Process for the preparation of amino alcohol derivatives

Abstract

A preparation method of amino alcohol derivatives, the present application relates to the field of preparing amino alcohol derivatives by double functionalization of styrene derivatives, and aims to solve the technical problems of complicated steps and low utilization rate of raw materials in the existing synthesis of amino alcohol derivatives.Method: I. under the condition of nitrogen atmosphere and room temperature, the styrene derivative and N-benzamide-2,4,6-triphenylpyridine tetrafluoroborate derivative are dissolved in a mixed solvent containing alkyl alcohol, then a photocatalyst and a Lewis base are added, mixed uniformly, placed under blue LED light for photoreaction, after the reaction is completed, extracted with water and ethyl acetate, the organic phase is collected, the solvent is removed by rotary evaporation, and then separated and purified by silica gel column chromatography.The method can react at normal temperature and pressure, the reaction condition is mild, green and environmental protection, and has the advantages of simple and effective operation, safety, environmental protection, low cost and the like.The present application is used for synthesizing amino alcohol derivatives.

Description

TECHNICAL FIELD

[0001] The present application relates to the field of preparing amino alcohol derivatives by double functionalization of styrene derivatives. BACKGROUND

[0002] Amino alcohol compounds are widely used in the medical field as drugs or drug intermediates. For example, the structure of tert-butyl alcohol is It can be used to relieve the symptoms of asthma and chronic obstructive pulmonary disease, such as coughing, wheezing and difficulty breathing; the structure of paclitaxel is It can be used as an anticancer drug and has been widely used in the treatment of breast cancer, lung cancer and other cancers. Synthesis of amino alcohol compounds has important medical significance and has attracted widespread attention in organic chemistry and medicine. However, there are few methods for synthesizing ortho amino alcohol derivatives at present, and the synthesis steps are complicated, the production cost is high and the yield is low. SUMMARY

[0003] The present application solves the technical problems of complicated synthesis steps and low utilization rate of raw materials of existing amino alcohol derivatives, and provides a preparation method of amino alcohol derivatives. The present application synthesizes ortho amino alcohol compounds by double functionalization of styrene, and effectively synthesizes target products in one step.

[0004] A preparation method of an amino alcohol derivative, specifically as follows:

[0005] I. Under the condition of nitrogen atmosphere and room temperature, the styrene derivative and N-benzamide-2,4,6-triphenylpyridine tetrafluoroborate derivative are dissolved in a mixed solvent containing alkyl alcohol, then a photo catalyst and a Lewis base are added, mixed uniformly to obtain a mixed solution;

[0006] II. The mixed solution obtained in step I is placed under blue LED light for photo reaction, after the reaction is completed, water and ethyl acetate are used for extraction, the organic phase is collected, the solvent is removed by rotary evaporation, and then the product is separated and purified by silica gel column chromatography, the obtained product is an amine alcohol compound after double functionalization of styrene, that is, an amino alcohol derivative, and the preparation is completed.

[0007] Further, the molar ratio of the styrene derivative, N-benzamide-2,4,6-triphenylpyridine tetrafluoroborate derivative, Lewis base and photo catalyst in step I is (20-40):10:(15-20):1.

[0008] Further, the molar volume ratio of the N-benzamide-2,4,6-triphenylpyridine tetrafluoroborate derivative to the mixed solvent containing alkyl alcohol in step I is 1 mol:(5-10) L.

[0009] Further, the chemical structural formula of the styrene derivative in step I is: wherein R 1 is hydrogen (H), tert-butyl (t-Bu), methoxy (OMe), or methyl (Me).

[0010] Further, the chemical structural formula of the N-benzamide-2,4,6-triphenylpyridinium tetrafluoroborate derivative of step one is: wherein R 2 is hydrogen (H), methyl (Me), or methoxy (OMe).

[0011] The reaction formula for the synthesis of the N-benzamide-2,4,6-triphenylpyridinium tetrafluoroborate derivative is:

[0012]

