibacterial activity.However, with building pyrroles
A large amount of reports of Alkylspirocyclic oxindoles enantioselective synthesis are compared, and the research of oxazolidinyl loop coil oxindoles is relatively fewer,
The catalytic enantioselective synthesis of especially 3,5 '-oxazolidinyl spiro indoles is quite few.
In recent years, fluorine scanning had been widely used for the exploitation of lead drug as conventional method.And by fluorine or containing fluorine-based
Group, which is introduced into bioactive molecule, can bring series of active effect.Due to strong electron-withdrawing ability, high electronegativity and small
Fluorine atom, introduce trifluoromethyl frequently result in molecule property significant changes.Therefore fluorine is mixed organic compound by exploitation
Methods availalbe be pharmaceutical chemical high expectations, however usually compared with single fluorination process, be selectively introducing trifluoromethyl into
The method for entering required position nevertheless suffers from many restrictions.
In view of CF3Introducing and loop coil Oxoindole skeleton important meaning, the spiral shell containing trifluoromethyl constructed at present
Ring indoles skeleton includes: spiral shell [pyrroles -3,2 '-Oxoindoles] compound, spiral shell [3,3 '-oxindole of pyrrolidines -] compound, 3,
3 '-pyrrolidinyl, two spiral shell oxindoles compound these three mother nucleus structures, and be 3 spiral shell nafoxidine alkyl structures of indoles.However
3,5 '-oxazolidinyl spiro indole asymmetric syntheses cases are less, and the indoles loop coil oxazolidine chemical combination containing chiral trifluoromethyl
The synthesis of object has no report.
Therefore developing one kind efficiently synthesizes 4 '-trifluoromethyl -3, the method for 5 '-oxazolidinyl loop coil Oxoindole compounds
With important practical significance.
Summary of the invention
It is an object of that present invention to provide a kind of 4 '-trifluoromethyl -3, the hands of 5 '-oxazolidinyl loop coil Oxoindole compounds
Property preparation method.
Above-mentioned purpose of the present invention is achieved through the following technical solutions:
The present invention provides a kind of 4 '-trifluoromethyl -3, the chiral preparation side of 5 '-oxazolidinyl loop coil Oxoindole compounds
Method, the preparation method is that by Isatine derivatives, 2- ((2,2,2- trifluoroethyl) imino group) diethyl malonate derivative and
Catalyst is added reaction purification in solvent and obtains.The reaction formula of the preparation method are as follows:
Hydroxyl, cyano, amino, nitro, halogen or phenyl；R2For hydrogen, alkyl, alkoxy, phenyl, ester group, acyl group or sulfonyl；
The R1In any one or multiple hydrogen independently by G1Replace；
G1Selected from-OH ,-NH2、-NO2, halogen, halogenated alkyl, C1-6Alkyl, C3-6Naphthenic base, C2-6Alkenyl, C2-6Alkynyl or
C6Aryl；
The R2In any one or multiple hydrogen independently by G2Replace；
G2Selected from-OH ,-NH2、-NO2, halogen, halogenated alkyl, C1-6Alkyl, C3-6Naphthenic base, C2-6Alkenyl, C2-6Alkynyl or
C6Aryl；
2- ((2,2,2- trifluoroethyl) imino group) the diethyl malonate derivant structure is
Wherein R3For hydrogen, alkyl, phenyl, R4Definition and R3It is identical；
The R3In any one or multiple hydrogen independently by G3Replace；
G3Selected from-OH ,-NH2、-NO2, halogen, halogenated alkyl, C1-6Alkyl, C3-6Naphthenic base, C2-6Alkenyl, C2-6Alkynyl or
C6Aryl；
The catalyst is difunctional small organic molecule type catalyst, bronsted alkali or Lewis base type catalyst.
