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

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 photoactive trifluoromethylamine compound and preparation method thereof

technical field

The invention relates to a photoactive trifluoromethylamine compound and a preparation method thereof.

Background technique

Due to the special physical properties of trifluoromethylamine compounds, photoactive trifluoromethylamine has important application value in the fields of medicine and agriculture. Many active pharmaceutical molecules are derived from photoactive trifluoromethylamine. Come. Trifluoromethylamine can be obtained by simple hydrolysis of trifluoromethylaldimine.

At present, the methods for preparing photoactive amines in organic synthesis mainly include the catalytic hydrogenation of trifluoromethylimine. .

Contents of the invention

The object of the present invention is to provide a kind of photoactive trifluoromethyl amine compound and preparation method thereof, the substrate range of this method is wide, reaction condition is mild, easy to operate, high yield, enantiomeric excess can be as high as 94 %, is a method with industrial production potential, and the trifluoromethylaldimine provided by the invention is an important organic synthesis intermediate.

The trifluoromethyl aldimine shown in the formula V provided by the present invention,

In formula V, R is selected from methyl, ethyl, n-propyl, n-butyl, methylcyclohexyl, CH ₃ XCH ₂ CH ₂ CH ₂ , R ₁ CH=CHCH ₂ CH ₂ , R ₁ C≡CCH ₂ Any one of CH ₂ and ArCH ₂ CH ₂ , wherein X is selected from any of oxygen atom, sulfur atom and nitrogen atom, and R ₁ is selected from any of hydrogen atom, methyl, ethyl, phenyl and benzyl One; Ar is selected from any one of thiophene, naphthyl and substituted phenyl, and the substituted phenyl is ortho, para or meta by methyl, methoxy, nitro, cyano, benzyloxy , a phenyl group substituted by any one of a fluorine atom, a chlorine atom and a bromine atom.

The preparation method of trifluoromethylaldimine shown in the formula V provided by the invention comprises the steps:

(1) 2-chloro-4-cyanobenzylamine and trifluoromethyl ketone shown in formula II react under the catalysis of acid catalyst to obtain trifluoromethyl ketimine shown in formula III;

In formula II and formula III, R is selected from methyl, ethyl, n-propyl, n-butyl, methylcyclohexyl, CH ₃ XCH ₂ CH ₂ CH ₂ , R ₁ CH=CHCH ₂ CH ₂ , R ₁ C Any one of three CCH ₂ CH ₂ and ArCH ₂ CH ₂ , wherein X is selected from any one of oxygen atom, sulfur atom and nitrogen atom, and R ₁ is selected from hydrogen atom, methyl, ethyl, phenyl and benzyl Ar is selected from any one of thiophene, naphthyl and substituted phenyl, and the substituted phenyl is ortho, para or meta by methyl, methoxy, nitro, cyano, A phenyl group substituted by any one of benzyloxy, fluorine atom, chlorine atom and bromine atom;

(2) trifluoromethyl ketimine shown in formula III carries out transamination reaction under the catalysis of chiral base catalyst derived from cinchona base shown in formula IV to obtain trifluoromethyl aldimine shown in formula V;

In formula IV, R ₃ is selected from any one of hydrogen atom, methyl, ethyl, n-propyl, allyl, n-butyl, benzoyl, acetyl and phenyl; R ₄ is selected from ethyl and Any of the vinyl groups; Ar' is phenyl or substituted phenyl.

In the above-mentioned preparation method, the solvent of the reaction described in step (1) is any one in benzene, toluene, dimethylbenzene, trimethylbenzene, bromobenzene chloroform and acetonitrile; The temperature of the described reaction is 50～130 ℃, specifically can 50°C, 80°C or 130°C, and the time is 3 to 24 hours, specifically 3 hours, 5 hours or 24 hours.

In the above-mentioned preparation method, in step (1), the mole fraction ratio of 2-chloro-4-cyanobenzylamine and trifluoromethyl ketone shown in formula II is (1～3): 1, specifically can be ( 1 to 1.6):1, 1.2:1, 1.5:1, 1.52:1 or 1.6:1.

In the above-mentioned preparation method, in step (2), the solvent of the transamination reaction is benzene, toluene, xylene, trimethylbenzene, bromobenzene, ethyl acetate, tetrahydrofuran or acetonitrile; the temperature of the transamination reaction 0-50°C, specifically 0°C, 20°C, 35°C or 50°C, and the time is 24-108 hours, specifically 24 hours, 72 hours or 108 hours.

In the above-mentioned preparation method, in step (2), the mole fraction ratio of the chiral base catalyst derived from cinchona base shown in formula IV and trifluoromethyl ketimine shown in formula III is (1～3): 10 , such as 1:10.

The trifluoromethylamine shown in the formula I provided by the present invention,

In formula I, R is selected from methyl, ethyl, n-propyl, n-butyl, methylcyclohexyl, CH ₃ XCH ₂ CH ₂ CH ₂ , R ₁ CH=CHCH ₂ CH ₂ , R ₁ C≡CCH ₂ Any one of CH ₂ and ArCH ₂ CH ₂ , wherein X is selected from any of oxygen atom, sulfur atom and nitrogen atom, and _R is selected from any of hydrogen atom, methyl, ethyl, phenyl and benzyl One; Ar is selected from any one of thiophene, naphthyl and substituted phenyl, and the substituted phenyl is ortho, para or meta by methyl, methoxy, nitro, cyano, benzyloxy A phenyl group substituted by any one of fluorine atom, chlorine atom and bromine atom;

The C atom marked with * in formula I is a chiral carbon.