[0013] The synthesis steps are as follows: hydrazine hydrate (3.6 g, 60 mmol) is added to a reaction bottle, along with triethylamine (Et3N, 1.25 eq.) and N,N-dimethyl-4-aminopyridine (DMAP, 0.08 eq.) in the appropriate proportions, and dry dichloromethane is used as the solvent. When the solution is cooled to 0°C, p-methoxybenzoyl chloride (0.8 eq.) is slowly added, and after 30 minutes of reaction, stirring is carried out at room temperature, and the progress of the reaction is monitored by TLC. After the raw materials are completely reacted, the reaction solvent is concentrated by rotary evaporation, and the product, p-methoxybenzoyl hydrazine (5.2 g, yield 80%), is separated by column chromatography. The p-methoxybenzoyl hydrazine (4.1 g, 30 mmol) obtained in the previous step is added to a reaction bottle along with 2,4,6-triphenylpyridinium tetrafluoroborate (1.05 eq.), and ethanol is used as the reaction solvent. The reaction is heated to reflux, and after 4 hours of reaction, the reaction is cooled to room temperature, and ether is slowly added dropwise. White solids slowly precipitate, and the target product, 1-(4-methoxybenzamide)-2,4,6-triphenylpyridinium salt (9.8 g, yield 60%), is obtained after suction filtration.

[0014] Further, the mixed solvent containing an alkyl alcohol in step one is composed of an alkyl alcohol and an organic solvent, and the volume ratio of the alkyl alcohol to the organic solvent is 1:2.

[0015] The chemical structural formula of the alkyl alcohol is R 3 OH, R 3 is methyl (Me), n-propyl (n-Pr), i-propyl (i-Pr), or cyclohexyl (Cy).

[0016] The organic solvent is dichloromethane, acetonitrile, tetrahydrofuran, dioxane, or N,N-dimethylformamide.

[0017] Further, the photocatalyst in step one is fac-Ir(ppy)3, and the chemical structural formula is:

[0018] Further, the Lewis base in step one is sodium tetrafluoroborate.

[0019] The reaction formula of the present application is as follows:

[0020]

[0021] The reaction principle of the present application is as follows:

[0022]

[0023] Firstly, the photocatalyst fac-Ir(ppy)3 is in an excited state under the irradiation of a light source with a wavelength of 450 nm, the excited photocatalyst carries out a single electron transfer process with the substrate pyridine salt 1a, the Ir(III) catalyst is oxidized to form an Ir(IV) species, and the pyridine salt is broken through N-N bond to generate a p-methoxybenzamide free radical, 2,4,6-triphenylpyridine and a tetrafluoroborate negative ion. Subsequently, the amide free radical A carries out a radical addition reaction with the substrate p-methoxy styrene 2a to generate a carbon radical intermediate B. The carbon radical intermediate B can be oxidized by the Ir(IV) catalyst to generate a carbon cation C, and the photocatalyst is oxidized to fac-Ir(ppy)3 to complete the redox cycle of the catalyst. The alcohol as a suitable nucleophile can attack the carbon cation C to obtain the target ortho amino alcohol.

[0024] The present application has the following advantages:

[0025] The present application provides a simple one-step method for synthesizing amino alcohol derivatives, which solves the problems of complicated synthesis steps, low yield and environmental pollution of the existing amino alcohol derivatives. The method can be reacted at normal temperature and pressure, and has the advantages of simple and effective operation, safety, environmental protection and low cost.

[0026] The present application is used for synthesizing amino alcohol derivatives. BRIEF DESCRIPTION OF DRAWINGS

[0027] Figure 1 The H NMR spectrum of N-(2-methoxy-2-(4-methoxyphenyl)ethyl)benzamide prepared for Example 1 is as follows: 1 H NMR spectrum;

[0028] Figure 2 The H NMR spectrum of N-(2-methoxy-2-(4-methoxyphenyl)ethyl)benzamide prepared for Example 1 is as follows: 13 C NMR spectrum;

[0029] Figure 3 The H NMR spectrum of 4-chloro-N-(2-methoxy-2-(4-methoxyphenyl)ethyl)benzamide prepared for Example 2 is as follows: 1 H NMR spectrum;

[0030] Figure 4 HNMR spectrum of 4-methoxy-N-(2-methoxy-2-(4-methoxyphenyl)ethyl)benzamide prepared in Example 3 13 CNMR spectrum;

[0031] Figure 5 HNMR spectrum of 4-methoxy-N-(2-methoxy-2-(4-methoxyphenyl)ethyl)benzamide prepared in Example 3 1 HNMR spectrum;

[0032] Figure 6 HNMR spectrum of 4-methoxy-N-(2-methoxy-2-(4-methoxyphenyl)ethyl)benzamide prepared in Example 3 13 CNMR spectrum;

[0033] Figure 7 HNMR spectrum of 4-methoxy-N-(2-methoxy-2-(4-methoxyphenyl)ethyl)benzamide prepared in Example 3 1 HNMR spectrum;

[0034] Figure 8 HNMR spectrum of 4-methoxy-N-(2-methoxy-2-(4-methoxyphenyl)ethyl)benzamide prepared in Example 3 13 CNMR spectrum;

