CN103709072B - Optically active trifluoromethyl amine compound and preparation method thereof - Google Patents

Optically active trifluoromethyl amine compound and preparation method thereof Download PDF

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CN103709072B
CN103709072B CN201210370749.6A CN201210370749A CN103709072B CN 103709072 B CN103709072 B CN 103709072B CN 201210370749 A CN201210370749 A CN 201210370749A CN 103709072 B CN103709072 B CN 103709072B
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trifluoromethyl
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methyl
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CN103709072A (en
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史一安
刘懋
李静
肖晓
谢颖
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Institute of Chemistry CAS
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Abstract

The invention discloses an optically active trifluoromethyl amine compound and a preparation method thereof. The preparation method of the trifluoromethyl aldimine compound shown as a formula V comprises the following steps of (1) reacting 2-chloro-4-cyanobenzylamine with a trifluoromethyl ketone shown as a formula II under the catalysis of an acidic catalyst to obtain trifluoromethyl ketimine shown as a formula III; and (2) carrying out a transamination reaction on the trifluoromethyl ketimine shown as the formula III under the catalysis of a chiral alkali catalyst derived from cinchona alkaloid shown as a formula IV to obtain the trifluoromethyl aldimine shown as the formula V. A preparation method for the trifluoromethyl amine shown as a formula I comprises the following step of subjecting the trifluoromethyl aldimine compound shown as the formula V to a hydrolysis reaction under an acid condition. Both the trifluoromethyl imine compounds and the trifluoromethyl amine compounds provided by the invention are important structural units of important drug intermediates.

Description

A kind of photolytic activity trifluoromethyl amine compound and preparation method thereof
Technical field
The present invention relates to a kind of photolytic activity trifluoromethyl amine compound and preparation method thereof.
Background technology
Due to the physical properties that trifluoromethyl amine compound is special, make photolytic activity trifluoromethyl amine have important using value in the field such as medical, agriculture, a lot of pharmaceutical activity molecule is all derive from photolytic activity trifluoromethyl amine.Trifluoromethyl amine can be obtained through simple hydrolysis by trifluoromethyl aldimine.
The method preparing optically active amine at present in organic synthesis mainly contains the catalytic hydrogenation of trifluoromethyl imines, and these methods need to use noble metal mostly, and the condition of the nucleophilic addition(Adn) of trifluoromethyl imines is harsh, needs absolute.
Summary of the invention
The object of this invention is to provide a kind of photolytic activity trifluoromethyl amine compound and preparation method thereof, the substrate spectrum of the method is wide, reaction conditions is gentle, easy and simple to handle, productive rate is high, enantiomer is excessive can up to 94%, be a kind of method with industrial production potential, trifluoromethyl aldimine provided by the invention is a kind of important organic synthesis intermediate.
Trifluoromethyl aldimine shown in formula V provided by the present invention,
In formula V, R is selected from methyl, ethyl, n-propyl, normal-butyl, methylcyclohexyl, CH 3xCH 2cH 2cH 2, R 1cH=CHCH 2cH 2, R 1c ≡ CCH 2cH 2and ArCH 2cH 2in any one, wherein, X is selected from any one in Sauerstoffatom, sulphur atom and nitrogen-atoms, R 1be selected from any one in hydrogen atom, methyl, ethyl, phenyl and benzyl; Ar is selected from any one in thiophene, naphthyl and substituted-phenyl, and described substituted-phenyl is that ortho position, contraposition or a position are by the phenyl that in methyl, methoxyl group, nitro, cyano group, benzyloxy, fluorine atom, chlorine atom and bromine atoms, any one replaces.
Shown in formula V provided by the invention, the preparation method of trifluoromethyl aldimine, comprises the steps:
(1) trifluorumethylketone shown in 2-chloro-4-cyano group benzylamine and formula II carries out being obtained by reacting the ketoimine of trifluoromethyl shown in formula III under the catalysis of an acidic catalyst;
In formula II and formula III, R is selected from methyl, ethyl, n-propyl, normal-butyl, methylcyclohexyl, CH 3xCH 2cH 2cH 2, R 1cH=CHCH 2cH 2, R 1c tri-CCH 2cH 2and ArCH 2cH 2in any one, wherein, X is selected from any one in Sauerstoffatom, sulphur atom and nitrogen-atoms, R 1be selected from any one in hydrogen atom, methyl, ethyl, phenyl and benzyl; Ar is selected from any one in thiophene, naphthyl and substituted-phenyl, and described substituted-phenyl is that ortho position, contraposition or a position are by the phenyl that in methyl, methoxyl group, nitro, cyano group, benzyloxy, fluorine atom, chlorine atom and bromine atoms, any one replaces;
(2) carry out turning aminating reaction under the catalysis of chiral base catalyzer that the ketoimine of trifluoromethyl shown in formula III derives at quinine shown in formula IV and obtain the aldimine of trifluoromethyl shown in formula V;
In formula IV, R 3be selected from any one in hydrogen atom, methyl, ethyl, n-propyl, allyl group, normal-butyl, benzoyl, ethanoyl and phenyl; R 4be selected from any one in ethyl and vinyl; Ar ' is phenyl or substituted-phenyl.
In above-mentioned preparation method, described in step (1), the solvent of reaction is any one in benzene,toluene,xylene, trimethylbenzene, bromobenzene chloroform and acetonitrile; The temperature of described reaction is 50 ~ 130 DEG C, specifically can be 50 DEG C, 80 DEG C or 130 DEG C, and the time is 3 ~ 24 hours, specifically can be 3 hours, 5 hours or 24 hours.
In above-mentioned preparation method, in step (1), 2-chloro-4-cyano group benzylamine is (1 ~ 3) with the molfraction ratio of trifluorumethylketone shown in formula II: 1, specifically can be (1 ~ 1.6): 1,1.2: 1,1.5: 1,1.52: 1 or 1.6: 1.
In above-mentioned preparation method, in step (2), described in turn aminating reaction solvent be benzene,toluene,xylene, trimethylbenzene, bromobenzene, ethyl acetate, tetrahydrofuran (THF) or acetonitrile; The described temperature turning aminating reaction is 0 ~ 50 DEG C, specifically can be 0 DEG C, 20 DEG C, 35 DEG C or 50 DEG C, and the time is 24 ~ 108h, specifically can be 24 hours, 72 hours or 108 hours.
In above-mentioned preparation method, in step (2), the chiral base catalyzer that quinine shown in formula IV derives is (1 ~ 3) with the molfraction ratio of the ketoimine of trifluoromethyl shown in formula III: 10, as 1: 10.
