阅读说明：本技术 5-氟烷基取代噁唑化合物的制备方法 (Preparation method of 5-fluoroalkyl substituted oxazole compound ) 是由 李滨 江涤 王佰全 于 2021-09-30 设计创作，主要内容包括：5-氟烷基取代噁唑化合物的制备方法。本发明公开了5-氟烷基取代噁唑化合物的制备方法,该方法包括通过氟烷基取代重氮酮与伯酰胺在六氟磷酸四乙氰铜条件下催化环化,得到相应的5-氟烷基取代噁唑化合物。本方法的有益效果是：制备方法工艺简单、反应温度较温和、产率高、原料和催化剂廉价易得。(A preparation method of a 5-fluoroalkyl substituted oxazole compound. The invention discloses a preparation method of a 5-fluoroalkyl substituted oxazole compound, which comprises the step of carrying out catalytic cyclization on fluoroalkyl substituted diazoketone and primary amide under the condition of copper tetraethyl hexafluorophosphate to obtain the corresponding 5-fluoroalkyl substituted oxazole compound. The method has the beneficial effects that: the preparation method has the advantages of simple process, mild reaction temperature, high yield, and cheap and easily-obtained raw materials and catalysts.)

1. a preparation method of a 5-fluoroalkyl substituted oxazole compound is characterized in that the chemical structure general formula of the 5-fluoroalkyl substituted oxazole compound is (I):

(I) in the formula: r¹Is aliphatic substituent, aromatic substituent, methoxy-containing substituent, nitro-group, cyano-group, trifluoromethyl, methyl, various halogens and benzene ring substituent substituted by oxygen-containing heterocycle; r²Is an aliphatic substituent, a heterocyclic substituent, an olefin substituent, an aromatic substituent, a methoxyl-containing substituent, halogen, alkenyl, an oxygen-containing heterocyclic ring and a benzene ring substituent containing condensed ring substitution; r¹，R²May be the same or different; r_fTrifluoromethyl, pentafluoroethyl and heptafluoropropyl;

the preparation method comprises the following steps:

step 1, fluoroalkyl-substituted diazoketone, primary amide and copper tetraethyl hexafluorophosphate are added into a reaction tube which is dried in advance and is filled with magnetons, and the mixture is uniformly mixed;

step 2, pumping the gas for three times, adding dry 1, 2-dichloroethane (2mL) in the argon atmosphere, and hermetically placing the reaction tube in a preheated oil bath at 100-110 ℃ for reaction for 16 hours;

and 3, cooling the reaction liquid obtained in the step 2 to room temperature, adding dichloromethane, transferring the mixture into a round-bottom bottle, removing the solvent by using a rotary evaporator, and passing through a silica gel column to obtain the colorless solid or oily target 5-fluoroalkyl substituted oxazole compound.

2. A method for producing a 5-fluoroalkyl substituted oxazole compound according to claim 1, wherein: the fluoroalkyl-substituted diazoketone is a diazo compound with different acyl groups and fluoroalkyl groups, wherein the substituent group on the acyl group comprises an aliphatic substituent group, an aromatic substituent group, a methoxyl-containing group, a nitro group, a cyano group, a trifluoromethyl group, a methyl group, various halogens and an oxygen-containing heterocyclic ring substituted benzene ring substituent group, and the fluoroalkyl group comprises a trifluoromethyl group, a pentafluoroethyl group and a heptafluoropropyl group.

3. A method for producing a 5-fluoroalkyl substituted oxazole compound according to claim 1, wherein: the primary amide is an amide compound with different acyl substituents, and the substituents on the acyl include aliphatic substituents, heterocyclic substituents, olefin substituents, aromatic substituents, methoxy-containing substituents, halogen, alkenyl, oxygen-containing heterocyclic rings and fused ring-containing substituted benzene ring substituents.

4. A method for producing a 5-fluoroalkyl substituted oxazole compound according to claim 1, wherein: the molar ratio of the primary amide to the fluoroalkyl-substituted diazoketone to the copper tetrakishexafluorophosphate is 0.2: 0.4: 0.01.

5. a method for producing a 5-fluoroalkyl substituted oxazole compound according to claim 1, wherein: the dosage ratio of the 1, 2-dichloroethane to the primary amide is 2 mL: 0.2 mmol.