Preferably, R1Selected from hydrogen, C1-C8Alkyl, alkoxy, hydroxyl, cyano, amino, nitro, halogen or substituted-phenyl；R2
Selected from hydrogen, C1-C8Alkyl, alkoxy, substituted-phenyl, ester group, acyl group or sulfonyl；R3Selected from hydrogen, C1-C8Alkyl, benzyl take
For phenyl；
The R1In any one or multiple hydrogen independently by G1Replace；
G1Selected from-OH ,-NH2、-NO2, halogen, C1-6Alkyl or C6Aryl；
The R2In any one or multiple hydrogen independently by G2Replace；
G2Selected from-OH ,-NH2、-NO2, halogen, C1-6Alkyl or C6Aryl；
The R3In any one or multiple hydrogen independently by G3Replace；
G3Selected from-OH ,-NH2、-NO2, halogen, C1-6Alkyl or C6Aryl；
Preferably, R1Selected from hydrogen, C1-C8Alkyl, C1-C6Alkoxy, hydroxyl, cyano, nitro, amino, fluorine, chlorine, bromine, iodine,
Phenyl, benzyl, N, one of N- dimethylamino；
R2Selected from hydrogen, C1-C8Alkyl, phenyl, benzyl, acetyl group, benzoyl, p-toluenesulfonyl, carbamyl, benzyl
One of oxygen carbonyl, tert-butoxycarbonyl；
R3Selected from hydrogen, C1-C8One of alkyl, substituted-phenyl, benzyl.
The preferably described catalyst be selected from triethylamine, trimethylamine, 1,8- diazabicylo, 11 carbon -7- alkene,Triethylene two Amine, potassium carbonate, sodium carbonate, sodium bicarbonate, cesium carbonate, its structural formula of difunctional organic micromolecule catalyst derived from quinine
As I-XII, the difunctional organic micromolecule catalyst XIII-XV of rosin derivative, other types of difunctional small organic molecule are urged
One or more of agent XVI-XVIII；Above-mentioned difunctional organic micromolecule catalyst structure is as follows:
Wherein difunctional organic micromolecule catalyst can get chiral 4 '-trifluoromethyl -3, the oxidation of 5 '-oxazolidinyl loop coils
Benzazolyl compounds, common bronsted alkali or lewis base can get achirality 4 '-trifluoromethyl -3,5 '-oxazolidinyl spiral shells
Epoxidation benzazolyl compounds.Preferably, the reaction temperature of the reaction is -78 DEG C -50 DEG C.
Preferably, the Isatine derivatives, 2- ((2,2,2- trifluoroethyl) imino group) diethyl malonate derivative and
The reaction molar ratio of catalyst is (1-20): (1-20): 1.
Preferably, the solvent selection methylene chloride, chloroform, 1,2- dichloroethanes, acetonitrile, methanol, ethyl alcohol, n-butanol,
One or more of isopropanol, ether, tetrahydrofuran, Isosorbide-5-Nitrae-dioxane, toluene, trimethylbenzene.
Preferably, the purification is (petroleum ether: ethyl acetate=8: 1) H60 silica gel is finally produced using column chromatography
Object.
Preferably, the reaction time of the reaction is 3-72h.
The present invention has the effect that
Preparation method raw material cheap and simple provided by the invention, catalyst is environmentally protective, and reaction condition is mild, operation letter
Just, process route is simple, and product isolates and purifies simply, and target product yield is high, and stereoselectivity is excellent, and reaction amplification is easy.
Specific embodiment
The present invention will be illustrated by the following examples, but not limited in any form to the present invention.Such as nothing
It illustrates, agents useful for same of the present invention, method and apparatus are the art conventional reagent, method and apparatus.
Unless otherwise noted, agents useful for same and material of the present invention are commercially available.