Trifluoromethyl amine shown in formula I provided by the invention,
In formula I, R is selected from methyl, ethyl, n-propyl, normal-butyl, methylcyclohexyl, CH 3xCH 2cH 2cH 2, R 1cH=CHCH 2cH 2, R 1c ≡ CCH 2cH 2and ArCH 2cH 2in any one, wherein, X is selected from any one in Sauerstoffatom, sulphur atom and nitrogen-atoms, R 1to wash in hydrogen atom, methyl, ethyl, phenyl and benzyl any one; Ar is selected from any one in thiophene, naphthyl and substituted-phenyl, and described substituted-phenyl is that ortho position, contraposition or a position are by the phenyl that in methyl, methoxyl group, nitro, cyano group, benzyloxy, fluorine atom, chlorine atom and bromine atoms, any one replaces;
In formula I, the C atom of * mark is chiral carbon.
Present invention also offers the preparation method of trifluoromethyl amine shown in formula I, comprise the steps:
Namely the aldimine of trifluoromethyl shown in formula V obtains trifluoromethyl amine shown in formula I through hydrolysis reaction in acid condition.
In above-mentioned preparation method, the solvent of described hydrolysis reaction can be tetrahydrofuran (THF), ether, toluene, methyl alcohol, ethanol or ethylene glycol;
Described hydrolysis reaction carries out under the condition of dilute hydrochloric acid, and the volumetric molar concentration of described dilute hydrochloric acid can be 0.5 ~ 6.0 mol/L, as 6.0 mol/L.
In above-mentioned preparation method, the temperature of described hydrolysis reaction is 4 ~ 30 DEG C, and the time is 1 ~ 24 hour, as reacted 4 hours at 20 DEG C;
Described method also comprises and to extract described trifluoromethyl amine and the step of column chromatography for separation, as with normal hexane and ether for eluent carries out column chromatography.
Preparation method provided by the invention, with the trifluorumethylketone of different structure for substrate, adopts first synthesizing imine, take chiral base as catalyzer, through turning amination, then through hydrolysis, final high yield, high enantioselectivity obtains the method for trifluoromethyl amine, the method mild condition, substrate use range is wide, and productive rate is high, enantiomer is excessive up to 94%, can have larger industrialization potential.Trifluoromethyl imine compound provided by the present invention and trifluoromethyl amine compound are all important feature unit of the important pharmaceutical intermediate of a class, as it prepares 2-trifluoromethyl Tetrahydroquinolinesas by ripe organic synthesis types such as linked reactions, so it has important using value in synthesis 2-trifluoromethyl Tetrahydroquinolinesas.
Embodiment
The experimental technique used in following embodiment if no special instructions, is ordinary method.
Material used in following embodiment, reagent etc., if no special instructions, all can obtain from commercial channels.
The preparation method of 2-used in following embodiment chloro-4-cyano group benzylamine is as follows: a dry 1L there-necked flask is vacuumized logical nitrogen three times, after add 2-chloro-4-cyano group toluene (30g, 198mmol), NBS (42.4g, 238mmol), AIBN (3.27g, 20mmol) tetracol phenixin (700mL), spend the night in 90 DEG C of return stirrings, reaction solution cooled and filtered is spin-dried for rear column chromatography (eluent is petrol ether/ethyl acetate=60/1-40/1), products therefrom is spin-dried for and obtains 23.2g2-chloro-4-cyano group benzyl bromine, reclaim raw material 11.4g, productive rate 82%.
By chloro-for 2-4-cyano group benzyl bromine (10g, 43.4mmol) with HMTA (6.08g, 43.4mmol) be dissolved in 400mL ethanol, in stirred overnight at room temperature, ethanol inclined after, add ethanol (372mL), ethanol, after 2 hours, is spin-dried for by concentrated hydrochloric acid (24.8mL) return stirring, after adding the water of 100mL, after ethyl acetate (2*30mL) washing, by aqueous phase Na 2cO 3after solid regulates pH to 10, rear column chromatography (eluent is ethyl acetate/methanol/triethylamine=50/1/1) is spin-dried for carrying out drying after chloroform (3*50mL) extraction, products therefrom is spin-dried for and obtains 6.2g light yellow solid 2-chloro-4-cyano group benzylamine, productive rate 85%.
Shown in formula IV-a used in following embodiment, compound is prepared by the following method:
Quinine (10.18g, 31.4mmol) is dissolved in dry DMF (80mL), adds NaH (70% is dispersed in oil) (3.23g, 94.2mmol) under a nitrogen atmosphere in batches.After reaction solution stirs one hour, bromo-derivative shown in formula 4 is dissolved in DMF (20mL), be added drop-wise in above-mentioned solution, after adding after 40 degree of stirrings are spent the night that saturated aqueous common salt is overworked and going out with after ethyl acetate (3*200mL) extraction by brine It organic phase after use MgSO 4be spin-dried for after drying.
By NaH (70% is dispersed in oil) (5.38g, 157.0mmol, washed with normal hexane) be dissolved in DMF (122mL), for suspension, by EtSH (19.82g, 314mmol) be added drop-wise in above-mentioned suspension, after dripping, stir after 20 minutes, the liquid that upper step obtains is dissolved in DMF (60mL), be added drop-wise in above-mentioned solution, after 110 degree of stirrings are spent the night, dilute with salt solution after adding 4N HCl, after ethyl acetate (3X200mL) extraction, after organic phase regulates pH to 10 with strong aqua, with brine It, MgSO 4dry, be spin-dried for rear column chromatography and obtain product shown in formula 1.
Product shown in formula 1 (27.0mmol) is dissolved in chloroform (200mL), adds PhNTf 2(11.56g, 32.5mmol), Et 3n (6.28g, 62.1mmol), is placed in stirred overnight at room temperature.After 2N HCl (2*40mL) washing, after saturated aqueous sodium carbonate (2*40mL) washing, MgSO 4be spin-dried for column chromatography after drying and obtain product shown in formula 2.
By amine (25.77mmol) shown in product shown in formula 2 (21.48mmol), formula 5, Pd (OAc) 2(0.241g, 1.07mmol), BINAP (1.070g, 1.72mmol) and Cs 2cO 3(9.798g, 30.07mmol) joins in reactor, after vacuumizing logical nitrogen three times, adds toluene (210mL), backflow stirred overnight.Be spin-dried for after reaction solution diatomite filtration, column chromatography obtains compound shown in formula IV-a.