6. A5-fluoroalkyl substituted oxazole compound prepared by the process of any one of claims 1 to 5.

Technical Field

The invention relates to a preparation method of a 5-fluoroalkyl substituted oxazole compound, belonging to the fields of biological pharmacy and material science.

Background

Oxazole compounds are important heterocyclic compounds with biological activity, which are widely applied to the field of biological pharmacy and also have important application in the field of material science, and refer to: 1) falorn, m.; giatomelli, g.; porcheddu, a.; dettori, g.eur.j.org.chem.2000,2000, 3217-3222; 2) jin, Z.Nat.Prod.Rep.2011,28,1143-1191.

The introduction of fluorine-containing groups into organic functional molecules can change the chemical, physical and biological properties of the original functional molecules, such as solubility, lipophilicity, conformation and the like. Introduction of fluorine atoms or fluorinated groups into biologically active molecules has become an investigation in pharmaceutical chemistry and material chemistryThe new medicine and material molecules have very popular research strategies, especially in the field of pesticide molecule development. Fluoroalkyl-substituted heterocycles are ubiquitous in many pharmaceuticals, agrochemicals and functional materials due to their remarkable physical, chemical and biological activity, see: 3) muller, K.; faeh, c.; diederich, F.science.2007,317, 1881-1886; 4) wang, j.; s a nchez-Rosell, M.;J,L.；Pozo,C,del.；Sorochinsky,A,E.；Fustero,S.；Soloshonok,V,A.；Liu,H.Chem.Rev.2014,114,2432-2506；5)Purser,S.；Moore,P,R.；Swallow,S.；Gouverneur,V.Chem.Soc.Rev.2008,37,320-330；6)llardi,E,A.；Vitaku,E.；Njardarson,J,T.J.Med.Chem.2014,57,2832-2842；7)Gillis,E,P.；Eastman,K,J.；Hill,M,D.；Donnelly,D,J.；Meanwell,N,A.J.Med.Chem.2015,58,8315-8359。

although fluorine-containing organic molecules are very useful, fluorine-containing organic compounds are scarcely present in nature. The fluorine-containing groups need to be installed into the designed molecule by different fluorinating agents to obtain the corresponding organic fluorine-containing compounds, see: 8) yang, x.; wu, t.; philips, r.j.; tose, F.D.chem.Rev.2015,115, 826-870; 9) alonso, c.; martini de Marigorta, E.; rubiales, g.; palacios, F.chem.Rev.2015,115, 1847-1935; 10) zuo, z.; zhang, w.; wang, y.; pan, Y.Org.chem.Front.2021,8, 2786-2798; 11) xiao, h.; zhang, z.; fang, y.; zhu, l.; li, C.chem.Soc.Rev.2021,50, 6308-6319. The development of efficient, practical methods for the preparation of fluorine-containing heterocyclic compounds using readily available fluorine-containing synthetic building blocks remains an urgent and challenging endeavor.

Diazo compounds are important building blocks in synthetic organic chemistry due to their diverse reactivity. Recently, fluoro diazo compounds have been synthesized as fluoro building blocks through a series of chemical transformations such as X-H (X ═ C, O, N, Si, S and P) bond insertion, cyclopropenylation, cycloaddition, ylide formation and other metal carbene reactions, see: 12) brahms, d.l.s.; dailey, W.P.chem.Rev.1996,96, 1585-1632; 13) mertens, l.; koenigs, R.M.org.Biomol.Chem.2016,14, 10547-10556; 14) wang, x.; wang, x.; wang, j.tetrahedron,2019,75, 949-; 15) mykhailuk, p.k.; koenigs, R.M.chem.Eur.J.2019,25, 6053-6063; 16) mykhaliniuk, P.K. chem.Rev.2020,120, 12718-12755.

The synthesis route of 5-trifluoromethyl substituted oxazole is very limited, and there are also problems that harsh reaction conditions are required, the substrate range is relatively narrow, and the like, see: 17) wang, y.; zhu, S.J.Fluor.chem.2000,103, 139-144; 18) tsai, Y. -L.; fan, y. -s.; lee, c. -j.; huang, C. -H.; das, u.; lin, w.chem.commun.2013,49, 10266-10268; 19) kawase, m.; miyamae, h.; kurihara, T.chem.Pharm.Bull.1998,46, 749-756. No report of synthesizing 5-fluoroalkyl substituted oxazole compound by using transition metal to catalyze the reaction of fluoroalkyl substituted diazoketone and primary amide exists so far.