Embodiment 1:(3S, 4 ' R) 1- methyl -2- oxo -4 '-(trifluoromethyl) spiral shell [3,5 '-oxazolidine of indoline -] -
2 ', 2 '-diethyl dicarboxylate's structural formulas are as follows:
(3S, 4 ' R) 1- methyl -2- oxo -4 '-(trifluoromethyl) spiral shell [3,5 '-oxazolidine of indoline -] -2 ', 2 '-two
The chiral method for preparing of carboxylic acid diethylester:
It is taken under the conditions of -20 DEG C N-methyl-isatin 0.499g (3.1mmol), 2- ((2,2,2- trifluoroethyl) imino group) third
After diethyl adipate 1.190g (4.6mmol) and catalyst V 0.19g (10mol%) mixing, solution D CE (30.0mL) is taken to add
Enter to reaction system and is reacted.Solution is concentrated under reduced pressure after reaction 20h, residue carried out column purification (H60 silica gel, petroleum
Ether: ethyl acetate=8: 1 elution), obtain required white solid product (3S, 4 ' R) 1- methyl -2- oxo -4 '-(trifluoromethyl)
Spiral shell [3,5 '-oxazolidine of indoline -] -2 ', 2 '-diethyl dicarboxylates (1.164g, yield 90%, > 20: 1 dr and 94%
ee)。
(c=0.42, CH3OH)
High-efficient liquid phase analysis (HPLC): (chiral column Chiralcel IA-H, isopropanol/n-hexane=10/90,1.0ml/
Min, UV absorption 254nm.)tminor=6.8min, tmajor=8.0min, enantioselectivity reach 94%.
Nmr analysis:
1H NMR (400MHz, CDCl3) δ 7.60 (dd, J=7.4,0.6Hz, 1H), 7.38 (td, J=7.8,1.2Hz,
1H), 7.14 (t, J=7.2Hz, 1H), 6.82 (d, J=7.8Hz, 1H), 4.67 (d, J=13.6Hz, 1H), 4.51-4.38
(m, 2H), 4.37-4.26 (m, 3H), 3.15 (s, 3H), 1.34 (dt, J=8.8,7.1Hz, 6H)；19F NMR (376MHz,
CDCl3)δ-69.09(s)；13C NMR (101MHz, CDCl3) δ 172.82,167.43,165.26,144.64,131.33,
124.84,123.70,123.68,122.51 (q, JCF=279.6Hz), 108.87,94.32,81.25,67.66 (q, JCF=
31.3Hz), 63.28,63.07,26.43,14.07,14.04.
High resolution mass spectrum analysis:
HRMS (ESI): m/z [M+H]+calcd.for[C18H19F3N2O6]+: 417.1268, found:417.1264 ,-
0.96ppm.
Embodiment 2:(3S, 4 ' R) bromo- -4 '-(trifluoromethyl) spiral shell of 1- methyl -2- oxo [3, the 5 '-oxazole of indoline-of 5-
Alkane] -2 ', 2 '-diethyl dicarboxylate's structural formulas are as follows:
Bromo- -4 '-(trifluoromethyl) spiral shell of 1- methyl -2- oxo [3,5 '-oxazolidine of indoline -] of (3S, 4 ' R) 5- -2 ',
The chiral method for preparing of 2 '-diethyl dicarboxylates:
The bromo- 1- methylisatin 24.0mg (0.1mmol) of 5-, 2- ((2,2,2- trifluoroethyl) imido are taken under the conditions of -20 DEG C
Base) diethyl malonate 38.3mg (0.1mmol) and catalyst V 6.3mg (10mol%) mixing after, take solution D CE (1.0mL)
Reaction system is added to be reacted.Solution is concentrated under reduced pressure after reaction 10h, residue carried out column purification (H60 silica gel, stone
Oily ether: ethyl acetate=8: 1 elution), obtain the bromo- 1- methyl -2- oxo -4 '-(three of required white solid product (3S, 4 ' R) 5-
Methyl fluoride) spiral shell [3,5 '-oxazolidine of indoline -] -2 ', 2 '-diethyl dicarboxylates (47.0mg, yield 95%, 20: 1 dr of >
And 95%ee).
(c=0.28, CH3OH)
High-efficient liquid phase analysis (HPLC): (chiral column Chiralcel IA-H, isopropanol/n-hexane=10/90,0.8ml/
Min, UV absorption 254nm.)tminor=9.3min, tmajor=8.1min, enantioselectivity reach 93%.