The present invention also provides a preparation method of trifluoromethylamine shown in formula I, comprising the steps of:

The trifluoromethylaldimine shown in formula V is hydrolyzed under acidic conditions to obtain trifluoromethylamine shown in formula I.

In the above preparation method, the solvent for the hydrolysis reaction can be tetrahydrofuran, ether, toluene, methanol, ethanol or ethylene glycol;

The hydrolysis reaction is carried out under the condition of dilute hydrochloric acid, and the molar concentration of the dilute hydrochloric acid may be 0.5-6.0 mol/liter, such as 6.0 mol/liter.

In the above preparation method, the temperature of the hydrolysis reaction is 4-30°C, and the time is 1-24 hours, such as 4 hours at 20°C;

The method also includes the steps of extracting the trifluoromethylamine and separating by column chromatography, such as column chromatography using n-hexane and diethyl ether as eluents.

The preparation method provided by the present invention uses trifluoromethyl ketones of different structures as substrates, first synthesizes imines, uses chiral bases as catalysts, undergoes transamination, and then undergoes hydrolysis, resulting in high yield and high enantioselectivity A method for obtaining trifluoromethylamine, which has mild conditions, a wide range of substrates, high yield, and an enantiomeric excess of up to 94%, has great industrialization potential. The trifluoromethylimine compounds and trifluoromethylamine compounds provided by the present invention are important structural units of a class of important pharmaceutical intermediates, such as they can be prepared by mature organic synthesis reaction types such as coupling reactions 2 -trifluoromethyl tetrahydroquinoline compounds, so it has important application value in the synthesis of 2-trifluoromethyl tetrahydroquinoline compounds.

Detailed ways

The experimental methods used in the following examples are conventional methods unless otherwise specified.

The materials and reagents used in the following examples can be obtained from commercial sources unless otherwise specified.

The preparation method of the 2-chloro-4-cyanobenzylamine used in the following examples is as follows: a dry 1L three-necked flask is evacuated three times with nitrogen, and then adds 2-chloro-4-cyanotoluene (30g, 198mmol ), NBS (42.4g, 238mmol), AIBN (3.27g, 20mmol) carbon tetrachloride (700mL), at 90 ℃ of reflux stirring overnight, the reaction solution is cooled and then filtered and spin-dried after column chromatography (eluent is petroleum Ether/ethyl acetate=60/1-40/1), the obtained product was spin-dried to obtain 23.2g of 2-chloro-4-cyanobenzyl bromide, and 11.4g of raw materials were recovered, with a yield of 82%.

2-Chloro-4-cyanobenzyl bromide (10g, 43.4mmol) and HMTA (6.08g, 43.4mmol) were dissolved in 400mL ethanol, stirred at room temperature overnight, after the ethanol was poured out, ethanol (372mL) was added, concentrated hydrochloric acid (24.8mL) was refluxed and stirred for 2 hours, spin-dried the ethanol, added 100mL of water, washed with ethyl acetate (2*30mL), adjusted the pH of the aqueous phase to 10 with Na ₂ CO ₃ solid, and washed with chloroform (3*50mL) after extraction, drying and spin-drying followed by column chromatography (eluent is ethyl acetate/methanol/triethylamine=50/1/1), the resulting product was spin-dried to obtain 6.2g light yellow solid 2- Chloro-4-cyanobenzylamine, yield 85%.

The compound shown in the formula IV-a used in the following examples is prepared by the following method:

Quinine (10.18 g, 31.4 mmol) was dissolved in dry DMF (80 mL), and NaH (70% in oil) (3.23 g, 94.2 mmol) was added portionwise under nitrogen. After the reaction solution was stirred for one hour, dissolve the bromide shown in formula 4 in DMF (20mL), add it dropwise to the above solution, stir overnight at 40°C, add saturated saline and quench with ethyl acetate (3*200mL) After extraction, the organic phase was washed with brine, dried with MgSO ₄ and spin-dried.

NaH (70% dispersed in oil) (5.38 g, 157.0 mmol, washed with n-hexane) was dissolved in DMF (122 mL) as a suspension, and EtSH (19.82 g, 314 mmol) was added dropwise to the above suspension After the dropwise addition, after stirring for 20 minutes, dissolve the liquid obtained in the previous step in DMF (60mL), add dropwise to the above solution, stir overnight at 110 degrees, add 4N HCl, dilute with saline, and dilute with acetic acid After extraction with ethyl ester (3×200mL), the organic phase was adjusted to pH 10 with concentrated ammonia, washed with brine, dried over MgSO ₄ , spin-dried, and then column chromatographed to obtain the product shown in Formula 1.

The product represented by formula 1 (27.0 mmol) was dissolved in chloroform (200 mL), PhNTf ₂ (11.56 g, 32.5 mmol), Et ₃ N (6.28 g, 62.1 mmol) were added, and stirred overnight at room temperature. After washing with 2N HCl (2*40mL) and saturated aqueous sodium carbonate solution (2*40mL), MgSO ₄ was dried and then spin-dried to obtain the product shown in formula 2 by column chromatography.

The product shown in Formula 2 (21.48mmol), the amine shown in Formula 5 (25.77mmol), Pd(OAc) ₂ (0.241g, 1.07mmol), BINAP (1.070g, 1.72mmol) and Cs ₂ CO ₃ (9.798g , 30.07mmol) was added into the reactor, and after evacuating nitrogen for three times, toluene (210mL) was added, refluxed and stirred overnight. The reaction solution was filtered with diatomaceous earth and then spin-dried, and the compound represented by formula IV-a was obtained by column chromatography.