Therefore, we disclose here the results of research on the preparation of a series of 5-fluoroalkyl substituted oxazole compounds.

Disclosure of Invention

The invention aims to solve the technical analysis and problems, and provides a method for preparing a 5-fluoroalkyl substituted oxazole compound by catalyzing fluoroalkyl substituted diazoketone and primary amide with copper tetraethyl hexafluorophosphate in one step.

Technical scheme of the invention

A5-fluoroalkyl substituted oxazole compound having the general chemical structure of (I):

R¹is aliphatic substituent, aromatic substituent, methoxy-containing substituent, nitro-group, cyano-group, trifluoromethyl, methyl, various halogens and benzene ring substituent substituted by oxygen-containing heterocycle; r²Is an aliphatic substituent, a heterocyclic substituent, an olefin substituent, an aromatic substituent, a methoxyl-containing substituent, halogen, alkenyl, an oxygen-containing heterocyclic ring and a benzene ring substituent containing condensed ring substitution; r¹，R²May be the same or different; r_fTrifluoromethyl, pentafluoroethyl and heptafluoropropyl.

The preparation method of the 5-fluoroalkyl substituted oxazole comprises the following steps:

step 1, adding fluoroalkyl substituted diazoketone (0.4mmol), primary amide (0.2mmol) and copper tetrakishexafluorophosphate (0.0.01mmol) into a reaction tube which is dried in advance and is provided with magnetons, and uniformly mixing;

step 2, pumping the gas for three times, adding dry 1, 2-dichloroethane (2mL) in the argon atmosphere, and hermetically placing the reaction tube in a preheated oil bath at 100-110 ℃ for reaction for 16 hours;

and 3, cooling the reaction liquid obtained in the step 2 to room temperature, adding dichloromethane, transferring the mixture into a round-bottom bottle, removing the solvent by using a rotary evaporator, and passing through a silica gel column to obtain the colorless solid or oily target 5-fluoroalkyl substituted oxazole compound.

The fluoroalkyl-substituted diazoketone is a diazo compound with different acyl groups and fluoroalkyl groups, wherein the substituent group on the acyl group comprises an aliphatic substituent group, an aromatic substituent group, a methoxyl-containing group, a nitro group, a cyano group, a trifluoromethyl group, a methyl group, various halogens and an oxygen-containing heterocyclic ring substituted benzene ring substituent group, and the fluoroalkyl group comprises a trifluoromethyl group, a pentafluoroethyl group and a heptafluoropropyl group.

The primary amide is an amide compound with different acyl substituents, and the substituents on the acyl include aliphatic substituents, heterocyclic substituents, olefin substituents, aromatic substituents, methoxy-containing substituents, halogen, alkenyl, oxygen-containing heterocyclic rings and fused ring-containing substituted benzene ring substituents.

The molar ratio of the primary amide to the fluoroalkyl-substituted diazoketone to the copper tetrakishexafluorophosphate is 0.2: 0.4: 0.01.

the dosage ratio of the 1, 2-dichloroethane to the primary amide is 2 mL: 0.2 mmol.

The invention also provides the 5-fluoroalkyl substituted oxazole compound prepared by the method.

The invention has the advantages and beneficial effects that:

the preparation method of the fluoroalkyl-substituted oxazole compound provided by the invention has the advantages of simple process, mild reaction temperature, high yield, cheap and easily-obtained raw materials and catalysts, and can be used for preparing various fluoroalkyl-substituted oxazole compounds so as to expand the application of the fluoroalkyl-substituted oxazole compounds in medicines and materials.

Drawings

FIG. 1 is a schematic diagram of a synthetic route of fluoroalkyl-substituted oxazoles.

Detailed Description

The outstanding substantive features and the remarkable effects of the present invention can be seen from the following examples, which are not intended to limit the present invention in any way.