The reaction equation of said process is:
The structural identification result of compound shown in formula IV-a is as follows: 1h NMR (400MHz, CDCl 3) δ 8.69 (d, J=4.8Hz, 1H), 8.14 (s, 2H), 7.98 (d, J=9.2Hz, 1H), 7.43 (d, J=2.8Hz, 1H), 7.06-6.96 (m, 4H), 5.77-5.65 (m, 2H), 5.06-4.87 (m, 3H), 3.51-3.12 (m, 7H), 3.08-2.70 (m, 5H), 2.70-2.57 (m, 1H), 2.57-2.46 (m, 1H), 2.30-2.20 (m, 1H), 1.92-1.68 (m, 5H), 1.58-1.44 (m, 2H), 1.30-1.15 (m, 30H); 13c NMR (100MHz, CDCl 3) δ 148.9,147.1,147.0,146.5,146.4,145.1 144.7,144.0,142.0,141.6,133.1,132.0,128.1,121.1,119.9,119.4,118.6,114.3,102.8,80.9,69.7,60.3,57.2,43.3,40.2,34.2,32.6,29.3,29.0,28.1,27.9,24.9,24.7,24.6,24.2,23.8,23.4,21.7.
Embodiment 1, synthesis 1,1,1-tri-fluoro-2-enanthaldehyde imines (see structural formula V-a)
(1) in reactor, add 2-chloro-4-cyano group benzylamine (500mg successively, 3mmol) and 4A molecular sieve (1.2g), after vacuumizing logical nitrogen three times, chloroform (7.0mL) is added, acetic acid (262mg, 4.4mmol) stirs 20 minutes.Add 1,1, fluoro-2-heptanone (the 421mg of 1-tri-, the oil bath return stirring of 80 DEG C is put into 2.5mmol), react and after 5 hours, reactor is taken out from oil bath, with being spin-dried for column chromatography (eluent is normal hexane: ether=15/1) after diatomite filtration, obtain 692mg yellow solid trifluoromethyl ketoimine (shown in formula III-a), yield is 85%.
Structural identification result is as follows: 1h NMR (400MHz, CDCl 3) δ 7.72 (d, J=8.0Hz, 1H), 7.68 (d, J=1.2Hz, 1H), 7.58 (dd, J=8.0,1.2Hz, 1H), 4.76 (s, 2H), 2.60-2.45 (m, 2H), 1.65-1.50 (m, 2H), 1.45-1.27 (m, 4H), 0.91 (t, J=7.2Hz, 3H); 13c NMR (100MHz, CDCl 3) δ 163.0 (q, J c-F=3.4Hz), 141.9,133.8,132.6,130.9,130.0,120.1 (q, J c-F=272Hz), 117.7,112.6,51.7,32.0,28.2,25.7,22.3,13.7.
(2) in reactor, 1 is added successively, the fluoro-2-heptanone imines of 1,1-tri-(shown in formula III-a) (158.1mg, 0.5mmol), chiral base (shown in formula IV-a) (37.9mg, 0.05mmol) and 0.5mL benzene.Reactor is put into 35 DEG C of stirrings, by reaction solution column chromatography (eluent is normal hexane: ether=20/1) after 72 hours, obtain 150.2mg colourless liquid aldimine (shown in formula V-a), yield 95%.It is 93% that HPLC records enantiomeric excess numerical value.
HPLC condition: chirality AS-H post, moving phase: the volume ratio of normal hexane and Virahol is the mixed solvent of 95: 5, flow velocity: 0.5mL/min, absorbing wavelength: 214nm.
Structural identification result is as follows: 1h NMR (400MHz, CDCl 3) δ 8.70 (s, 1H), 8.20 (d, J=8.4Hz, 1H), 7.69 (s, 1H), 7.59 (d, J=8.0Hz, 1H), 3.79-3.67 (m, 1H), 1.96-1.79 (m, 2H), 1.37-1.15 (m, 6H), 0.86 (t, J=6.4Hz, 3H); 13c NMR (100MHz, CDCl 3) δ 160.4,136.5,136.1,133.4,130.6,129.7,125.3 (q, J c-F=279.0Hz), 117.1,116.0,72.1 (q, J c-F=28.0Hz), 31.3,28.8,25.0,22.5,14.0.
Embodiment 2, synthesis 1,1,1-tri-fluoro-5-methoxyl group-2-enanthaldehyde imines (formula V-b)
(1) in reactor, add 2-chloro-4-cyano group benzylamine (625mg successively, 3.8mmol) and 4A molecular sieve (1.2g), after vacuumizing logical nitrogen three times, chloroform (7.0mL) is added, acetic acid (338mg, 5.6mmol) stirs 20 minutes.Add 1,1, the fluoro-5-methoxyl group-2-heptanone (425mg of 1-tri-, the oil bath return stirring of 50 DEG C is put into 2.5mmol), react and after 24 hours, reactor is taken out from oil bath, obtain 701mg faint yellow solid trifluoromethyl ketoimine (shown in formula III-b) with being spin-dried for after filtered through silica gel, yield is 88%.
Structural identification result is as follows: 1h NMR (400MHZ, CDCl 3) δ 7.71 (d, J=8.0Hz, 1H), 7.66 (s, 1H), 7.58 (d, J=8.4Hz, 1H), 4.81 (s, 2H), 3.40 (t, J=7.2Hz, 2H), 3.32 (s, 3H), 2.67 (t, J=8.0Hz, 2H), 1.98-1.82 (m, 2H); 13c NMR (100MHz, CDCl 3) δ 162.3 (q, J c-F=3.2Hz), 142.0,133.8,132.4,130.8,129.8,119.9 (q, J c-F=278Hz), 117.6,112.4,71.1,58.7,51.7,26.1,24.8.
(2) in reactor, 1 is added successively, the fluoro-5-methoxyl group-2-heptanone imines of 1,1-tri-(shown in formula III-b) (159.4mg, 0.5mmol), chiral base (shown in formula IV-a) (37.9mg, 0.05mmol) and 0.5mL benzene.Reactor is put into 0 DEG C of stirring, by reaction solution column chromatography (eluent is normal hexane: ether=8/1) after 108 hours, obtain 147.6mg colourless liquid aldimine (shown in formula V-b), yield 93%.It is 86% that HPLC records enantiomeric excess numerical value.
HPLC condition: chirality AS-H post, moving phase: the volume ratio of normal hexane and Virahol is the mixed solvent of 95: 5, flow velocity: 0.5mL/min, absorbing wavelength: 214nm.