Nmr analysis:
1H NMR (500MHz, CDCl3) δ 7.75 (s, 1H), 7.51 (d, J=8.0Hz, 1H), 6.71 (d, J=8.1Hz,
1H), 4.65 (d, J=13.6Hz, 1H), 4.50-4.38 (m, 2H), 4.37-4.25 (m, 3H), 3.14 (s, 3H), 1.40-1.29
(m, 6H)；19F NMR (471MHz, CDCl3)δ-69.01；13C NMR (126MHz, CDCl3) δ 172.33,167.24,164.99,
143.70,134.17,128.19,125.86,122.40 (q, J=279.6Hz), 116.30,110.35,94.53,80.88,
67.92 (q, J=31.5Hz), 63.39,63.24,26.57,14.08,14.04.
High resolution mass spectrum analysis:
HRMS (ESI): m/z [M+H]+calcd.for[C18H18F3N2O6Br]+: 495.0373, found:495.0363 ,-
2.02ppm.
Embodiment 4:(3S, 4 ' R) chloro- -4 '-(trifluoromethyl) spiral shell of 1- methyl -2- oxo [3, the 5 '-oxazole of indoline-of 6-
Alkane] -2 ', 2 '-diethyl dicarboxylate's structural formulas are as follows:
Isatine derivatives needed for its preparation process are the chloro- 1- methylisatin 19.6mg (0.1mmol) of 6-, other processes and reality
It is identical to apply example 2.Chloro- -4 '-(trifluoromethyl) spiral shell of 1- methyl -2- oxo [3,5 '-oxazolidine of indoline -]-of (3S, 4 ' R) 6-
2 ', 2 '-diethyl dicarboxylate's white solids (41.9mg, yield 93%, > 20: 1 dr and 95%ee).
(c=0.38, CH3OH)
High-efficient liquid phase analysis (HPLC): (chiral column Chiralcel IB-H, isopropanol/n-hexane=1/99,1.0ml/
Min, 254 nm of UV absorption.)tminor=43.8min, tmajor=15.0min, enantioselectivity reach 95%.
Nmr analysis:
1H NMR (400MHz, CDCl3) δ 7.54 (d, J=8.0Hz, 1H), 7.11 (dd, J=8.0,1.7Hz, 1H), 6.83
(d, J=1.7Hz, 1H), 4.64 (d, J=13.7Hz, 1H), 4.51-4.37 (m, 2H), 4.36-4.23 (m, 3H), 3.13 (s,
3H), 1.33 (dd, J=13.5,7.1Hz, 6H)；19F NMR (376MHz, CDCl3)δ-69.06；13C NMR (101MHz,
CDCl3) δ 172.77,167.31,165.05,145.79,137.32,125.93,123.58,122.42 (q, J=
279.4Hz), 122.21,109.75,94.39,80.81,67.71 (q, J=31.5Hz), 63.37,63.15,26.57,
14.06 14.04.
High resolution mass spectrum analysis:
HRMS (ESI): m/z [M+H]+calcd.for[C18H18F3N2O6Cl]+: 451.0878, found:451.0873 ,-
1.11ppm.
Embodiment 4:(3S, 4 ' R) fluoro- -4 '-(trifluoromethyl) spiral shell of 1- methyl -2- oxo [3, the 5 '-oxazole of indoline-of 7-
Alkane] -2 ', 2 '-diethyl dicarboxylate's structural formulas are as follows:
Isatine derivatives needed for its preparation process are the fluoro- 1- methylisatin 17.9mg (0.1mmol) of 7-, other processes and reality
It is identical to apply example 2.Fluoro- -4 '-(trifluoromethyl) spiral shell of 1- methyl -2- oxo [3,5 '-oxazolidine of indoline -]-of (3S, 4 ' R) 7-
2 ', 2 '-diethyl dicarboxylate's white solids (40.0mg, yield 93%, > 20: 1 dr and 96%ee).
(c=0.32, CH3OH)
High-efficient liquid phase analysis (HPLC): (chiral column Chiralcel IB-H, isopropanol/n-hexane=5/95,1.0ml/
Min, 220 nm of UV absorption.)tminor=11.1min, tmajor=6.2min, enantioselectivity reach 96%.