Example 1: preparation of 2, 4-diphenyl-5- (trifluoromethyl) oxazole (compound 1)

Adding 0.4mmol of 2-diazo-3, 3, 3-trifluoro-1-phenylpropane-1-one, 0.2mmol of benzamide and 0.01mmol of copper hexachloro-tetraacetate into a Schlenk reaction tube which is pre-dried and is provided with 50mL of magnetons, and uniformly mixing; after the gas is pumped and exchanged for three times, 2mL of anhydrous 1, 2-dichloroethane is added under the argon atmosphere, and the reaction tube is sealed and placed in a preheated oil bath at 100-110 ℃ for reaction for 16 hours; the reaction solution obtained above is cooled to room temperature, dichloromethane is added to the reaction solution, the mixture is transferred to a round bottom bottle, the solvent is removed by a rotary evaporator, and the mixture is passed through a silica gel column eluent (petroleum ether: ethyl acetate, 50: 1) to obtain a white solid target compound. The yield was 98%. Compound 1 is a known compound, and the nuclear magnetic hydrogen spectrum, nuclear magnetic carbon spectrum, nuclear magnetic fluorine spectrum, high-resolution mass spectrum and melting point are shown in Tsai, Y. -L.; fan, y. -s.; lee, c. -j.; huang, C. -H.; das, u.; lin, w.chem.Commun.2013,49, 10266-10268.

Example 2: preparation of 4- (4-bromophenyl) -2-phenyl-5- (trifluoromethyl) oxazole (compound 2)

The preparation method is the same as example 1. 1- (4-bromophenyl) -2-diazo-3, 3, 3-trifluoropropane-1-ketone is used for replacing 2-diazo-3, 3, 3-trifluoro-1-phenylpropane-1-ketone to obtain a white solid target compound. The yield was 99%. Compound 2 is a known compound, and the nuclear magnetic hydrogen spectrum, nuclear magnetic carbon spectrum, nuclear magnetic fluorine spectrum, high-resolution mass spectrum and melting point are shown in Tsai, Y. -L.; fan, y. -s.; lee, c. -j.; huang, C. -H.; das, u.; lin, w.chem.Commun.2013,49, 10266-10268.

EXAMPLE 34 preparation of- (4-methoxyphenyl) -2-phenyl-5- (trifluoromethyl) oxazole (Compound 3)

The preparation method is the same as example 1. 1- (4-methoxyphenyl) -2-diazo-3, 3, 3-trifluoropropane-1-ketone is used for replacing 2-diazo-3, 3, 3-trifluoro-1-phenylpropane-1-ketone, and a white solid target compound is obtained. The yield was 98%. Compound 3 is a known compound, and the nuclear magnetic hydrogen spectrum, nuclear magnetic carbon spectrum, nuclear magnetic fluorine spectrum, high-resolution mass spectrum and melting point are shown in Tsai, Y. -L.; fan, y. -s.; lee, c. -j.; huang, C. -H.; das, u.; lin, w.chem.Commun.2013,49, 10266-10268.

EXAMPLE 4 preparation of 4- (2-chlorophenyl) -2-phenyl-5- (trifluoromethyl) oxazole (Compound 4)

The preparation method is the same as example 1. 1- (2-chlorphenyl) -2-diazo-3, 3, 3-trifluoropropane-1-ketone is used for replacing 2-diazo-3, 3, 3-trifluoro-1-phenylpropane-1-ketone, and the target compound is obtained as colorless oil. The yield was 87%.¹H NMR(CDCl₃,400MHz):δ8.15(d,J＝7.7Hz,2H),7.58-7.49(m,4H),7.49-7.33(m,3H)；¹³C{¹H}NMR(CDCl₃,100MHz):δ162.2,139.8(q,J＝2.4Hz),135.5(q,J＝42.4Hz),133.9,131.8,131.5,130.9,129.9,129.0,128.8,127.2,126.7,125.9,119.1(q,J＝268.4Hz)；¹⁹F NMR(CDCl₃,376MHz):δ-62.1；HRMS(MALDI):324.0397(C₁₆H₉ClF₃NO,[M+H]⁺).