[0035] Figure 9 HNMR spectrum of N-(2-(4-p-t-butylphenyl)-2-methoxyethyl)-4-methoxybenzamide prepared in Example 5 1 HNMR spectrum;

[0036] Figure 10 HNMR spectrum of N-(2-(4-p-t-butylphenyl)-2-methoxyethyl)-4-methoxybenzamide prepared in Example 5 13 CNMR spectrum;

[0037] Figure 11 HNMR spectrum of N-(2-(4-p-t-butylphenyl)-2-methoxyethyl)-4-methoxybenzamide prepared in Example 5 1 HNMR spectrum;

[0038] Figure 12 HNMR spectrum of N-(2-(4-p-t-butylphenyl)-2-methoxyethyl)-4-methoxybenzamide prepared in Example 5 13 CNMR spectrum;

[0039] Figure 13 HNMR spectrum of 4-methoxy-N-(2-(4-methoxyphenyl)-2-propoxyethyl)benzamide prepared in Example 7 1 HNMR spectrum;

[0040] Figure 14 H NMR spectrum of 4-methoxy-N-(2-(4-methoxyphenyl)-2-propoxyethyl)benzamide prepared in Example 7 13 CNMR spectrum;

[0041] Figure 15 H NMR spectrum of 4-methoxy-N-(2-(4-methoxyphenyl)-2-propoxyethyl)benzamide prepared in Example 7 1 H NMR spectrum of 4-methoxy-N-(2-(4-methoxyphenyl)-2-propoxyethyl)benzamide prepared in Example 7

[0042] Figure 16 H NMR spectrum of 4-methoxy-N-(2-(4-methoxyphenyl)-2-propoxyethyl)benzamide prepared in Example 7 13 CNMR spectrum of 4-methoxy-N-(2-(4-methoxyphenyl)-2-propoxyethyl)benzamide prepared in Example 7

[0043] Figure 17 H NMR spectrum of 4-methoxy-N-(2-(4-methoxyphenyl)-2-propoxyethyl)benzamide prepared in Example 7 1 H NMR spectrum of 4-methoxy-N-(2-(4-methoxyphenyl)-2-propoxyethyl)benzamide prepared in Example 7

[0044] Figure 18 H NMR spectrum of 4-methoxy-N-(2-(4-methoxyphenyl)-2-propoxyethyl)benzamide prepared in Example 7 13 CNMR spectrum of 4-methoxy-N-(2-(4-methoxyphenyl)-2-propoxyethyl)benzamide prepared in Example 7 DETAILED DESCRIPTION

[0045] DETAILED DESCRIPTION

[0046] I. Dissolve the styrene derivative and the N-benzamide-2,4,6-triphenylpyridine tetrafluoroborate derivative in a mixed solvent containing an alkyl alcohol under a nitrogen atmosphere at room temperature, then add a photo-catalyst and a Lewis base, mix uniformly to obtain a mixed solution;

[0047] II. Place the mixed solution obtained in step I under blue LED light for photo-irradiation reaction. After the reaction is completed, extract with water and ethyl acetate, collect the organic phase, remove the solvent by rotary evaporation, and then separate and purify by silica gel column chromatography to obtain the product, which is an amine alcohol compound after the double functionalization of styrene, i.e. an amino alcohol derivative, thus completing the preparation.

[0048] DETAILED DESCRIPTION

[0049] Specific embodiment three: the difference between this embodiment and specific embodiment one or two is that the molar volume ratio of the N-benzamide-2,4,6-triphenylpyridine tetrafluoroborate derivative to the mixed solvent containing alkyl alcohol in step one is 1 mol:(5-10) L. The others are the same as specific embodiment one or two.

[0050] Specific embodiment four: the difference between this embodiment and one of specific embodiments one to three is that the chemical structural formula of the styrene derivative in step one is: wherein R 1 is hydrogen, tert-butyl, methoxy or methyl. The others are the same as one of specific embodiments one to three.

[0051] Specific embodiment five: the difference between this embodiment and one of specific embodiments one to four is that the chemical structural formula of the N-benzamide-2,4,6-triphenylpyridine tetrafluoroborate derivative in step one is: wherein R 2 is hydrogen, methyl or methoxy. The others are the same as one of specific embodiments one to four.