The reaction equation of the above process is:

The structure confirmation results of the compound represented by formula IV-a are as follows: ¹ H NMR (400MHz, CDCl ₃ ) δ8.69(d, J=4.8Hz, 1H), 8.14(s, 2H), 7.98(d, J=9.2 Hz, 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); ¹³ C NMR (100MHz, CDCl ₃ ) δ148.9, 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 21.7.

Embodiment 1, synthesis 1,1,1-trifluoro-2-heptanal imine (see structural formula V-a)

(1) Add 2-chloro-4-cyanobenzylamine (500mg, 3mmol) and 4A molecular sieves (1.2g) successively in the reactor, after evacuating nitrogen for three times, add chloroform (7.0mL), acetic acid (262mg, 4.4 mmol) was stirred for 20 minutes. After adding 1,1,1-trifluoro-2-heptanone (421mg, 2.5mmol), put it in an oil bath at 80°C and stir under reflux. After reacting for 5 hours, take the reactor out of the oil bath, and filter it with diatomaceous earth Spin-dry column chromatography (eluent: n-hexane: ether = 15/1) gave 692 mg of yellow solid trifluoromethyl ketimine (shown by formula III-a), with a yield of 85%.

The structure confirmation results are as follows: ¹ H NMR (400MHz, CDCl ₃ ) δ7.72(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); ¹³ C NMR (100MHz, CDCl ₃ ) δ163.0 (q, J _CF = 3.4 Hz), 141.9, 133.8, 132.6, 130.9, 130.0, 120.1 (q, J _CF = 272 Hz), 117.7, 112.6, 51.7, 32.0, 28.2, 25.7, 22.3, 13.7.

(2) Add 1,1,1-trifluoro-2-heptanone imine (shown in formula III-a) (158.1 mg, 0.5 mmol) and chiral base (shown in formula IV-a) to the reactor successively ) (37.9mg, 0.05mmol) and 0.5mL benzene. The reactor was stirred at 35° C., and after 72 hours, the reaction solution was subjected to column chromatography (eluent was n-hexane: ether=20/1) to obtain 150.2 mg of a colorless liquid aldimine (shown in formula V-a) , yield 95%. The enantiomeric excess value by HPLC was 93%.

HPLC conditions: chiral AS-H column, mobile phase: mixed solvent with a volume ratio of n-hexane and isopropanol of 95:5, flow rate: 0.5 mL/min, absorption wavelength: 214 nm.

The structure confirmation results are as follows: ¹ H NMR (400MHz, CDCl ₃ ) δ8.70(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); ¹³ C NMR (100MHz, CDCl ₃ ) δ160.4, 136.5, 136.1, 133.4, 130.6, 129.7, 125.3 (q, J _CF =279.0Hz), 117.1, 116.0, 72.1 (q, J _CF =28.0Hz), 31.3, 28.8, 25.0, 22.5, 14.0.

Embodiment 2, synthesis 1,1,1-trifluoro-5-methoxy-2-heptanal imine (formula V-b)

(1) Add 2-chloro-4-cyanobenzylamine (625mg, 3.8mmol) and 4A molecular sieves (1.2g) successively in the reactor, after evacuating nitrogen for three times, add chloroform (7.0mL), acetic acid (338mg , 5.6mmol) was stirred for 20 minutes. After adding 1,1,1-trifluoro-5-methoxy-2-heptanone (425mg, 2.5mmol), put it into an oil bath at 50°C and stir under reflux. After 24 hours of reaction, the reactor was taken out from the oil bath. After filtering through silica gel and spin-drying, 701 mg of light yellow solid trifluoromethyl ketimine (shown by formula III-b) was obtained, with a yield of 88%.

The structure confirmation results are as follows: ¹ H NMR (400MHZ, CDCl ₃ ) δ7.71(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); ¹³ C NMR (100MHz, CDCl ₃ ) δ 162.3 (q, J _CF = 3.2 Hz), 142.0, 133.8, 132.4, 130.8, 129.8, 119.9 (q, J _CF = 278 Hz), 117.6, 112.4, 71.1, 58.7, 51.7, 26.1, 24.8.

(2) 1,1,1-trifluoro-5-methoxy-2-heptanone imine (shown in formula III-b) (159.4 mg, 0.5 mmol) (159.4 mg, 0.5 mmol) and chiral base ( Formula IV-a) (37.9mg, 0.05mmol) and 0.5mL benzene. The reactor was stirred at 0°C, and after 108 hours, the reaction solution was subjected to column chromatography (eluent was n-hexane: ether=8/1) to obtain 147.6 mg of a colorless liquid aldimine (shown in formula V-b) , yield 93%. The enantiomeric excess value by HPLC was 86%.

HPLC conditions: chiral AS-H column, mobile phase: mixed solvent with a volume ratio of n-hexane and isopropanol of 95:5, flow rate: 0.5 mL/min, absorption wavelength: 214 nm.

The structure confirmation results are as follows: ¹ H NMR (400MHz, CDCl ₃ ) δ8.73(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 ); ¹³ C NMR (100MHz, CDCl ₃ ) δ 160.9, 136.5, 136.2, 133.5, 130.6, 129.7, 125.2 (q, J _CF = 279.0 Hz), 117.2, 116.1, 72.20, 71.9 (q, J _CF = 28.0 Hz), 58.8, 26.2, 25.6.