Structural identification result is as follows: 1h NMR (400MHz, CDCl 3) δ 8.73 (s, 1H), 8.22 (d, J=8.0Hz, 1H), 7.71 (d, J=1.2Hz, 1H), 7.60 (d, J=8.0Hz, 1H), 3.87-3.76 (m, 1H), 3.46-3.36 (m, 2H), 3.32 (s, 3H), 2.09-1.88 (m, 2H), 1.58-1.46 (m, 2H); 13c NMR (100MHz, CDCl 3) δ 160.9,136.5,136.2,133.5,130.6,129.7,125.2 (q, J c-F=279.0Hz), 117.2,116.1,72.20,71.9 (q, J c-F=28.0Hz), 58.8,26.2,25.6.
Embodiment 3, (R)-1,1,1-tri-fluoro-4-p-methylphenyl-2-butyraldehyde imines (see structural formula V-c)
(1) in reactor, add 2-chloro-4-cyano group benzylamine (399.9mg successively, 1.8mmol) and 4A molecular sieve (650mg), after vacuumizing logical nitrogen three times, add chloroform (4.5mL), acetic acid (108.1mg, 1.8mmol) stirs 20 minutes.Add 1,1, the fluoro-4-p-methylphenyl-2-butanone (324.3mg of 1-tri-, the oil bath return stirring of 130 DEG C is put into 1.5mmol), react and after 3 hours, reactor is taken out from oil bath, with being spin-dried for column chromatography (eluent is normal hexane: methylene dichloride=4/3) after diatomite filtration, in normal hexane, recrystallization obtains 427.0mg colorless solid trifluoromethyl ketoimine (shown in formula III-c), and yield is 78%.
Structural identification result is as follows: 1h NMR (400MHz, CDCl 3) δ 7.60 (s, 1H), 7.58-7.48 (m, 2H), 7.12-7.02 (m, 4H), 4.34 (s, 2H), 2.97-2.81 (m, 4H), 2.27 (s, 3H); 13c NMR (100MHz, CDCl 3) δ 161.2 (q, J c-F=3.2Hz), 141.9,136.6,136.2,133.6,132.3,130.7,129.7,128.44,128.36,120.0 (q, J c-F=278Hz), 117.6,112.2,51.7,31.9,30.2,21.1.
(2) in reactor, 1 is added successively, the fluoro-4-p-methylphenyl-2-butanone imines of 1,1-tri-(shown in formula III-c) (182.4mg, 0.5mmol), chiral base (shown in formula IV-a) (37.9mg, 0.05mmol) and 0.5mL benzene.Reactor is put into 20 DEG C of stirrings, by reaction solution column chromatography (eluent is sherwood oil: ether=15/1) after 72 hours, obtain 180.6mg colourless liquid aldimine (shown in formula V-c), yield 99%.It is 94% that HPLC records enantiomeric excess numerical value.
HPLC condition: chirality AD-H post, moving phase: the volume ratio of normal hexane and Virahol is the mixed solvent of 95: 5, flow velocity: 0.5mL/min, absorbing wavelength: 214nm.
Structural identification result is as follows: 1h NMR (400MHz, CDCl 3) δ 8.65 (s, 1H), 8.23 (d, J=8.0Hz, 1H), 7.73 (d, J=1.2Hz, 1H), 7.62 (d, J=8.0Hz, 1H), 7.11 (d, J=8.0Hz, 2H), 7.05 (d, J=8.0Hz, 2H), 3.79-3.69 (m, 1H), 2.74-2.64 (m, 1H), 2.53-2.42 (m, 1H), 2.32 (s, 3H), 2.30-2.15 (m, 2H); 13c NMR (100MHz, CDCl 3) δ 161.1,136.7,136.3,136.09,136.07,133.4,130.6,129.6,129.5,128.4,125.2 (q, J c-F=279.0Hz), 117.1,116.0,71.0 (q, J c-F=28.0Hz), 30.8,29.9,21.0.
Embodiment 4, (R)-1,1,1-tri-fluoro-4-rubigan-2-butyraldehyde imines (see structural formula V-d)
(1) in reactor, add 2-chloro-4-cyano group benzylamine (399.9mg successively, 1.8mmol) and 4A molecular sieve (650mg), after vacuumizing logical nitrogen three times, add chloroform (4.5mL), acetic acid (108.1mg, 1.8mmol) stirs 20 minutes.Add 1,1, the fluoro-4-rubigan-2-butanone (354.9mg of 1-tri-, the oil bath return stirring of 80 DEG C is put into 1.5mmol), react and after 5 hours, reactor is taken out from oil bath, with being spin-dried for column chromatography (eluent is normal hexane: methylene dichloride=4/3) after diatomite filtration, in normal hexane, recrystallization obtains 427.6mg colorless solid trifluoromethyl ketoimine (shown in formula III-d), and yield is 74%.
Structural identification result is as follows: 1h NMR (400MHz, CDCl 3) δ 7.61 (s, IH), 7.52 (s, 2H), 7.20 (d, J=8.4Hz, 2H), 7.11 (d, J=8.4Hz2H), 4.39 (d, J=1.2Hz, 2H), 3.00-2.81 (m, 4H); 13cNMR (100MHz, CDCl 3) δ 160.8 (q, J c-F=3.3Hz), 141.5,137.7,133.5,133.0,132.4,130.7,129.8,129.6,129.2,120.0 (q, J c-F=278Hz), 117.7,112.5,51.8,31.6,29.8.
(2) in reactor, 1 is added successively, the fluoro-4-rubigan-2-butanone imines of 1,1-tri-(shown in formula III-d) (192.6mg, 0.5mmol), chiral base (shown in formula IV-a) (37.9mg, 0.05mmol) and 0.5mL benzene.Reactor is put into 50 DEG C of stirrings, by reaction solution column chromatography (eluent is normal hexane: ether=15/1) after 24 hours, obtain 191.2mg colourless liquid aldimine (shown in formula V-d), yield 99%.It is 93% that HPLC records enantiomeric excess numerical value.
HPLC condition: chirality AD-H post, moving phase: the volume ratio of normal hexane and Virahol is the mixed solvent of 95: 05, flow velocity: 0.5mL/min, absorbing wavelength: 214nm.
Structural identification result is as follows: 1h NMR (400MHz, CDCl 3) δ 8.65 (s, 1H), 8.21 (d, J=8.0Hz, 1H), 7.72 (d, J=1.2Hz, 1H), 7.61 (d, J=8.0Hz, 1H), 7.25 (d, J=8.0Hz, 2H), 7.08 (d, J=8.0Hz, 2H), 3.79-3.68 (m, 1H), 2.72-2.62 (m, 1H), 2.56-2.45 (m, 1H), 2.31-2.17 (m, 2H); 13c NMR (100MHz, CDCl 3) δ 161.3,138.5,136.24,136.18,133.5,132.4,130.6,129.9,129.7,129.0,125.1 (q, J c-F=279.0Hz), 117.1,116.2,71.1 (q, J c-F=28.0Hz), 30.8,29.9.