[0052] Specific embodiment six: the difference between this embodiment and one of specific embodiments one to five is that the mixed solvent containing alkyl alcohol in step one is composed of alkyl alcohol and organic solvent, and the volume ratio of alkyl alcohol to organic solvent is 1:2;

[0053] The chemical structural formula of the alkyl alcohol is R 3 OH, R 3 is methyl, n-propyl, isopropyl or cyclohexyl;

[0054] The organic solvent is dichloromethane, acetonitrile, tetrahydrofuran, dioxane or N,N-dimethylformamide. The others are the same as one of specific embodiments one to five.

[0055] Specific embodiment seven: the difference between this embodiment and one of specific embodiments one to six is that the photocatalyst in step one is fac-Ir(ppy)3, and the chemical structural formula is: The others are the same as one of specific embodiments one to six.

[0056] Specific embodiment eight: the difference between this embodiment and one of specific embodiments one to seven is that the Lewis base in step one is sodium tetrafluoroborate. The others are the same as one of specific embodiments one to seven.

[0057] Specific embodiment nine: the difference between this embodiment and one of specific embodiments one to eight is that the time for controlling the reaction under blue LED light irradiation in step two is 8-24 h, and the power of the LED light is 20 W. The others are the same as one of specific embodiments one to eight.

[0058] Specific implementation ten: the difference between this implementation and one of the specific implementations one to nine is that: the solvent used for the silica gel column chromatography separation and purification in step two is a mixed solvent of petroleum ether and ethyl acetate, and the volume ratio of petroleum ether to ethyl acetate is (1-4): 1. The others are the same as one of the specific implementations one to nine.

[0059] The content of the application is not limited to the content of each of the above embodiments, and the combination of one or several specific embodiments can also achieve the purpose of the application.

[0060] Example 1:

[0061] A preparation method of an amino alcohol derivative is carried out in the following steps:

[0062] Into a 10 mL photo reaction tube, p-methoxy styrene (0.4 mmol), N-benzamide-2,4,6-triphenylpyridine tetrafluoroborate (0.1 mmol), sodium tetrafluoroborate (0.2 mmol), fac-Ir (ppy) 3 (0.005 mmol), super dry methanol (0.3 mL) and dry dichloromethane (0.6 mL) were added in turn, and oxygen was removed by bubbling with a nitrogen ball for 0.5 h; then, the reaction system was sealed and irradiated under a blue LED lamp with a power of 20 W for 12 h. After the reaction was completed, the organic solvent was concentrated and dried by a rotary evaporator, and then a mixed solution of petroleum ether and ethyl acetate with a volume ratio of 4:1 was used as an eluent to carry out silica gel column chromatography purification and separation, to obtain N-(2-methoxy-2-(4-methoxyphenyl) ethyl) benzamide, and the structural formula is:

[0063]

[0064] Purity 99%. Yield 72%. Its nuclear magnetic resonance data are: 1 H NMR (400 MHz, Chloroform-d) δ 7.77 (dd, J = 6.9, 1.6 Hz, 2H), 7.50 (t, J = 7.3 Hz, 1H), 7.44 (t, J = 7.4 Hz, 2H), 7.27 (d, J = 8.8 Hz, 2H), 6.92 (d, J = 8.6 Hz, 2H), 6.60 (s, 1H), 4.33 (dd, J = 8.9, 4.0 Hz, 1H), 3.89 (ddd, J = 13.8, 7.7, 4.0 Hz, 1H), 3.82 (s, 3H), 3.39 (ddd, J = 13.8, 8.9, 3.9 Hz, 1H), 3.25 (s, 3H).

[0065] 13C NMR (101 MHz, CDCI3) δ 167.5, 159.8, 134.8, 131.7, 131.2, 128.8, 128.1, 127.1, 114.2, 82.0, 56.8, 55.5, 46.3.

[0066] Example 2:

[0067] A method for preparing an amino alcohol derivative is carried out according to the following steps:

[0068] Into a 10 mL photo reaction tube, p-methoxystyrene (0.4 mmol), N-(4- methylbenzamide)-2,4,6-triphenylpyridinium tetrafluoroborate (0.1 mmol), sodium tetrafluoroborate (0.2 mmol), fac-Ir(ppy)3(0.005 mmol), super dry methanol (0.3 mL) and dry dichloromethane (0.6 mL) were added successively, and oxygen was removed by bubbling with a nitrogen balloon for 0.5 h; then, the reaction system was sealed and irradiated under a blue LED lamp with a power of 20 W for 12 h. After the reaction was completed, the organic solvent was concentrated and dried by a rotary evaporator, and then a mixed solution of petroleum ether and ethyl acetate with a volume ratio of 4:1 was used as an eluent to purify and separate by silica gel column chromatography to obtain 4-chloro-N-(2-methoxy-2-(4-methoxyphenyl)ethyl)benzamide, and its structural formula is:

[0069]

[0070] Purity 99%. Yield 57%. Its nuclear magnetic resonance data are: 1 H NMR (400 MHz, Chloroform-d) δ 7.74 (d, J = 8.8 Hz, 2H), 7.26-7.16 (m, 4H), 6.93 (d, J = 8.8 Hz, 2H), 6.49 (s, 1H), 4.34 (dd, J = 8.9, 3.9 Hz, 1H), 3.95-3.85 (m, 4H), 3.36 (ddd, J = 13.4, 8.9, 3.9 Hz, 1H), 3.27 (s, 3H), 2.36 (s, 3H). 13 C NMR (101 MHz, CDCI3) δ 167.1, 162.4, 138.2, 136.3, 129.5, 129.0, 127.1, 126.9, 113.9, 82.5, 57.0, 55.6, 46.3, 21.4.

[0071] Example 3:

[0072] A method for preparing an amino alcohol derivative is carried out according to the following steps:

[0073] Into a 10 mL photo reaction tube, p-methoxystyrene (0.4 mmol), N-(4-methoxybenzamido)-2,4,6-triphenylpyridinium tetrafluoroborate (0.1 mmol), sodium tetrafluoroborate (0.2 mmol), fac-Ir(ppy)3(0.005 mmol), super dry methanol (0.3 mL) and dry dichloromethane (0.6 mL) were added successively, and deoxygenated with a nitrogen balloon for 0.5 h; then, the reaction system was sealed and irradiated under a blue LED lamp with a power of 20 W for 12 h. After the reaction was completed, extraction was performed with ethyl acetate and water, the organic phase was collected, and the organic solvent was concentrated and dried by a rotary evaporator. Then, a mixture of petroleum ether and ethyl acetate with a volume ratio of 4:1 was used as an eluent to perform silica gel column chromatography purification and separation, to obtain 4-methoxy-N-(2-methoxy-2-(4-methoxyphenyl)ethyl)benzamide, and its structural formula is:

[0074]

[0075] Purity 99%. Yield 67%. Its NMR data are as follows: 1 H NMR (400 MHz, Chloroform-d) δ 7.74 (d, J = 8.8 Hz, 2H), 7.27 (d, J = 7.3 Hz, 2H), 6.92 (m, 4H), 6.51 (s, 1H), 4.32 (dd, J = 8.9, 4.0 Hz, 1H), 3.91-3.86 (m, 1H), 3.85 (s, 3H), 3.82 (s, 3H), 3.37 (ddd, J = 13.8, 8.8, 3.9 Hz, 1H), 3.25 (s, 3H).

[0076] 13 C NMR (101 MHz, CDCl3) δ 167.1, 162.3, 159.7, 131.3, 128.9, 128.1, 127.0, 114.2, 113.9, 82.1, 56.8, 55.6, 55.5, 46.2.

[0077] Example 4:

[0078] A preparation method of an amino alcohol derivative is performed according to the following steps:

[0079] Into a 10 mL photo reaction tube, styrene (0.4 mmol), N-(4-methoxybenzamide)-2,4,6-triphenylpyridinium tetrafluoroborate (0.1 mmol), sodium tetrafluoroborate (0.2 mmol), fac-Ir(ppy)3(0.005 mmol), super dry methanol (0.3 mL) and dry dichloromethane (0.6 mL) were added successively, and deoxygenated by bubbling with a nitrogen balloon for 0.5 h; then, the reaction system was sealed and irradiated under a blue LED lamp with a power of 20 W for 12 h. After the reaction was completed, extraction was performed with ethyl acetate and water, the organic phase was collected, and the organic solvent was concentrated and dried by a rotary evaporator. Then, a mixture of petroleum ether and ethyl acetate with a volume ratio of 4:1 was used as an eluent to perform silica gel column chromatography purification and separation, to obtain 4-methoxy-N-(2-methoxy-2-phenylethyl)benzamide, and its structural formula is:

[0080]

[0081] Purity 99%. Yield 60%. Its nuclear magnetic resonance data are: 1 H NMR (400 MHz, Chloroform-d) δ 7.75 (d, J = 6.3 Hz, 2H), 7.42-7.31 (m, 5H), 6.94 (d, J = 6.3 Hz, 2H), 6.53 (s, 1H), 4.38 (dd, J = 8.9, 3.5 Hz, 1H), 3.96-3.89 (m, 1H), 3.85 (s, 3H), 3.37 (ddd, J = 13.4, 8.7, 3.5 Hz, 1H), 3.28 (s, 3H). 13 C NMR (101 MHz, CDCl3) δ 167.1, 162.4, 139.3, 129.0, 128.8, 128.4, 126.9, 114.0, 113.9, 82.6, 57.1, 55.6, 46.3.