Example 5 preparation of 4- (4-Nitrophenyl) -2-phenyl-5- (trifluoromethyl) oxazole (Compound 5)

The preparation method is the same as example 1. 1- (4-nitrophenyl) -2-diazo-3, 3, 3-trifluoropropane-1-ketone is used for replacing 2-diazo-3, 3, 3-trifluoro-1-phenylpropane-1-ketone, and a white solid target compound is obtained. The yield was 98%. And Mp: 125 ℃ and 127 ℃.¹H NMR(CDCl₃,400MHz):δ8.46-8.29(m,2H),8.25-8.12(m,2H),7.97(d,J＝8.8Hz,2H),7.65-7.49(m,3H)；¹³C{¹H}NMR(CDCl₃,100MHz):δ162.2,148.3,140.2(q,J＝2.7Hz),135.4,134.9(q,J＝43.4Hz),132.1,129.3(q,J＝1.4Hz),129.1,127.2,125.5,123.8,119.4(q,J＝268.4Hz)；¹⁹F NMR(CDCl₃,376MHz):δ-60.2；HRMS(MALDI):335.0636(C₁₆H₉F₃N₂O₃,[M+H]⁺).

Example 6 preparation of 4- (4-cyanophenyl) -2-phenyl-5- (trifluoromethyl) oxazole (Compound 6)

The preparation method is the same as example 1. 1- (4-cyanophenyl) -2-diazo-3, 3, 3-trifluoropropane-1-ketone is used for replacing 2-diazo-3, 3, 3-trifluoro-1-phenylpropane-1-ketone, and a white solid target compound is obtained. The yield was 71%. And Mp: 119 ℃ and 125 ℃.¹H NMR(CDCl₃,400MHz):δ8.17-8.12(m,2H),7.91(d,J＝8.4Hz,2H),7.81-7.74(m,2H),7.60-7.50(m,3H)；¹³C{¹H}NMR(CDCl₃,100MHz):δ162.1,140.5(q,J＝2.4Hz),134.6(q,J＝37.8Hz),133.6,132.4,132.0,129.1,127.2,125.5,119.4(q,J＝268.5Hz),118.3,113.2；¹⁹F NMR(CDCl₃,376MHz):δ-60.2；HRMS(MALDI):315.0742(C₁₇H₉F₃N₂O,[M+H]⁺).

Example 7 preparation of 2-phenyl-5- (trifluoromethyl) -4- (4- (trifluoromethyl) phenyl) oxazole (Compound 7)

The preparation method is the same as example 1. 1- (4-trifluoromethylphenyl) -2-diazo-3, 3, 3-trifluoropropane-1-ketone is used for replacing 2-diazo-3, 3, 3-trifluoro-1-phenylpropane-1-ketone, and a white solid target compound is obtained. The yield was 98%. And Mp: 112 ℃ and 115 ℃.¹H NMR(CDCl₃,400MHz):δ8.18-8.13(m,2H),7.91(d,J＝8.2Hz,2H),7.75(d,J＝8.2Hz,2H),7.59-7.50(m,3H)；¹³C{¹H}NMR(CDCl₃,100MHz):δ162.0,141.0(d,J＝2.0Hz),134.3(d,J＝43.2Hz),132.8,131.9,131.5(d,J＝33.1Hz),129.0,128.8,127.2,125.7,125.6(d,J＝3.7Hz),123.9(q,J＝272.0Hz),119.6(q,J＝268.7Hz)；¹⁹F NMR(CDCl₃,376MHz):δ-60.2,-62.8；HRMS(MALDI):358.0662(C₁₇H₉F₆NO,[M+H]⁺).

EXAMPLE 8 preparation of 4- (Naphthalen-1-yl) -2-phenyl-5- (trifluoromethyl) oxazole (Compound 8)

The preparation method is the same as example 1. 1- (1-naphthyl) -2-diazo-3, 3, 3-trifluoropropane-1-ketone is used for replacing 2-diazo-3, 3, 3-trifluoro-1-phenylpropane-1-ketone to obtain a white solid target compound. The yield was 97%. And Mp: 80-82 ℃.¹H NMR(CDCl₃,400MHz):δ8.23-8.18(m,2H),7.99(d,J＝7.4Hz,2H),7.96-7.91(m,1H),7.60(d,J＝6.5Hz,1H),7.58-7.51(m,6H)；¹³C{¹H}NMR(CDCl₃,100MHz):δ162.1,141.8(q,J＝2.3Hz),135.7(q,J＝42.2Hz),133.7,131.8,131.6,130.2,129.0,128.5,128.4,127.2,126.8,126.6,126.3,126.0,125.3,124.9,119.5(q,J＝268.3Hz)；¹⁹F NMR(CDCl₃,376MHz):δ-60.9；HRMS(MALDI):340.0943(C₂₀H₁₂F₃NO,[M+H]⁺).