Embodiment 5, (R)-1,1,1-tri-fluoro-4-rubigan-2-butyraldehyde imines (see structural formula V-e)
(1) in reactor, add 2-chloro-4-cyano group benzylamine (399.9mg successively, 1.8mmol) and 4A molecular sieve (650mg), after vacuumizing logical nitrogen three times, add chloroform (4.5mL), acetic acid (108.1mg, 1.8mmol) stirs 20 minutes.Add 1,1, the fluoro-4-p-methoxyphenyl-2-butanone (348.3mg of 1-tri-, the oil bath return stirring of 80 DEG C is put into 1.5mmol), react and after 5 hours, reactor is taken out from oil bath, with being spin-dried for column chromatography (eluent is normal hexane: methylene dichloride=1/1) after diatomite filtration, in normal hexane, recrystallization obtains 422.3mg colorless solid trifluoromethyl ketoimine (shown in formula III-e), and yield is 74%.
Structural identification result is as follows: 1h NMR (400MHz, CDCl 3) δ 7.57 (s, 1H), 7.58-7.45 (m, 2H), 7.09 (d, J=8.4Hz, 2H), 6.77 (d, J=8.4Hz2H), 4.33 (s, 2H), 3.72 (s, 3H), 2.95-2.80 (m, 4H); 13c NMR (100MHz, CDCl 3) δ 161.1 (q, J c-F=3.2Hz), 158.6,141.8,133.5,132.2,131.2,130.6,129.6,129.4,120.0 (q, J c-F=278Hz), 117.6,114.4,112.1,55.2,51.6,31.4,30.2.
(2) in reactor, 1 is added successively, the fluoro-4-p-methoxyphenyl-2-butanone imines of 1,1-tri-(shown in formula III-e) (190.4mg, 0.5mmol), chiral base (shown in formula IV-a) (37.9mg, 0.05mmol) and 0.5mL benzene.Reactor is put into 20 DEG C of stirrings, by reaction solution column chromatography (eluent is sherwood oil: ether=12/1) after 72 hours, obtain 187.1mg colourless liquid aldimine (shown in formula V-e), yield 98%.It is 94% that HPLC records enantiomeric excess numerical value.
HPLC condition: chirality AD-H post, moving phase: the volume ratio of normal hexane and Virahol is the mixed solvent of 95: 05, flow velocity: 0.5mL/min, absorbing wavelength: 214nm.
Structural identification result is as follows: 1h NMR (400MHz, CDCl 3) δ 8.64 (s, 1H), 8.22 (d, J=8.4Hz, 1H), 7.72 (s, 1H), 7.60 (d, J=8.4Hz, 1H), 7.07 (d, J=8.4Hz, 2H), 6.83 (d, J=8.4Hz, 2H), 3.82-3.68 (m, 4H), 2.72-2.61 (m, 1H), 2.51-2.40 (m, 1H), 2.31-2.15 (m, 2H); 13c NMR (100MHZ, CDCl 3) δ 161.2,158.4,136.4,136.2,133.5,131.8,130.6,129.7,129.5,125.2 (q, J c-F=279.0Hz), 117.2,116.1,114.3,71.1 (q, J c-F=28.0Hz), 55.4,30.4,30.1.
Embodiment 6, (R)-1,1,1-tri-fluoro-4-(2-chloro-phenyl-)-2-butyraldehyde imines (see structural formula V-f)
(1) in reactor, add 2-chloro-4-cyano group benzylamine (499.8mg successively, 3mmol) with 4A molecular sieve (1.200g), after vacuumizing logical nitrogen three times, add chloroform (6mL), acetic acid (180.2mg, 3mmol) add 1, 1, the fluoro-4-of 1-tri-(2-chloro-phenyl-)-2-butanone (591.5mg, the oil bath return stirring of 80 DEG C is put into 2.5mmol), react and after 5 hours, reactor is taken out from oil bath, with being spin-dried for column chromatography (eluent is sherwood oil: methylene dichloride=5/4) after diatomite filtration, in normal hexane, recrystallization obtains 592.6mg colorless solid trifluoromethyl ketoimine (shown in formula III-f), yield is 61%.
Structural identification result is as follows: 1h NMR (400MHz, CDCl 3) δ 7.69-7.57 (m, 2H), 7.53 (d, J=1.2Hz1H), 7.40-7.30 (m, 1H), 7.24-7.12 (m, 3H), 4.52 (s, 2H), 3.12-3.02 (m, 2H), 2.95-2.84 (m, 2H); 13c NMR (100MHz, CDCl 3) δ 161.0 (q, J c-F=3.3Hz), 141.8,136.9,134.1,133.8,132.5,130.9,130.8,130.1,129.7,128.8,127.6,120.1 (q, J c-F=278Hz), 117.7,112.4,51.8,30.5,28.0.
(2) in reactor, 1 is added successively, 1, the fluoro-4-of 1-tri-(2-chloro-phenyl-)-2-butanone imines (shown in formula III-f) (214.8mg, 0.5mmol), chiral base (shown in formula IV-a) (37.9mg, 0.05mmol) and 0.5mL benzene.Reactor is put into 20 DEG C of stirrings, by reaction solution column chromatography (eluent is sherwood oil: ether=15/1) after 72 hours, obtain 210.3mg colourless liquid aldimine (shown in formula V-f), yield 98%.It is 94% that HPLC records enantiomeric excess numerical value.
HPLC condition: chirality OD-H post, moving phase: the volume ratio of normal hexane and Virahol is the mixed solvent of 95: 05, flow velocity: 0.5mL/min, absorbing wavelength: 214nm.
Structural identification result is as follows: 1h NMR (400MHz, CDCl 3) δ 8.74 (s, 1H), 8.22 (d, J=8.4Hz, 1H), 7.72 (d, J=1.2Hz, 1H), 7.61 (d, J=8.0Hz, 1H), 7.33 (d, J=7.6Hz1H), 7.22-7.12 (m, 3H), 3.85-3.75 (m, 1H), 2.80-2.66 (m, 2H), 2.37-2.16 (m, 2H); 13c NMR (100MHz, CDCl 3) δ 161.3,137.9,136.4,136.3,134.2,133.6,130.7,130.5,130.0,129.8,128.2,127.2,125.1 (q, J c-F=279.0Hz), 117.2,116.2,71.5, (q, J c-F=28.0Hz), 29.4,28.9.