[0082] Example 5:

[0083] A preparation method of an amino alcohol derivative is performed according to the following steps:

[0084] Into a 10 mL photo reaction tube, p-tert-butylstyrene (0.4 mmol), N-(4-methoxybenzamido)-2,4,6-triphenylpyridinium tetrafluoroborate (0.1 mmol), sodium tetrafluoroborate (0.2 mmol), fac-Ir(ppy)3(0.005 mmol), super dry methanol (0.3 mL) and dry dichloromethane (0.6 mL) were added successively, and deoxygenated with a nitrogen balloon for 0.5 h; then, the reaction system was sealed and irradiated under a blue LED lamp with a power of 20 W for 12 h. After the reaction was completed, extraction was performed with ethyl acetate and water, the organic phase was collected, and the organic solvent was concentrated and dried by a rotary evaporator. Then, a mixture of petroleum ether and ethyl acetate with a volume ratio of 4:1 was used as an eluent to perform silica gel column chromatography to purify and separate N-(2-(4-p-tert-butylphenyl)-2-methoxyethyl)-4-methoxybenzamide, and the structural formula thereof is as follows:

[0085]

[0086] Purity 99%. Yield 62%. Its nuclear magnetic resonance data: 1 H NMR (400 MHz, Chloroform-d) δ 7.74 (d, J = 8.7 Hz, 2H), 7.40 (d, J = 8.1 Hz, 2H), 7.27 (d, J = 8.9 Hz, 2H), 6.93 (d, J = 8.7 Hz, 2H), 6.52 (s, 1H), 4.35 (dd, J = 9.0, 3.9 Hz, 1H), 3.92 (ddd, J = 13.7, 7.8, 3.9 Hz, 1H), 3.85 (s, 3H), 3.35 (ddd, J = 13.4, 8.9, 3.8 Hz, 1H), 3.28 (s, 3H), 1.33 (s, 9H).

[0087] 13 C NMR (101 MHz, CDCl3) δ 167.1, 162.3, 151.3, 136.2, 129.0, 127.1, 126.6, 125.7, 113.9, 82.4, 57.1, 55.6, 46.2, 34.8, 31.6.

[0088] Example 6:

[0089] A preparation method of an amino alcohol derivative is performed according to the following steps:

[0090] Into a 10 mL photo-reactor tube, p-methylstyrene (0.4 mmol), N-(4- methoxybenzamide)-2,4,6-triphenylpyridinium tetrafluoroborate (0.1 mmol), sodium tetrafluoroborate (0.2 mmol), fac-Ir(ppy)3(0.005 mmol), super dry methanol (0.3 mL) and dry dichloromethane (0.6 mL) were added successively, and deoxygenated with a nitrogen balloon for 0.5 h; then, the reaction system was sealed and irradiated under a blue LED lamp with a power of 20 W for 12 h. After the reaction was completed, extraction was performed with ethyl acetate and water, the organic phase was collected, and the organic solvent was concentrated and dried by a rotary evaporator. Then, a mixed solution of petroleum ether and ethyl acetate with a volume ratio of 1:1 was used as an eluent to perform silica gel column chromatography purification and separation, to obtain N-(2-(4-p-tolyl)-2-methoxyethyl)-4-methoxybenzamide, and its structural formula is:

[0091]

[0092] Purity 99%. Yield 52%. Its NMR data are as follows: 1 H NMR (400 MHz, Chloroform-d) δ 7.74 (d, J = 8.8 Hz, 2H), 7.26-7.18 (m, 4H), 6.93 (d, J = 8.8 Hz, 2H), 6.50 (s, 1H), 4.34 (dd, J = 8.8, 3.9 Hz, 1H), 3.95-3.85 (m, 1H), 3.85 (s, 3H), 3.36 (ddd, J = 13.4, 8.9, 3.9 Hz, 1H), 3.27 (s, 3H), 2.36 (s, 3H).

[0093] 13 C NMR (101 MHz, CDCl3) δ 167.0, 162.4, 138.1, 136.3, 129.5, 129.0, 127.1, 126.9, 113.9, 82.5, 57.0, 55.6, 46.2, 21.4.