EXAMPLE 9 preparation of 4- (benzo [ d ] [1,3] dioxin-5-yl) -2-phenyl-5- (trifluoromethyl) oxazole (Compound 9)

The preparation method is the same as example 1. With 1- (benzo [ d ]][1,3]Dioxin-5-yl) -2-diazo-3, 3, 3-trifluoropropane-1-ketone replaces 2-diazo-3, 3, 3-trifluoro-1-phenylpropane-1-ketone to obtain a white solid target compound. The yield was 90%. And Mp: 80-82 ℃.¹H NMR(CDCl₃,400MHz):δ8.13(dd,J＝7.8,1.7Hz,2H),7.57-7.44(m,3H),7.30(dd,J＝8.1,1.6Hz,1H),7.27-7.25(m,1H),6.90(d,J＝8.1Hz,1H),6.02(s,2H)；¹³C{¹H}NMR(CDCl₃,100MHz):δ161.4,148.8,147.9,142.1(q,J＝2.3Hz),132.8(q,J＝42.7Hz),131.6,128.9,127.1,126.0,123.1,122.8(q,J＝1.6Hz),119.9(q,J＝267.8Hz),108.8,108.5,101.4；HRMS(MALDI):390.0685(C₁₇H₁₀F₃NO₃,[M+H]⁺).

EXAMPLE 10 preparation of 4- (3, 5-dimethylphenyl) -2-phenyl-5- (trifluoromethyl) oxazole (Compound 10)

The preparation method is the same as example 1. 2-diazo-1- (3, 5-dimethylphenyl) -3,3, 3-trifluoropropane-1-ketone is used for replacing 2-diazo-3, 3, 3-trifluoro-1-phenylpropane-1-ketone, and a white solid target compound is obtained. The yield was 88%. And Mp: 71-73 ℃.¹H NMR(CDCl₃,400MHz):δ8.22-8.11(m,2H),7.58-7.47(m,3H),7.40(s,2H),7.10(s,1H),2.41(s,3H),2.40(s,3H)；¹³C{¹H}NMR(CDCl₃,100MHz):δ161.5,142.7(q,J＝2.5Hz),138.2,133.3(q,J＝42.5Hz),131.5,131.3,129.1,128.9,127.1,126.2(q,J＝1.5Hz),126.1,119.8(q,J＝268.0Hz),21.3；¹⁹F NMR(CDCl₃,376MHz):δ-60.0；HRMS(MALDI):318.1098(C₁₈H₁₄F₃NO,[M+H]⁺).

Example 11 preparation of 4-heptadecyl-2-phenyl-5- (trifluoromethyl) oxazole (Compound 11)

The preparation method is the same as example 1. Replacing 2-diazo-3, 3, 3-trifluoro-1-phenylpropane-1-ketone with 2-diazo-1, 1, 1-trifluoro eicosane-3-ketone to obtain the colorless oily target compound. The yield was 62%.¹H NMR(CDCl₃,400MHz):δ8.07(dd,J＝7.8,1.7Hz,2H),7.52–7.45(m,3H),2.74–2.64(m,2H),1.71(dt,J＝15.1,6.8Hz,3H),1.25(s,27H),0.88(t,J＝6.8Hz,3H)；¹³C{¹H}NMR(CDCl₃,100MHz):δ161.9,144.0(q,J＝2.1Hz),134.0(q,J＝41.8Hz),131.4,128.9,127.0,126.3,120.0(q,J＝267.1Hz),31.9,29.69,29.65,29.61,29.5,29.4,29.3,29.1,28.7,26.1,22.7,14.1；¹⁹F NMR(CDCl₃,376MHz):δ-61.3；HRMS(MALDI):452.3136(C₂₇H₄₀F₃NO,[M+H]⁺)。

Example 12 preparation of 4- ((3r, 5r, 7r) -adamantan-1-yl) -2-phenyl-5- (trifluoromethyl) oxazole (Compound 12)