Nmr analysis:
1H NMR (400MHz, CDCl3) δ 7.43 (dd, J=6.9,1.4Hz, 1H), 7.15-7.04 (m, 2H), 4.67 (d, J
=13.7 Hz, 1H), 4.51-4.38 (m, 2H), 4.38-4.24 (m, 3H), 3.36 (d, J=2.6Hz, 3H), 1.34 (dd, J=
13.5,7.0 Hz, 6H)；19F NMR (376MHz, CDCl3) δ -69.08, -135.67；13C NMR (101MHz, CDCl3)δ
172.54,167.32,165.09,147.78 (d, J=244.9Hz), 131.12 (d, J=9.1Hz), 126.62 (d, J=
3.2Hz), 124.42 (d, J=6.3Hz), 122.42 (q, J=280.5Hz), 120.82 (d, J=3.2Hz), 119.40 (d, J
=19.2Hz), 94.46,81.00,68.03 (q, J=31.6Hz), 63.37,63.15,29.03 (d, J=5.5Hz),
14.07.
High resolution mass spectrum analysis:
HRMS (ESI): m/z [M+H]+calcd.for[C18H18F4N2O6]+: 435.1174, found:435.1172 ,-
0.46ppm.
Embodiment 5:(3S, 4 ' R) 1- benzyl -2- oxo -4 '-(trifluoromethyl) spiral shell [3,5 '-oxazolidine of indoline -] -
2 ', 2 '-diethyl dicarboxylate's structural formulas are as follows:
Isatine derivatives needed for its preparation process are 1- benzyl isatin 23.7mg (0.1mmol), other processes and embodiment 2
It is identical.(3S, 4 ' R) 1- benzyl -2- oxo -4 '-(trifluoromethyl) spiral shell [3,5 '-oxazolidine of indoline -] -2 ', 2 '-dicarboxyls
Diethyl phthalate white solid (45.1mg, yield 92%, > 20: 1 dr and 96%ee).
(c=0.43, CH3OH)
High-efficient liquid phase analysis (HPLC): (chiral column Chiralcel IB-H, isopropanol/n-hexane=5/95,1.0ml/
Min, 220 nm of UV absorption.)tminor=10.5min, tmajor=8.6min, enantioselectivity reach 96%.
Nmr analysis:
1H NMR (500MHz, CDCl3) δ 7.61 (d, J=6.8Hz, 1H), 7.30 (d, J=6.0Hz, 2H), 7.26 (s,
4H), 7.10 (t, J=6.6Hz, 1H), 6.68 (d, J=7.3Hz, 1H), 5.05 (d, J=15.7Hz, 1H), 4.73 (d, J=
13.6Hz, 1H), 4.61 (d, J=15.6Hz, 1H), 4.52-4.28 (m, 5H), 1.35 (dd, J=14.5,7.1Hz, 6H)
19F NMR (471MHz, CDCl3)δ-68.75.
13C NMR (126MHz, CDCl3) δ 172.99,167.43,165.30,143.90,135.10,131.26,
128.93,127.92,127.37,124.92,123.71,122.40 (q, J=330.4Hz), 110.02,94.38,81.28,
67.69 (q, J=31.4Hz), 63.31,63.10,44.23,14.09,14.07.
High resolution mass spectrum analysis:
HRMS (ESI): m/z [M+H]+calcd.for[C24H23F3N2O6]+: 493.1581, found:493.1572 ,-
1.82ppm.