Example 3, (R)-1,1,1-trifluoro-4-p-tolyl-2-butanaldimine (see structural formula V-c)

(1) Add 2-chloro-4-cyanobenzylamine (399.9mg, 1.8mmol) and 4A molecular sieves (650mg) successively in the reactor, after vacuumizing nitrogen for three times, add chloroform (4.5mL), acetic acid (108.1 mg, 1.8 mmol) was stirred for 20 minutes. Add 1,1,1-trifluoro-4-p-tolyl-2-butanone (324.3mg, 1.5mmol) and put it in an oil bath at 130°C for reflux and stirring. After reacting for 3 hours, take the reactor out of the oil bath , spin-dry column chromatography (eluent is n-hexane: dichloromethane=4/3) after filtering with celite, and recrystallize in n-hexane to obtain 427.0mg colorless solid trifluoromethyl ketimine (Shown by formula III-c), the yield is 78%.

The structure confirmation results are as follows: ¹ H NMR (400MHz, CDCl ₃ ) δ7.60(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); ¹³ C NMR (100 MHz, CDCl ₃ ) δ161.2 (q, J _CF =3.2 Hz), 141.9, 136.6, 136.2, 133.6, 132.3, 130.7, 129.7, 128.44, 128.36, 120.0 (q, J _CF =278 Hz), 117.6, 112.2, 51.7, 31.9, 30.2, 21.1.

(2) Add 1,1,1-trifluoro-4-p-tolyl-2-butanoneimine (shown in formula III-c) (182.4mg, 0.5mmol) successively in the reactor, chiral base ( Formula IV-a) (37.9mg, 0.05mmol) and 0.5mL benzene. The reactor was stirred at 20°C, and after 72 hours, the reaction solution was subjected to column chromatography (eluent: petroleum ether: ether=15/1) to obtain 180.6 mg of a colorless liquid aldimine (shown in formula V-c), Yield 99%. The enantiomeric excess value by HPLC was 94%.

HPLC conditions: chiral AD-H column, mobile phase: mixed solvent with a volume ratio of n-hexane and isopropanol of 95:5, flow rate: 0.5 mL/min, absorption wavelength: 214 nm.

The structure confirmation results are as follows: ¹ H NMR (400MHz, CDCl ₃ ) δ8.65(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); ¹³ C NMR (100MHz, CDCl ₃ ) δ161.1, 136.7, 136.3, 136.09, 136.07, 133.4, 130.6 , 129.6, 129.5, 128.4, 125.2 (q, J _CF =279.0 Hz), 117.1, 116.0, 71.0 (q, J _CF =28.0 Hz), 30.8, 29.9, 21.0.

Example 4, (R)-1,1,1-trifluoro-4-p-chlorophenyl-2-butanaldimine (see structural formula V-d)

(1) Add 2-chloro-4-cyanobenzylamine (399.9mg, 1.8mmol) and 4A molecular sieves (650mg) successively in the reactor, after vacuumizing nitrogen for three times, add chloroform (4.5mL), acetic acid (108.1 mg, 1.8 mmol) was stirred for 20 minutes. After adding 1,1,1-trifluoro-4-p-chlorophenyl-2-butanone (354.9mg, 1.5mmol), put it in an oil bath at 80°C and stir under reflux. After reacting for 5 hours, remove the reactor from the oil bath Take out, spin dry column chromatography (eluent is n-hexane: dichloromethane=4/3) after filtering with diatomaceous earth, recrystallize in n-hexane to obtain 427.6mg colorless solid trifluoromethyl ketone Amine (shown by formula III-d), the yield is 74%.

The structure confirmation results are as follows: ¹ H NMR (400MHz, CDCl ₃ ) δ7.61(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); ¹³ CNMR (100MHz, CDCl ₃ ) δ160.8 (q, J _CF = 3.3Hz), 141.5, 137.7, 133.5, 133.0, 132.4, 130.7, 129.8, 129.6, 129.2, 120.0 (q, J _CF =278 Hz), 117.7, 112.5, 51.8, 31.6, 29.8.

(2) Add 1,1,1-trifluoro-4-p-chlorophenyl-2-butanone imine (shown in formula III-d) (192.6 mg, 0.5 mmol) successively to the reactor, chiral base (Formula IV-a) (37.9mg, 0.05mmol) and 0.5mL benzene. The reactor was stirred at 50° C., and after 24 hours, the reaction solution was subjected to column chromatography (eluent: n-hexane: ether=15/1) to obtain 191.2 mg of a colorless liquid aldimine (shown in formula V-d) , yield 99%. The enantiomeric excess value by HPLC was 93%.

HPLC conditions: chiral AD-H column, mobile phase: mixed solvent with a volume ratio of n-hexane and isopropanol of 95:05, flow rate: 0.5 mL/min, absorption wavelength: 214 nm.

The structure confirmation results are as follows: ¹ H NMR (400MHz, CDCl ₃ ) δ8.65(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); ¹³ C NMR (100MHz, CDCl ₃ ) δ161.3, 138.5, 136.24, 136.18, 133.5, 132.4, 130.6, 129.9, 129.7, 129.0, 125.1 (q, J _CF =279.0 Hz), 117.1, 116.2, 71.1 (q, J _CF =28.0 Hz), 30.8, 29.9.