Embodiment 7, (R)-1,1,1-tri-fluoro-5-methylthio group-2-enanthaldehyde imines (see structural formula V-h)
(1) in reactor, add 2-chloro-4-cyano group benzylamine (999.6mg successively, 6mmol) with 4A molecular sieve (1.920g), after vacuumizing logical nitrogen three times, add chloroform (11mL), acetic acid (540.4mg, 9mmol) add 1, 1, the fluoro-5-methylthio group-2-heptanone (744.8mg of 1-tri-, the oil bath return stirring of 80 DEG C is put into 4mmol), react and after 5 hours, reactor is taken out from oil bath, with being spin-dried for column chromatography (eluent is normal hexane: ether=7/1) after diatomite filtration, obtain 843.6mg white solid trifluoromethyl ketoimine (shown in formula III-h), yield is 63%.
Structural identification result is as follows: 1h NMR (400MHz, CDCl 3) δ 7.69 (d, J=8.0Hz, 1H), 7.65 (s, 1H), 7.56 (d, J=8.0Hz, 1H), 4.80 (s, 2H), 2.79-2.64 (m, 2H), 265-2.54 (m, 2H), 2.08 (s, 3H), 1.97-1.84 (m, 2H); 13c NMR (100MHz, CDCl 3) δ 162.0 (q, J c-F=3.3Hz), 141.7,133.8,132.6,132.5,130.8,129.9,119.9 (q, J c-F=278Hz), 117.5,112.5,51.8,33.9,26.8,24.9,15.4.
(2) in reactor, 1 is added successively, the fluoro-5-methylthio group-2-heptanone imines of 1,1-tri-(shown in formula III-h) (167.4mg, 0.5mmol), chiral base (shown in formula IV-a) (37.9mg, 0.05mmol) and 0.5mL benzene.Reactor is put into 35 DEG C of stirrings, by reaction solution column chromatography (eluent is sherwood oil: ether=15/1) after 72 hours, obtain 167.0mg weak yellow liquid aldimine (shown in formula formula V-h), yield 99%.It is 90% that HPLC records enantiomeric excess numerical value.
HPLC condition: chirality AS-H post, moving phase: the volume ratio of normal hexane and Virahol is the mixed solvent of 85: 15, flow velocity: 0.5mL/min, absorbing wavelength: 214nm.
Structural identification result is as follows: 1h NMR (400MHz, CDCl 3) δ 8.72 (s, 1H), 8.20 (d, J=8.4Hz, 1H), 7.71 (s, 1H), 7.60 (d, J=8.0Hz, 1H), 3.82-3.72 (m, 1H), 2.52 (t, J=7.2Hz, 2H), 2.11-1.92 (m, 5H), 1.65-1.47 (m, 2H); 13c NMR (100MHz, CDCl 3) δ 160.8,136.3,136.1,133.4,130.6,129.6,125.0 (q, J c-F=279.0Hz), 117.0,116.0,71.7 (q, J c-F=28.0Hz), 33.7,28.1,24.9,15.6.
The fluoro-2-propionic aldehyde imines (see structural formula V-i) of embodiment 8, (R)-3-cyclohexyl-1,1,1-tri-
(1) in reactor, add 2-chloro-4-cyano group benzylamine (999.6mg successively, 6mmol) with 4A molecular sieve (1.920g), after vacuumizing logical nitrogen three times, add chloroform (11mL), acetic acid (540.4mg, 9mmol) add 3-cyclohexyl-1, 1, the fluoro-2-acetone of 1-tri-(776.8mg, the oil bath return stirring of 80 DEG C is put into 4mmol), react and after 5 hours, reactor is taken out from oil bath, with being spin-dried for column chromatography (eluent is hexane: ether=15/1) after diatomite filtration, obtain 1.095g white solid trifluoromethyl ketoimine (shown in formula III-i), yield is 86%.
Structural identification result is as follows: 1h NMR (400MHz, CDCl 3) δ 7.72 (d, J=8.0Hz, 1H), 7.67 (s, 1H), 7.58 (d, J=8.0Hz, 1H), 4.76 (s, 2H, 2.45 (d, J=7.6Hz2H), 1.85-1.62 (m, 6H), 1.34-1.11 (m, 3H), 1.10-0.97 (m, 2H); 13c NMR (100MHz, CDCl 3) δ 162.3 (q, J c-F=3.2Hz), 142.0,133.7,132.5,130.8,129.9,119.8 (q, J c-F=278Hz), 117.6,112.4,52.2,36.2,35.8,33.6,26.2,26.0.
(2) in reactor, 3-cyclohexyl-1 is added successively, the fluoro-2-acetone imine of 1,1-tri-(shown in formula III-i) (171.4mg, 0.5mmol), chiral base (shown in formula IV-a) (37.9mg, 0.05mmol) and 0.5mL benzene.Reactor is put into 35 DEG C of stirrings, after 72 hours, reacting liquid temperature is increased to 50 DEG C and continues stirrings column chromatography (eluent is sherwood oil: ether=50/1) after 24 hours, obtain 164.3mg weak yellow liquid aldimine (shown in formula V-i), yield 96%.It is 94% that HPLC records enantiomeric excess numerical value.
HPLC condition: chirality AS-H post, moving phase: the volume ratio of normal hexane and Virahol is the mixed solvent of 95: 05, flow velocity: 0.5mL/min, absorbing wavelength: 214nm.
Structural identification result is as follows: 1h NMR (400MHz, CDCl 3) δ 8.70 (s, 1H), 8.20 (d, J=8.0Hz, 1H), 7.72 (s, 1H), 7.61 (d, J=8.0Hz, 1H), 3.94-3.83 (m, 1H), 1.88-1.60 (m, 7H), 1.24-1.10 (m, 4H), 1.08-0.96 (m, 1H), 0.96-0.84 (m, 1H); 13c NMR (100MHz, CDCl 3) δ 160.5,136.6,136.1,133.5,130.7,129.7,125.4 (q, J c-F=279.0Hz), 117.2,116.0,69.4 (q, J c-F=28.0Hz), 36.0,34.2,33.1,31.9,26.5,26.2,26.0.
Embodiment 9, (R)-1,1,1-trifluoro-5-in heptan alkynes-2-aldimine (see structural formula V-j)
(1) in reactor, add 2-chloro-4-cyano group benzylamine (999.6mg successively, 6mmol) with 4A molecular sieve (1.920g), after vacuumizing logical nitrogen three times, add chloroform (11mL), acetic acid (540.4mg, 9mmol) add 1, 1, 1-trifluoro-5-in heptan alkynes-2-ketone (656.5mg, the oil bath return stirring of 80 DEG C is put into 4mmol), react and after 5 hours, reactor is taken out from oil bath, with being spin-dried for column chromatography (eluent is sherwood oil: ether=15/1) after diatomite filtration, obtain 1.072g white solid trifluoromethyl ketoimine (shown in formula m-j), yield is 86%.