Claims (9)
1. one kind 4 '-trifluoromethyl -3, the chiral method for preparing of 5 '-oxazolidinyl loop coil Oxoindole compounds, feature exist
In, the preparation method is that by Isatine derivatives, 2- ((2,2,2- trifluoroethyl) imino group) diethyl malonate derivative and
Catalyst is added reaction purification in solvent and obtains；The reaction formula of the preparation method are as follows:
Hydroxyl, cyano, amino, nitro, halogen or phenyl；R2For hydrogen, alkyl, alkoxy, phenyl, ester group, acyl group or sulfonyl；
The R1In any one or multiple hydrogen independently by G1Replace；
G1Selected from-OH ,-NH2、-NO2, halogen, halogenated alkyl, C1-6Alkyl, C3-6Naphthenic base, C2-6Alkenyl, C2-6Alkynyl or C6Virtue
Base；
The R2In any one or multiple hydrogen independently by G2Replace；
G2Selected from-OH ,-NH2、-NO2, halogen, halogenated alkyl, C1-6Alkyl, C3-6Naphthenic base, C2-6Alkenyl, C2-6Alkynyl or C6Virtue
Base；
2- ((2,2,2- trifluoroethyl) imino group) the diethyl malonate derivant structure isWherein R3
For hydrogen, alkyl, phenyl, R4Definition and R3It is identical；
The R3In any one or multiple hydrogen independently by G3Replace；
G3Selected from-OH ,-NH2、-NO2, halogen, halogenated alkyl, C1-6Alkyl, C3-6Naphthenic base, C2-6Alkenyl, C2-6Alkynyl or C6Virtue
Base；
The catalyst is difunctional small organic molecule type catalyst, bronsted alkali or Lewis base type catalyst.
2. 4 '-trifluoromethyl -3 according to claim 1, the chiral system of 5 '-oxazolidinyl loop coil Oxoindole compounds
Preparation Method, which is characterized in that R1Selected from hydrogen, C1-C8Alkyl, alkoxy, hydroxyl, cyano, amino, nitro, halogen or substituted benzene
Base；R2Selected from hydrogen, C1-C8Alkyl, alkoxy, substituted-phenyl, ester group, acyl group or sulfonyl；R3Selected from hydrogen, C1-C8Alkyl, benzyl
Or substituted-phenyl；
The R1In any one or multiple hydrogen independently by G1Replace；
G1Selected from-OH ,-NH2、-NO2, halogen, C1-6Alkyl or C6Aryl；
The R2In any one or multiple hydrogen independently by G2Replace；
G2Selected from-OH ,-NH2、-NO2, halogen, C1-6Alkyl or C6Aryl；
The R3In any one or multiple hydrogen independently by G3Replace；
G3Selected from-OH ,-NH2、-NO2, halogen, C1-6Alkyl or C6Aryl.
3. 4 '-trifluoromethyl -3 according to claim 1, the chiral system of 5 '-oxazolidinyl loop coil Oxoindole compounds
Preparation Method, which is characterized in that R1Selected from hydrogen, C1-C8Alkyl, C1-C6Alkoxy, hydroxyl, cyano, nitro, amino, fluorine, chlorine, bromine,
Iodine, phenyl, benzyl, N, one of N- dimethylamino；
R2Selected from hydrogen, C1-C8Alkyl, phenyl, benzyl, acetyl group, benzoyl, p-toluenesulfonyl, carbamyl, benzyloxy carbonyl
One of base, tert-butoxycarbonyl；
R3Selected from hydrogen, C1-C8One of alkyl, substituted-phenyl, benzyl.
4. 4 '-trifluoromethyl -3 according to claim 1, the chiral system of 5 '-oxazolidinyl loop coil Oxoindole compounds
Preparation Method, which is characterized in that the catalyst be selected from triethylamine, trimethylamine, 1,8- diazabicylo, 11 carbon -7- alkene,Three second Alkene diamines, potassium carbonate, sodium carbonate, sodium bicarbonate, cesium carbonate, difunctional organic micromolecule catalyst derived from quinine its knot
It is the difunctional organic micromolecule catalyst XIII-XV of structure formula such as I-XII, rosin derivative, difunctional organic small point other types of
One or more of muonic catalysis agent XVI-XVIII；Above-mentioned difunctional organic micromolecule catalyst structure is as follows:
Wherein difunctional organic micromolecule catalyst can get chiral 4 '-trifluoromethyl -3,5 '-oxazolidinyl loop coil Oxoindoles
Compound, common bronsted alkali or lewis base can get achirality 4 '-trifluoromethyl -3,5 '-oxazolidinyl loop coil oxygen
Change benzazolyl compounds.