[0094] Example 7:

[0095] A preparation method of an amino alcohol derivative is performed according to the following steps:

[0096] Into a 10 mL photo-reactor tube, p-methoxystyrene (0.4 mmol), N-(4-methoxybenzamide)-2,4,6-triphenylpyridinium tetrafluoroborate (0.1 mmol), sodium tetrafluoroborate (0.2 mmol), fac-Ir(ppy)3(0.005 mmol), ultra-dry n-propanol (0.3 mL) and dry dichloromethane (0.6 mL) were added successively, and deoxygenated by bubbling with a nitrogen balloon for 0.5 h; then, the reaction system was sealed and irradiated under a blue LED lamp with a power of 20 W for 12 h. After the reaction was completed, extraction was performed with ethyl acetate and water, the organic phase was collected, and the organic solvent was concentrated and dried by a rotary evaporator. Then, a mixture of petroleum ether and ethyl acetate with a volume ratio of 4:1 was used as an eluent to perform silica gel column chromatography to purify and separate, to obtain 4-methoxy-N-(2-(4-methoxyphenyl)-2-propyloxyethyl)benzamide, and its structural formula is:

[0097]

[0098] Purity 99%. Yield 67%. Its nuclear magnetic resonance data are: 1 H NMR (400 MHz, Chloroform-d) δ 7.73 (d, J = 8.6 Hz, 2H), 7.28 (d, J = 8.6 Hz, 2H), 6.95-6.89 (m, 4H), 6.56 (s, 1H), 4.42 (dd, J = 9.0, 4.0 Hz, 1H), 3.91-3.86 (m, 1H), 3.85 (s, 3H), 3.81 (s, 3H), 3.39-3.32 (m, 2H), 3.28-3.22 (m, 1H), 1.63-1.56 (m, 2H), 0.91 (t, J = 7.3 Hz, 3H).

[0099] 13 C NMR (101 MHz, CDCl3) δ 167.0, 162.3, 159.6, 132.0, 128.9, 128.0, 127.1, 114.2, 114.0, 80.3, 70.7, 55.6, 55.5, 46.4, 23.2, 10.9.

[0100] Example 8:

[0101] A preparation method of an amino alcohol derivative is performed according to the following steps:

[0102] Into a 10 mL photo-reactor tube, p-methoxystyrene (0.4 mmol), N-(4-methoxybenzamide)-2,4,6-triphenylpyridinium tetrafluoroborate (0.1 mmol), sodium tetrafluoroborate (0.2 mmol), fac-Ir(ppy)3(0.005 mmol), super-dry isopropanol (0.3 mL) and dry dichloromethane (0.6 mL) were added successively, and deoxygenated with a nitrogen balloon for 0.5 h; then, the reaction system was sealed and irradiated under a blue LED lamp with a power of 20 W for 12 h. After the reaction was completed, extraction was performed with ethyl acetate and water, the organic phase was collected, and the organic solvent was concentrated and dried by a rotary evaporator. Then, a mixture of petroleum ether and ethyl acetate with a volume ratio of 4:1 was used as an eluent to perform silica gel column chromatography to purify and separate, to obtain 4-methoxy-N-(2-(4-methoxyphenyl)-2-isopropoxyethyl)benzamide, and its structural formula is:

[0103]

[0104] Purity 99%. Yield 53%. Its NMR data are as follows: 1 H NMR (400 MHz, Chloroform-d) δ 7.73 (d, J = 8.6 Hz, 2H), 7.30 (d, J = 6.7 Hz, 1H), 7.00-6.82 (m, 4H), 6.54 (s, 2H), 4.58-4.52 (m, 1H), 3.91-3.83 (m, 4H), 3.82 (s, 3H), 3.61-3.50 (m, 1H), 3.32-3.21 (m, 1H), 1.13 (dd, J = 10.9, 6.0 Hz, 6H).

[0105] 13 C NMR (101 MHz, CDCl3) δ 167.1, 162.4, 159.6, 132.7, 128.8, 128.0, 127.1, 114.1, 114.0, 76.9, 69.4, 55.6, 55.5, 46.6, 23.6, 21.6.