Structural identification result is as follows: 1h NMR (400MHZ, CDCl 3) δ 7.75 (d, J=18.0Hz, 1H), 7.71 (s, 1H), 759 (d..J=8.0Hz, 1H), 4.91 (s, 2H) 2.75 (t, J=11.2 Hz 2H), 2.58-2.46 (m, 2H), 1.70-1.58 (m, 3H); 13c NMR (100MHz, CDCl 3) δ 160.1 (q, J c-F=3.3Hz), 142.1,133.7,132.5,130.8,129.9,119.9 (q, J c-F=278Hz), 117.6,112.4,52.2,27.2,16.2,3.36.
(2) in reactor, 1 is added successively, 1,1-trifluoro-5-in heptan alkynes-2-ketoimine (shown in formula III-j) (156.0mg, 0.5mmol), chiral base (shown in formula IV-a) (37.9mg, 0.05mmol) and 0.5mL benzene.Reactor is put into 20 DEG C of stirrings, column chromatography (eluent is sherwood oil: ether=20/1) after 72 hours, obtain 148.3mg colourless liquid aldimine (shown in formula V-i), yield 95%.It is 90% that HPLC records enantiomeric excess numerical value.
HPLC condition: chirality AS-H post, moving phase: the volume ratio of normal hexane and Virahol is the mixed solvent of 95: 05, flow velocity: 0.5mL/min, absorbing wavelength: 214nm.
Structural identification result is as follows: 1h NMR (400MHz, CDCl 3) δ 8.81 (s, 1H), 8.20 (d, J=8.0Hz, 1H), 7.70 (d, J=1.2Hz, 1H), 7.59 (d, J=8.0Hz, 1H), 4.09-3.98 (m, 1H), 2.32-2.22 (m, 1H), 2.11-1.90 (m, 3H), 1.80-1.75 (m, 3H); 13c NMR (100MHz, CDCl 3) δ 161.5,136.5,136.3,133.5,130.6,129.7,125.3 (q, J c-F=279.0Hz), 117.1,116.1,78.1,76.3,70.2 (q, J c-F=28.0Hz), 27.5,14.7,3.5.
Embodiment 10, (R)-1,1,1-tri-fluoro-4-(2-bromophenyl) fourth-2-amine (see structural formula I-a)
(1) in reactor, add 2-chloro-4-cyano group benzylamine (624.8mg successively, 4mmol) with 4A molecular sieve (1.200g), after vacuumizing logical nitrogen three times, add chloroform (7mL), acetic acid (337.Smg, 5.6mmol) add 1,1, the fluoro-4-of 1-tri-(2-bromophenyl)-2-butanone (702.7mg, the oil bath return stirring of 80 DEG C is put into 2.5mmol), react and taken out from oil bath by reactor after 5 hours, obtain 1.051g white solid trifluoromethyl ketoimine (shown in formula III-g) by filtered through silica gel, yield is 97%.
Structural identification result is as follows: 1h NMR (400MHz, CDCl 3) δ 7.66-7.59 (m, 2H), 7.58-7.50 (m, 2H), 7.25-7.18 (m, 2H) 7.12-7.01 (m, 1H), 4.53 (s, 2H), 3.13-3.03 (m, 2H), 2.97-2.84 (m, 2H); 13c NMR (100MHz, CDCl 3) δ 160.9 (q, J c-F=3.3Hz), 141.8,138.6,133.7,133.4,132.4,130.9,130.8,129.7,129.0,124.4,120.1 (q, J c-F=278Hz), 117.7,112.4,51.9,32.9,28.1.
(2) in reactor, 1 is added successively, 1, the fluoro-4-of 1-tri-(2-bromophenyl)-2-butanone imines (shown in formula III-g) (214.8mg, 0.5mmol), chiral base (shown in formula IV-a) (37.9mg, 0.05mmol) and 0.5mL benzene.Reactor is put into 20 DEG C of stirrings, by reaction solution column chromatography (eluent is sherwood oil: ether=15/1) after 72 hours, obtain 210.3mg colourless liquid aldimine (shown in formula V-g), yield 98%.It is 94% that HPLC records enantiomeric excess numerical value.
HPLC condition: chirality OD-H post, moving phase: the volume ratio of normal hexane and Virahol is the mixed solvent of 95: 5, flow velocity: 0.5mL/min, absorbing wavelength: 214nm.
Structural identification result is as follows: 1h NMR (400MHz, CDCl 3) δ 8.75 (s, 1H), 8.23 (d, J=8.0Hz, 1H), 7.71 (d, J=1.2Hz, 1H), 7.60 (dd, J=8.0,0.8Hz, 1H), 7.51 (dd, J=8.0,1.2Hz, 1H), 7.27-7.17 (m, 2H), 7.10-7.03 (m, 1H), 3.88-3.77 (m, 1H), 2.80-2.67 (m, 2H), 2.36-2.16 (m, 2H); 13c NMR (100MHz, CDCl 3) δ 161.2,139.6,136.4,136.2,133.4,133.2,130.6,130.4,129.7,128.3,127.8,125.1 (q, J c-F=279.0Hz), 124.5,117.1,116.1,71.4 (q, J c-F=28.0Hz), 31.9,29.0.
(3) in reactor, aldimine (formula V-g) (1.05g is added successively, 4.9mmol), ether (12.5mL), ethylene glycol (25.0mL), 6N HCl (25ml)), in stirring at room temperature after 4 hours, by reaction solution with after ether (2*10mL) washing, after reaction solution use water (100mL) is diluted, after ether (4*30mL) washing, ether is used mutually 2N HCl (2*20mL) back extraction, after being merged by aqueous phase, use Na 2cO 3after adjust ph to 10, by aqueous phase with after methylene dichloride (5*40mL) extraction, merge organic phase, with being spin-dried for rear column chromatography (eluent is sherwood oil: ether=5/1) after dried over sodium sulfate, obtain 649.5mg colourless liquid (R)-4-(2-bromophenyl)-1,1,1-trifluoro fourth-2-amine (formula I-a), productive rate 92%.