5. 4 '-trifluoromethyl -3 according to claim 1, the chiral system of 5 '-oxazolidinyl loop coil Oxoindole compounds
Preparation Method, which is characterized in that the reaction temperature of the reaction is -78 DEG C -50 DEG C.
6. 4 '-trifluoromethyl -3 according to claim 1, the chiral system of 5 '-oxazolidinyl loop coil Oxoindole compounds
Preparation Method, which is characterized in that the Isatine derivatives, 2- ((2,2,2- trifluoroethyl) imino group) diethyl malonate derivative
Reaction molar ratio with catalyst is (1-20): (1-20): 1.
7. 4 '-trifluoromethyl -3 according to claim 1, the chiral system of 5 '-oxazolidinyl loop coil Oxoindole compounds
Preparation Method, which is characterized in that the solvent selection methylene chloride, chloroform, 1,2- dichloroethanes, acetonitrile, methanol, ethyl alcohol, positive fourth
One or more of alcohol, isopropanol, ether, tetrahydrofuran, Isosorbide-5-Nitrae-dioxane, toluene, trimethylbenzene.
8. 4 '-trifluoromethyl -3 according to claim 1, the chiral system of 5 '-oxazolidinyl loop coil Oxoindole compounds
Preparation Method, which is characterized in that the purification is (petroleum ether: ethyl acetate=8: 1) H60 silica gel obtains final using column chromatography
Product.
9. 4 '-trifluoromethyl -3 according to claim 1, the chiral system of 5 '-oxazolidinyl loop coil Oxoindole compounds
Preparation Method, which is characterized in that the reaction time is 3-72h.
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111303188A (en) * | 2020-04-08 | 2020-06-19 | 东莞暨南大学研究院 | Novel oxoindole spiro-compound and preparation method thereof |
| CN116478181A (en) * | 2023-02-16 | 2023-07-25 | 中国海洋大学 | Catalytic synthesis method of chiral oxazoline compound |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| IL105042A (en) * | 1992-03-14 | 2000-07-16 | Hoechst Ag | Substituted pyrimidines processes for their preparation pharmaceutical compositions containing them and their use as insecticides acaricides nematocides and fungicides |
| CN102510721A (en) * | 2009-07-16 | 2012-06-20 | 拜尔农作物科学股份公司 | Synergistic active substance combinations containing phenyl triazoles |
-
2018
- 2018-11-19 CN CN201811380512.XA patent/CN109438322A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| IL105042A (en) * | 1992-03-14 | 2000-07-16 | Hoechst Ag | Substituted pyrimidines processes for their preparation pharmaceutical compositions containing them and their use as insecticides acaricides nematocides and fungicides |
| CN102510721A (en) * | 2009-07-16 | 2012-06-20 | 拜尔农作物科学股份公司 | Synergistic active substance combinations containing phenyl triazoles |
Non-Patent Citations (2)
| Title |
|---|
| JINHUAN SU，等: "Asymmetric Synthesis of 2’-Trifluoromethylated Spiro-pyrrolidine-3,3’-oxindoles via Squaramide-Catalyzed Umpolung and 1,3-Dipolar Cycloaddition", 《ADV. SYNTH. CATAL.》 * |
| 朱文岐 等: "4’-三氟甲基-3,2’-吡咯烷基双螺环氧化吲哚化合物的合成与表征", 《井冈山大学学报(自然科学版)》 * |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111303188A (en) * | 2020-04-08 | 2020-06-19 | 东莞暨南大学研究院 | Novel oxoindole spiro-compound and preparation method thereof |
| CN111303188B (en) * | 2020-04-08 | 2021-07-30 | 东莞暨南大学研究院 | Oxoindole spiro-compound and preparation method thereof |
| CN116478181A (en) * | 2023-02-16 | 2023-07-25 | 中国海洋大学 | Catalytic synthesis method of chiral oxazoline compound |
| CN116478181B (en) * | 2023-02-16 | 2024-05-17 | 中国海洋大学 | Catalytic synthesis method of chiral oxazoline compound |
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