[0106] Example 9:

[0107] A preparation method of an amino alcohol derivative is performed according to the following steps:

[0108] Into a 10 mL photo reaction tube, p-methoxystyrene (0.4 mmol), N-(4-methoxybenzamide)-2,4,6-triphenylpyridinium tetrafluoroborate (0.1 mmol), sodium tetrafluoroborate (0.2 mmol), fac-Ir(ppy)3(0.005 mmol), super dry cyclohexanol (0.3 mL) and dry dichloromethane (0.6 mL) were added successively, and deoxygenated with a nitrogen balloon for 0.5 h; then, the reaction system was sealed and irradiated under a blue LED lamp with a power of 20 W for 12 h. After the reaction was completed, extraction was performed with ethyl acetate and water, the organic phase was collected, and the organic solvent was concentrated and dried by a rotary evaporator. Then, a mixture of petroleum ether and ethyl acetate with a volume ratio of 4:1 was used as an eluent to purify and separate the product by silica gel column chromatography to obtain N-(2-cyclohexyloxy)-2-(4-methoxyphenyl)ethyl)-4-methoxybenzamide, and its structural formula is:

[0109]

[0110] Purity 99%. Yield 42%. Its NMR data are as follows: 1 H NMR (400 MHz, Chloroform-d) δ 7.74 (d, J = 8.8 Hz, 2H), 7.30 (d, J = 8.6 Hz, 2H), 6.96-6.88 (m, 4H), 6.60 (s, 1H), 4.60 (dd, J = 9.2, 3.8 Hz, 1H), 3.91-3.86 (m, 1H), 3.85 (s, 3H), 3.81 (s, 3H), 3.30-3.20 (m, 2H), 1.76-1.63 (m, 4H), 1.30-1.24 (m, 3H), 1.20-1.13 (m, 3H).

[0111] 13 C NMR (101 MHz, CDCl3) δ 167.0, 162.3, 159.5, 132.9, 128.8, 128.0, 127.1, 114.1, 114.0, 75.4, 55.6, 55.5, 46.6, 33.8, 31.8, 25.9, 24.4, 24.2.

Claims

1. A process for the preparation of an amino alcohol derivative, characterized by The method is specifically performed according to the following steps: I. The styrene derivative and the Lewis base are dissolved in a mixed solvent containing an alkyl alcohol under a nitrogen atmosphere at room temperature to obtain a mixed solution; the chemical structural formula of the alkyl alcohol is R 3 OH, R 3 is methyl, n-propyl, isopropyl, or cyclohexyl. II. The mixed solution is irradiated with light to obtain a benzamide-2,4,6-triphenylpyridine tetrafluoroborate derivative. N III. The benzamide-2,4,6-triphenylpyridine tetrafluoroborate derivative is separated and purified to obtain a benzamide-2,4,6-triphenylpyridine tetrafluoroborate derivative with a high yield. II. The mixed solution obtained in step I is subjected to photoreaction under blue LED light, and after the reaction is completed, water and ethyl acetate are used for extraction, the organic phase is collected, and after the solvent is removed by rotary evaporation, the product is separated and purified by silica gel column chromatography to obtain a styrene bifunctional amine alcohol compound, i.e. an amino alcohol derivative, thereby completing the preparation; The chemical structural formula of the styrene derivative in step one is: wherein R 1 is hydrogen, tert-butyl, methoxy or methyl; as described in step one N - the chemical structure of the benzamide-2,4,6-triphenylpyridinium tetrafluoroborate derivative is: wherein R 2 is hydrogen, methyl or methoxy; The photocatalyst of step one is fac - Ir(ppy)3, chemical structural formula is: The Lewis base in step I is sodium tetrafluoroborate.

2. The process for the preparation of amino alcohol derivatives according to claim 1, characterized in that a styrene derivative as described in step one, N - the molar ratio of the benzamide-2,4,6-triphenylpyridinium tetrafluoroborate derivative, the Lewis base and the photocatalyst is (20-40) : 10 : (15-20) :

1.

3. The method for preparing an amino alcohol derivative according to claim 1, characterized in that as described in step one N - The molar volume ratio of the benzamide-2,4,6-triphenylpyridine tetrafluoroborate derivative to the mixed solvent containing an alkyl alcohol is 1 mol : (5-10) L.

4. The method for preparing an amino alcohol derivative according to claim 1, characterized in that The mixed solvent containing alkyl alcohol in step I is composed of alkyl alcohol and an organic solvent, and the volume ratio of alkyl alcohol to organic solvent is 1:

2. The organic solvent is dichloromethane, acetonitrile, tetrahydrofuran, dioxane or N,N dimethylformamide.

5. The method for preparing an amino alcohol derivative according to claim 1, characterized in that The time for irradiation reaction of blue LED light in step II is 8-24 h, and the power of LED light is 20 W.

6. The method for preparing an amino alcohol derivative according to claim 1, characterized in that The solvent used for separation and purification by silica gel column chromatography in step II is a mixed solvent of petroleum ether and ethyl acetate, and the volume ratio of petroleum ether to ethyl acetate is (1-4):1.

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