Example 5, (R)-1,1,1-trifluoro-4-p-chlorophenyl-2-butanaldimine (see structural formula V-e)

(1) Add 2-chloro-4-cyanobenzylamine (399.9mg, 1.8mmol) and 4A molecular sieves (650mg) successively in the reactor, after vacuumizing nitrogen for three times, add chloroform (4.5mL), acetic acid (108.1 mg, 1.8 mmol) was stirred for 20 minutes. After adding 1,1,1-trifluoro-4-p-methoxyphenyl-2-butanone (348.3mg, 1.5mmol), put it in an oil bath at 80°C for reflux and stir, and after 5 hours of reaction, remove the reactor from Take it out from the oil bath, filter it with diatomaceous earth and spin dry column chromatography (eluent is n-hexane: dichloromethane = 1/1), recrystallize in n-hexane to obtain 422.3mg colorless solid trifluoromethyl The yield of ketimine (shown by formula III-e) is 74%.

The structure confirmation results are as follows: ¹ H NMR (400MHz, CDCl ₃ ) δ7.57(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); ¹³ C NMR (100MHz, CDCl ₃ ) δ161.1(q, J _CF =3.2Hz), 158.6 , 141.8, 133.5, 132.2, 131.2, 130.6, 129.6, 129.4, 120.0 (q, J _CF =278 Hz), 117.6, 114.4, 112.1, 55.2, 51.6, 31.4, 30.2.

(2) Add 1,1,1-trifluoro-4-p-methoxyphenyl-2-butanone imine (shown in formula III-e) (190.4 mg, 0.5 mmol) successively to the reactor, and Alkali (represented by formula IV-a) (37.9mg, 0.05mmol) and 0.5mL benzene. The reactor was stirred at 20°C, and after 72 hours, the reaction solution was subjected to column chromatography (eluent: petroleum ether: ether=12/1) to obtain 187.1 mg of a colorless liquid aldimine (shown in formula V-e), Yield 98%. The enantiomeric excess value by HPLC was 94%.

HPLC conditions: chiral AD-H column, mobile phase: mixed solvent with a volume ratio of n-hexane and isopropanol of 95:05, flow rate: 0.5 mL/min, absorption wavelength: 214 nm.

The structure confirmation results are as follows: ¹ H NMR (400MHz, CDCl ₃ ) δ8.64(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); ¹³ C NMR (100MHZ, CDCl ₃ ) δ161.2, 158.4, 136.4, 136.2, 133.5, 131.8, 130.6, 129.7, 129.5, 125.2 (q, J _CF = 279.0 Hz), 117.2, 116.1, 114.3, 71.1 (q, J _CF =28.0 Hz), 55.4, 30.4, 30.1.

Example 6, (R)-1,1,1-trifluoro-4-(2-chlorophenyl)-2-butanaldimine (see structural formula V-f)

(1) Add 2-chloro-4-cyanobenzylamine (499.8mg, 3mmol) and 4A molecular sieves (1.200g) to the reactor successively, after vacuuming nitrogen for three times, add chloroform (6mL), acetic acid (180.2mg , 3mmol) after adding 1,1,1-trifluoro-4-(2-chlorophenyl)-2-butanone (591.5mg, 2.5mmol), put it in an oil bath at 80°C under reflux and stir, and react for 5 hours The reactor was taken out from the oil bath, filtered through diatomaceous earth and then spin-dried for column chromatography (eluent: petroleum ether: dichloromethane=5/4), and recrystallized in n-hexane to obtain 592.6 mg of a colorless solid three Fluoromethyl ketimine (shown by formula III-f), the yield is 61%.

The structure confirmation results are as follows: ¹ H NMR (400MHz, CDCl ₃ ) δ7.69-7.57 (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); ¹³ C NMR (100MHz, CDCl ₃ ) δ161.0(q, J _CF =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 _CF = 278Hz), 117.7, 112.4, 51.8, 30.5, 28.0.

(2) Add 1,1,1-trifluoro-4-(2-chlorophenyl)-2-butanoneimine (shown in formula III-f) (214.8 mg, 0.5 mmol) sequentially into the reactor, Chiral base (formula IV-a) (37.9mg, 0.05mmol) and 0.5mL benzene. The reactor was stirred at 20°C, and after 72 hours, the reaction solution was subjected to column chromatography (eluent: petroleum ether: ether=15/1) to obtain 210.3 mg of a colorless liquid aldimine (shown in formula V-f), Yield 98%. The enantiomeric excess value by HPLC was 94%.

HPLC conditions: chiral OD-H column, mobile phase: mixed solvent with a volume ratio of n-hexane and isopropanol of 95:05, flow rate: 0.5 mL/min, absorption wavelength: 214 nm.

The structure confirmation results are as follows: ¹ H NMR (400MHz, CDCl ₃ ) δ8.74(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); ¹³ C NMR (100MHz, CDCl ₃ ) δ161.3, 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 _CF = 279.0Hz) , 117.2, 116.2, 71.5, (q, J _CF =28.0 Hz), 29.4, 28.9.

Example 7, (R)-1,1,1-trifluoro-5-methylthio-2-heptanal imine (see structural formula V-h)

(1) Add 2-chloro-4-cyanobenzylamine (999.6mg, 6mmol) and 4A molecular sieves (1.920g) to the reactor successively, after vacuuming nitrogen for three times, add chloroform (11mL), acetic acid (540.4mg , 9mmol) after adding 1,1,1-trifluoro-5-methylthio-2-heptanone (744.8mg, 4mmol), put it into an oil bath at 80°C and stir under reflux, and after 5 hours of reaction, the reactor was removed from the oil The bath was taken out, filtered with diatomaceous earth and then spin-dry column chromatography (eluent is n-hexane: ether=7/1), to obtain 843.6 mg of white solid trifluoromethyl ketimine (shown in formula III-h) , the yield was 63%.