Structural identification result is as follows: 1h NMR (400MHz, CDCl 3) δ 7.54 (d, J=7.6Hz, 1H), 7.27-7.21 (m, 2H), 7.11-7.04 (m, 1H), 3.20-3.01 (m, 2H), 2.88-2.78 (m, 1H), 2.11-2.00 (m, 1H), 1.72-1.61 (m, 1H), 1.39 (s, 2H); 13c NMR (100MHz, CDCl 3) δ 140.5,133.2,130.6,128.2,127.8,126.9 (q, J c-F=280.0Hz), 124.6,53.6 (q, J c-F=29.0Hz), 32.4,30.1.
Embodiment 11, (R)-2-trifluoromethyl tetrahydroquinoline (formula VI)
Add palladium (5.6mg in the reactor, 0.025mmol), BINAP (24.9mg, 0.04mmol), cesium carbonate (228.1mg, 0.7mmol), after vacuumizing logical nitrogen three times, by (R)-4-(2-bromophenyl)-1,1,1-trifluoro fourth-2-amine is dissolved in toluene (5mL), is added in described reactor, return stirring 4 hours.Column chromatography (eluent is sherwood oil: ether=20/1) will be spin-dried for after reaction solution diatomite filtration, obtain 92.1mg white solid (R)-2-trifluoromethyl tetrahydroquinoline, yield 91%.It is 94% that HPLC records enantiomeric excess numerical value.
HPLC condition: chirality OD-H post, moving phase: the volume ratio of normal hexane and Virahol is the mixed solvent of 95: 05, flow velocity: 0.5mL/min, absorbing wavelength: 209nm.
Structural identification result is as follows: 1h NMR (400MHz, CDCl 3) δ 7.07-6.97 (m, 2H), 6.74-6.68 (m, 1H), 6.59 (d, J=8.0Hz, 1H), 4.08 (br s, 1H), 3.92-3.81 (m, 1H), 2.82 (t, J=6.8Hz, 2H), 2.17-2.04 (m, 2H); 13c NMR (100MHz, CDCl 3) δ 142.2,129.2,127.4,126.0 (q, J c-F=279.0Hz), 120.9,118.6,114.8,53.0 (q, J c-F=30.0Hz), 24.5,21.0.
Experiment proves, the trifluoromethyl amine compound that the application protects has identical performance with existing trifluoromethyl amine compound.

Claims (8)

1. the preparation method of trifluoromethyl aldimine shown in formula V, comprises the steps:
(1) shown in 2-chloro-4-cyano group benzylamine and formula II, trifluorumethylketone carries out trifluoromethyl ketoimine shown in the formula that is obtained by reacting III under the catalysis of an acidic catalyst;
In formula II, formula III and formula V, R is selected from methyl, ethyl, n-propyl, normal-butyl, methylcyclohexyl, CH 3xCH 2cH 2cH 2, R 1cH=CHCH 2cH 2, R 1c ≡ CCH 2cH 2and ArCH 2cH 2in any one, wherein, X is selected from any one in Sauerstoffatom, sulphur atom and nitrogen-atoms, R 1be selected from any one in hydrogen atom, methyl, ethyl, phenyl and benzyl; Ar is selected from any one in thiophene, naphthyl and substituted-phenyl, and described substituted-phenyl is that ortho position, contraposition or a position are by the phenyl that in methyl, methoxyl group, nitro, cyano group, benzyloxy, fluorine atom, chlorine atom and bromine atoms, any one replaces;
(2) carry out turning aminating reaction under the catalysis of chiral base catalyzer that trifluoromethyl ketoimine shown in formula III derives at quinine shown in formula IV and obtain trifluoromethyl aldimine shown in formula V;
In formula IV, R 3be selected from any one in hydrogen atom, methyl, ethyl, n-propyl, allyl group, normal-butyl, benzoyl, ethanoyl and phenyl; R 4be selected from any one in ethyl and vinyl; Ar ' is phenyl or substituted-phenyl.
2. preparation method according to claim 1, is characterized in that: described in step (1), the solvent of reaction is any one in benzene,toluene,xylene, trimethylbenzene, bromobenzene, chloroform and acetonitrile; The temperature of described reaction is 50 ~ 130 DEG C, and the time is 3 ~ 24 hours.
3. preparation method according to claim 1 and 2, is characterized in that: in step (1), and 2-chloro-4-cyano group benzylamine is (1 ~ 3) with the molfraction ratio of trifluorumethylketone shown in formula II: 1.
4. preparation method according to claim 1, is characterized in that: in step (2), described in turn aminating reaction solvent be benzene,toluene,xylene, trimethylbenzene, bromobenzene, ethyl acetate, tetrahydrofuran (THF) or acetonitrile; The described temperature turning aminating reaction is 0 ~ 50 DEG C, and the time is 24 ~ 108h.
5. preparation method according to claim 1, is characterized in that: in step (2), and the chiral base catalyzer that quinine shown in formula IV derives is (1 ~ 3) with the molfraction ratio of trifluoromethyl ketoimine shown in formula III: 10.
6. the preparation method of trifluoromethyl amine shown in formula I, comprises the steps:
In formula I, R is selected from methyl, ethyl, n-propyl, normal-butyl, methylcyclohexyl, CH 3xCH 2cH 2cH 2, R 1cH=CHCH 2cH 2, R 1c ≡ CCH 2cH 2and ArCH 2cH 2in any one, wherein, X is selected from any one in Sauerstoffatom, sulphur atom and nitrogen-atoms, R 1be selected from any one in hydrogen atom, methyl, ethyl, phenyl and benzyl; Ar is selected from any one in thiophene, naphthyl and substituted-phenyl, and described substituted-phenyl is that ortho position, contraposition or a position are by the phenyl that in methyl, methoxyl group, nitro, cyano group, benzyloxy, fluorine atom, chlorine atom and bromine atoms, any one replaces;
Namely according to claim 1, trifluoromethyl aldimine shown in method preparation formula V, then obtain trifluoromethyl amine shown in formula I through hydrolysis reaction in acid condition by trifluoromethyl aldimine shown in described formula V.
7. preparation method according to claim 6, is characterized in that: the solvent of described hydrolysis reaction is tetrahydrofuran (THF), ether, toluene, methyl alcohol, ethanol or ethylene glycol;
Described hydrolysis reaction carries out under the condition of dilute hydrochloric acid, and the volumetric molar concentration of described dilute hydrochloric acid is 0.5 ~ 6.0 mol/L.
8. the preparation method according to claim 6 or 7, is characterized in that: the temperature of described hydrolysis reaction is 4 ~ 30 DEG C, and the time is 1 ~ 24 hour;
Described method also comprises and to extract described trifluoromethyl amine and the step of column chromatography for separation.
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