The preparation method is the same as example 1. 1-adamantyl-2-diazo-3, 3, 3-trifluoropropane-1-ketone is used for replacing 2-diazo-3, 3, 3-trifluoro-1-phenylpropane-1-ketone, and a white solid target compound is obtained. The yield was 55%. And Mp: 71-75 ℃.¹H NMR(CDCl₃,400MHz):δ8.10-8.02(m,2H),7.52-7.43(m,3H),2.09(s,2H),2.07(s,6H),1.79(d,J＝2.6Hz,6H)；¹³C{¹H}NMR(CDCl₃,100MHz):δ159.9,151.7(q,J＝2.4Hz),133.5(q,J＝42.7Hz),131.1,128.8,126.9,126.5,120.1(q,J＝267.7Hz),40.9,36.6,28.4；¹⁹F NMR(CDCl₃,376MHz):δ-56.0；HRMS(MALDI):348.1569(C₂₀H₂₀F₃NO,[M+H]⁺)。

EXAMPLE 13 preparation of 5- (Perfluoroethyl) -2, 4-Diphenyloxazole (Compound 13)

The preparation method is the same as example 1. Replacing 2-diazo-3, 3, 3-trifluoro-1-phenylpropane-1-ketone with 2-diazo-3, 3,4, 4-pentafluoro-1-phenylbutan-1-one to obtain the target compound of colorless oil. The yield was 87%.¹H NMR(CDCl₃,400MHz):δ8.21-8.11(m,2H),7.81-7.72(m,2H),7.64-7.40(m,6H)；¹³C{¹H}NMR(CDCl₃,100MHz):δ162.6,145.1,132.2(t,J＝34.5Hz),131.7,129.6,129.5,129.0,128.8(t,J＝2.6Hz),128.5,127.1,126.0,118.7(qt,J＝286.8,37.9Hz),109.8(tq,J＝252.9,40.5Hz)；¹⁹F NMR(CDCl₃,376MHz):δ-83.6,-111.5；HRMS(MALDI):340.0756(C₁₇H₁₀F₅NO,[M+H]⁺)。

EXAMPLE 14 preparation of 5- (perfluorobutyl) -2, 4-diphenyloxazole (Compound 14)

The preparation method is the same as example 1. 2-diazo-5, 5,5,5,5, 5-heptafluoro-1-phenylpentane-1-one is used for replacing 2-diazo-3, 3, 3-trifluoro-1-phenylpropane-1-one to obtain a white solid target compound, wherein the yield is 84%. And Mp: 45-49 ℃.¹H NMR(CDCl₃,400MHz):δ8.16(dd,J＝7.8,1.6Hz,1H),7.81-7.70(m,1H),7.59-7.44(m,3H)；¹³C{¹H}NMR(CDCl₃,100MHz):δ162.79,145.43,132.16(t,J＝34.4Hz),131.74,129.61,128.97,128.85,128.43,127.14,125.94,119.55-105.62(m)；¹⁹F NMR(CDCl₃,376MHz):δ-80.3,-109.2,126.1；HRMS(MALDI):390.0722(C₁₈H₁₀F₇NO,[M+H]⁺)。

Example 15 preparation of 2- (4-bromophenyl) -4-phenyl-5- (trifluoromethyl) oxazole (Compound 15)

The preparation method is the same as example 1. 4-bromobenzamide is used instead of benzamide to obtain the target compound as a white powder. The yield was 98%. Compound 15 is a known compound, and the nuclear magnetic hydrogen spectrum, nuclear magnetic carbon spectrum, nuclear magnetic fluorine spectrum, high-resolution mass spectrum and melting point are shown in Tsai, Y. -L.; fan, y. -s.; lee, c. -j.; huang, C. -H.; das, u.; lin, w.chem.Commun.2013,49, 10266-10268.

Example 16 preparation of 2- (4-bromophenyl) -4-phenyl-5- (trifluoromethyl) oxazole (Compound 16)

The preparation method is the same as example 1. The benzamide was replaced by 2-bromobenzamide to give the title compound as a white powder. The yield was 93%. Compound 16 is a known compound, and the nuclear magnetic hydrogen spectrum, nuclear magnetic carbon spectrum, nuclear magnetic fluorine spectrum, high resolution mass spectrum and melting point are shown in Tsai, Y. -L.; fan, y. -s.; lee, c. -j.; huang, C. -H.; das, u.; lin, w.chem.Commun.2013,49, 10266-10268.