The structure confirmation results are as follows: ¹ H NMR (400MHz, CDCl ₃ ) δ7.69(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); ¹³ C NMR (100MHz, CDCl ₃ ) δ162.0 (q, J _CF = 3.3 Hz), 141.7, 133.8, 132.6, 132.5, 130.8, 129.9, 119.9 (q, J _CF = 278 Hz), 117.5, 112.5, 51.8, 33.9, 26.8, 24.9, 15.4.

(2) 1,1,1-trifluoro-5-methylthio-2-heptanone imine (shown in formula III-h) (167.4mg, 0.5mmol) (167.4mg, 0.5mmol) and chiral base ( Formula IV-a) (37.9mg, 0.05mmol) and 0.5mL benzene. The reactor was stirred at 35°C, and after 72 hours, the reaction solution was subjected to column chromatography (eluent: petroleum ether: ether = 15/1) to obtain 167.0 mg of light yellow liquid aldimine (shown in formula V-h) , yield 99%. The enantiomeric excess value by HPLC was 90%.

HPLC conditions: chiral AS-H column, mobile phase: mixed solvent with a volume ratio of n-hexane and isopropanol of 85:15, flow rate: 0.5 mL/min, absorption wavelength: 214 nm.

The structure confirmation results are as follows: ¹ H NMR (400MHz, CDCl ₃ ) δ8.72(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); ¹³ C NMR (100MHz, CDCl ₃ ) δ 160.8, 136.3, 136.1, 133.4, 130.6, 129.6, 125.0 (q, J _CF = 279.0 Hz), 117.0, 116.0, 71.7 (q, J _CF = 28.0 Hz), 33.7, 28.1, 24.9, 15.6.

Example 8, (R)-3-cyclohexyl-1,1,1-trifluoro-2-propionaldimine (see structural formula V-i)

(1) Add 2-chloro-4-cyanobenzylamine (999.6mg, 6mmol) and 4A molecular sieves (1.920g) to the reactor successively, after vacuuming nitrogen for three times, add chloroform (11mL), acetic acid (540.4mg , 9mmol) after adding 3-cyclohexyl-1,1,1-trifluoro-2-propanone (776.8mg, 4mmol), put it into an oil bath at 80°C for reflux and stir, and after 5 hours of reaction, remove the reactor from the oil bath Take out, spin dry column chromatography (eluent is normal ethane: ethyl ether=15/1) after filtering with diatomaceous earth, obtain 1.095g white solid trifluoromethyl ketimine (shown in formula III-i), The yield was 86%.

The structure confirmation results are as follows: ¹ H NMR (400MHz, CDCl ₃ ) δ7.72(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); ¹³ C NMR (100MHz, CDCl ₃ ) δ162 .3 (q, J _CF = 3.2 Hz), 142.0, 133.7, 132.5, 130.8, 129.9, 119.8 (q, J _CF = 278 Hz), 117.6, 112.4, 52.2, 36.2, 35.8, 33.6, 26.2, 26.0.

(2) Add 3-cyclohexyl-1,1,1-trifluoro-2-acetonimine (shown in formula III-i) (171.4 mg, 0.5 mmol) successively to the reactor, chiral base (formula IV-a) (37.9mg, 0.05mmol) and 0.5mL benzene. The reactor was stirred at 35°C, and after 72 hours, the temperature of the reaction solution was raised to 50°C and continued to stir for 24 hours, followed by column chromatography (eluent: petroleum ether: ether=50/1), and 164.3 mg of light yellow was obtained. Liquid aldimine (shown by formula V-i), the yield is 96%. The enantiomeric excess value by HPLC was 94%.

HPLC conditions: chiral AS-H column, mobile phase: mixed solvent with a volume ratio of n-hexane and isopropanol of 95:05, flow rate: 0.5 mL/min, absorption wavelength: 214 nm.

The structure confirmation results are as follows: ¹ H NMR (400MHz, CDCl ₃ ) δ8.70(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); ¹³ C NMR (100MHz, CDCl ₃ ) δ 160.5, 136.6, 136.1, 133.5, 130.7, 129.7, 125.4 (q, J _CF = 279.0 Hz), 117.2, 116.0, 69.4 (q, J _CF = 28.0 Hz), 36.0, 34.2, 33.1, 31.9, 26.5, 26.2, 26.0.

Example 9, (R)-1,1,1-trifluorohept-5-yne-2-aldimine (see structural formula V-j)

(1) Add 2-chloro-4-cyanobenzylamine (999.6mg, 6mmol) and 4A molecular sieves (1.920g) to the reactor successively, after vacuuming nitrogen for three times, add chloroform (11mL), acetic acid (540.4mg , 9mmol) after adding 1,1,1-trifluorohept-5-yn-2-one (656.5mg, 4mmol), put it into an oil bath at 80°C for reflux and stir, and take the reactor out from the oil bath after reacting for 5 hours , spin dry column chromatography (eluent is sherwood oil: ether=15/1) after filtering with diatomaceous earth, obtain 1.072g white solid trifluoromethyl ketimine (shown in formula m-j), yield is 86 %.

The structure confirmation results are as follows: ¹ H NMR (400MHZ, CDCl ₃ ) δ7.75(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); ¹³ C NMR (100MHz, CDCl ₃ ) δ160.1 (q, J _CF = 3.3 Hz), 142.1, 133.7, 132.5, 130.8, 129.9, 119.9 (q, J _CF = 278 Hz), 117.6, 112.4, 52.2, 27.2, 16.2, 3.36.

(2) Add 1,1,1-trifluorohept-5-yne-2-ketimine (shown in formula III-j) (156.0 mg, 0.5 mmol) and chiral base (formula IV -a) (37.9mg, 0.05mmol) and 0.5mL benzene. The reactor was stirred at 20° C., and after 72 hours, column chromatography (eluent was petroleum ether: ether=20/1) obtained 148.3 mg of colorless liquid aldimine (shown in formula V-i), yield 95 %. The enantiomeric excess value by HPLC was 90%.

HPLC conditions: chiral AS-H column, mobile phase: mixed solvent with a volume ratio of n-hexane and isopropanol of 95:05, flow rate: 0.5 mL/min, absorption wavelength: 214 nm.

The structure confirmation results are as follows: ¹ H NMR (400MHz, CDCl ₃ ) δ8.81(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); ¹³ C NMR (100MHz , CDCl ₃ ) δ161.5, 136.5, 136.3, 133.5, 130.6, 129.7, 125.3 (q, J _CF =279.0Hz), 117.1, 116.1, 78.1, 76.3, 70.2 (q, J _CF =28.0Hz), 27.5, 14.7, 3.5.

Example 10, (R)-1,1,1-trifluoro-4-(2-bromophenyl)butan-2-amine (see structural formula I-a)

(1) Add 2-chloro-4-cyanobenzylamine (624.8mg, 4mmol) and 4A molecular sieves (1.200g) successively in the reactor, after vacuumizing nitrogen for three times, add chloroform (7mL), acetic acid (337. Smg, 5.6mmol) was added with 1,1,1-trifluoro-4-(2-bromophenyl)-2-butanone (702.7mg, 2.5mmol) and then placed in an oil bath at 80°C under reflux and stirring, reaction 5 After one hour, the reactor was taken out from the oil bath and filtered through silica gel to obtain 1.051 g of white solid trifluoromethyl ketimine (shown by formula III-g), with a yield of 97%.

The structure confirmation results are as follows: ¹ H NMR (400MHz, CDCl ₃ ) δ7.66-7.59 (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); ¹³ C NMR (100MHz, CDCl ₃ ) δ160.9(q, J _CF =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 _CF = 278 Hz), 117.7, 112.4, 51.9, 32.9, 28.1.

(2) Add 1,1,1-trifluoro-4-(2-bromophenyl)-2-butanoneimine (shown in formula III-g) (214.8 mg, 0.5 mmol) sequentially into the reactor, Chiral base (formula IV-a) (37.9mg, 0.05mmol) and 0.5mL benzene. The reactor was stirred at 20°C, and after 72 hours, the reaction solution was subjected to column chromatography (eluent: petroleum ether: ether=15/1) to obtain 210.3 mg of a colorless liquid aldimine (shown in formula V-g), Yield 98%. The enantiomeric excess value by HPLC was 94%.

HPLC conditions: chiral OD-H column, mobile phase: mixed solvent with a volume ratio of n-hexane and isopropanol of 95:5, flow rate: 0.5 mL/min, absorption wavelength: 214 nm.

The structure confirmation results are as follows: ¹ H NMR (400MHz, CDCl ₃ ) δ8.75(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); ¹³ C NMR (100MHz, CDCl ₃ ) δ161.2, 139.6, 136.4, 136.2, 133.4, 133.2, 130.6, 130.4, 129.7, 128.3 , 127.8, 125.1 (q, J _CF = 279.0 Hz), 124.5, 117.1, 116.1, 71.4 (q, J _CF = 28.0 Hz), 31.9, 29.0.

(3) Add aldimine (formula Vg) (1.05g, 4.9mmol), diethyl ether (12.5mL), ethylene glycol (25.0mL), 6N HCl (25ml)) successively in the reactor, stir at room temperature for 4 hours After that, the reaction solution was washed with ether (2*10mL), diluted with water (100mL), washed with ether (4*30mL), and the ether phase was back-extracted with 2N HCl (2*20mL). After the aqueous phases were combined, the pH value was adjusted to 10 with Na ₂ CO ₃ , the aqueous phase was extracted with dichloromethane (5*40mL), the organic phases were combined, dried with sodium sulfate, spin-dried, and then column chromatography (elution The agent is petroleum ether: ether=5/1), obtains 649.5mg colorless liquid (R)-4-(2-bromophenyl)-1,1,1-trifluorobutan-2-amine (formula Ia), Yield 92%.

The structure confirmation results are as follows: ¹ H NMR (400MHz, CDCl ₃ ) δ7.54 (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); ¹³ C NMR (100MHz, CDCl ₃ ) δ140. 5, 133.2, 130.6, 128.2, 127.8, 126.9 (q, J _CF =280.0 Hz), 124.6, 53.6 (q, J _CF =29.0 Hz), 32.4, 30.1.

Embodiment 11, (R)-2-trifluoromethyltetrahydroquinoline (formula VI)

Palladium acetate (5.6mg, 0.025mmol), BINAP (24.9mg, 0.04mmol), cesium carbonate (228.1mg, 0.7mmol) were added in the reactor, and after three times of vacuumizing nitrogen, the (R)-4-(2 -Bromophenyl)-1,1,1-trifluorobutan-2-amine was dissolved in toluene (5 mL), added to the reactor, and stirred at reflux for 4 hours. The reaction solution was filtered with diatomaceous earth and then spin-dry column chromatography (eluent: petroleum ether: diethyl ether = 20/1) to obtain 92.1 mg of white solid (R)-2-trifluoromethyltetrahydroquinoline. The rate is 91%. The enantiomeric excess value by HPLC was 94%.

HPLC conditions: chiral OD-H column, mobile phase: mixed solvent with a volume ratio of n-hexane and isopropanol of 95:05, flow rate: 0.5 mL/min, absorption wavelength: 209 nm.

The structure confirmation results are as follows: ¹ H NMR (400MHz, CDCl ₃ ) δ7.07-6.97 (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); ¹³ C NMR (100MHz, CDCl ₃ ) δ142.2, 129.2, 127.4 , 126.0 (q, J _CF =279.0 Hz), 120.9, 118.6, 114.8, 53.0 (q, J _CF =30.0 Hz), 24.5, 21.0.

Experiments have proved that the trifluoromethylamine compound protected by this application has the same performance as the existing trifluoromethylamine compound.

Claims (8)

1. the preparation method of trifluoromethyl aldimine shown in formula V comprises the steps: (1) 2-chloro-4-cyanobenzylamine and trifluoromethyl ketone shown in formula II react under the catalysis of acid catalyst to obtain trifluoromethyl ketimine shown in formula III; In formula II, formula III and formula V, R is selected from methyl, ethyl, n-propyl, n-butyl, methylcyclohexyl, CH ₃ XCH ₂ CH ₂ CH ₂ , R ₁ CH=CHCH ₂ CH ₂ , Any of R ₁ C≡CCH ₂ CH ₂ and ArCH ₂ CH ₂ , wherein X is selected from any of oxygen atom, sulfur atom and nitrogen atom, and R ₁ is selected from hydrogen atom, methyl, ethyl, benzene Any one of base and benzyl; Ar is selected from any one of thiophene, naphthyl and substituted phenyl, and the substituted phenyl is ortho, para or meta by methyl, methoxy, nitro, A phenyl group substituted by any one of cyano, benzyloxy, fluorine atom, chlorine atom and bromine atom; (2) trifluoromethyl ketimine shown in formula III carries out a transamination reaction under the catalysis of a chiral base catalyst derived from cinchona base shown in formula IV to obtain trifluoromethyl aldimine shown in formula V; In formula IV, R ₃ is selected from any one of hydrogen atom, methyl, ethyl, n-propyl, allyl, n-butyl, benzoyl, acetyl and phenyl; R ₄ is selected from ethyl and Any of the vinyl groups; Ar' is phenyl or substituted phenyl. 2. preparation method according to claim 1, is characterized in that: the solvent of reaction described in step (1) is any in benzene, toluene, dimethylbenzene, mesitylene, bromobenzene, chloroform and acetonitrile; The temperature of reaction is 50～130 ℃, and the time is 3～24 hours. 3. according to the described preparation method of claim 1 or 2, it is characterized in that: in step (1), the mol fraction ratio of 2-chloro-4-cyanobenzylamine and trifluoromethyl ketone shown in formula II is (1~3): 1. 4. preparation method according to claim 1 is characterized in that: in step (2), the solvent of described transamination reaction is benzene, toluene, xylene, trimethylbenzene, bromobenzene, ethyl acetate, tetrahydrofuran or Acetonitrile; the temperature of the transamination reaction is 0-50° C., and the time is 24-108 h. 5. preparation method according to claim 1 is characterized in that: in step (2), the molar part of the chiral base catalyst derived from cinchona base shown in formula IV and trifluoromethyl ketimine shown in formula III The number ratio is (1~3):10. 6. the preparation method of trifluoromethylamine shown in formula I, comprises the steps: In formula I, R is selected from methyl, ethyl, n-propyl, n-butyl, methylcyclohexyl, CH ₃ XCH ₂ CH ₂ CH ₂ , R ₁ CH=CHCH ₂ CH ₂ , R ₁ C≡CCH ₂ Any one of CH ₂ and ArCH ₂ CH ₂ , wherein X is selected from any of oxygen atom, sulfur atom and nitrogen atom, and _R is selected from any of hydrogen atom, methyl, ethyl, phenyl and benzyl One; Ar is selected from any one of thiophene, naphthyl and substituted phenyl, and the substituted phenyl is ortho, para or meta by methyl, methoxy, nitro, cyano, benzyloxy A phenyl group substituted by any one of fluorine atom, chlorine atom and bromine atom; According to the method described in claim 1, trifluoromethylaldimine shown in formula V is prepared, and then trifluoromethylaldimine shown in formula V is hydrolyzed under acidic conditions to obtain trifluoromethylaldimine shown in formula I. Methylamine. 7. The preparation method according to claim 6, characterized in that: the solvent of the hydrolysis reaction is THF, ether, toluene, methyl alcohol, ethanol or ethylene glycol; The hydrolysis reaction is carried out under the condition of dilute hydrochloric acid, and the molar concentration of the dilute hydrochloric acid is 0.5-6.0 mol/liter. 8. The preparation method according to claim 6 or 7, characterized in that: the temperature of the hydrolysis reaction is 4-30°C, and the time is 1-24 hours; The method also includes the steps of extracting and separating the trifluoromethylamine by column chromatography.