Example 17 preparation of 2- (4-methoxyphenyl) -4-phenyl-5- (trifluoromethyl) oxazole (Compound 17)

The preparation method is the same as example 1. 4-methoxybenzamide is used for replacing benzamide to obtain the target compound as a white solid. The yield was 92%. Compound 17 is a known compound, and the nuclear magnetic hydrogen spectrum, nuclear magnetic carbon spectrum, nuclear magnetic fluorine spectrum, high-resolution mass spectrum and melting point are shown in Tsai, Y. -L.; fan, y. -s.; lee, c. -j.; huang, C. -H.; das, u.; lin, w.chem.Commun.2013,49, 10266-10268.

Example 18 preparation of 4-phenyl-5- (trifluoromethyl) -2- (4-vinylphenyl) oxazole (Compound 18)

The preparation method is the same as example 1. 4-vinyl benzamide is used instead of benzamide to obtain the target compound as colorless oil. The yield was 88%.¹H NMR(CDCl₃,400MHz):δ8.11(d,J＝8.4Hz,2H),7.83-7.73(m,2H),7.58-7.42(m,5H),6.77(dd,J＝17.6,10.9Hz,1H),5.89(d,J＝17.6Hz,1H),5.40(d,J＝10.9Hz,1H)；¹³C{¹H}NMR(CDCl₃,100MHz):δ161.5,142.5(q,J＝2.2Hz),140.7,135.9,133.4(q,J＝43.0Hz),129.6,129.3,12868,128.5(q,J＝1.9Hz),127.3,126.7,125.1,119.8(q,J＝268.3Hz),116.2；¹⁹F NMR(CDCl₃,376MHz):δ-60.1；HRMS(MALDI):316.0942(C₁₈H₁₂F₃NO,[M+H]⁺)。

EXAMPLE 19 preparation of 2- (benzofuran-6-yl) -4-phenyl-5- (trifluoromethyl) oxazole (Compound 19)

The preparation method is the same as example 1. Benzofuran-6-carboxamide was used instead of benzamide to give the title compound as a colorless oil. The yield was 94%.¹H NMR(CDCl₃,400MHz):δ8.30(s,1H),8.07(d,J＝8.1Hz,1H),7.81(d,J＝6.8Hz,2H),7.76(d,J＝2.1Hz,1H),7.71(d,J＝8.2Hz,1H),7.53-7.45(m,3H),6.84(d,J＝1.2Hz,1H)；¹³C{¹H}NMR(CDCl₃,100MHz):δ162.0,154.7,147.5,142.5(q,J＝2.2Hz),133.4(q,J＝42.6Hz),130.6,129.6,129.4,128.6,128.5,122.2,121.9,121.7,119.8(q,J＝267.9Hz),110.5,106.9；¹⁹F NMR(CDCl₃,376MHz):δ-60.0；HRMS(MALDI):330.0736(C₁₈H₁₀F₃NO₂,[M+H]⁺)。

EXAMPLE 20 preparation of 2- (benzofuran-2-yl) -4-phenyl-5- (trifluoromethyl) oxazole (Compound 20)

The preparation method is the same as example 1. Benzofuran-2-carboxamide is used instead of benzamide to obtain the target compound as a white solid. The yield was 83%. And Mp: 84-86 ℃.¹H NMR(CDCl₃,400MHz):δ7.82-7.77(m,2H),7.71(d,J＝7.4Hz,1H),7.65(dd,J＝8.4,0.8Hz,1H),7.58(d,J＝0.8Hz,1H),7.52-7.43(m,4H),7.36-7.31(m,1H)；¹³C{¹H}NMR(CDCl₃,100MHz):δ155.7,154.3,142.8(q,J＝2.6Hz),142.4,133.7(q,J＝43.2Hz),129.9,128.61,128.56(q,J＝1.8Hz),127.3,127.1,124.0,122.3,119.5(q,J＝268.2Hz),112.1,110.2；¹⁹F NMR(CDCl₃,376MHz):δ-60.1；HRMS(MALDI):330.0739(C₁₈H₁₀F₃NO₂，[M+H]⁺)。

Example 21 preparation of (8S, 9R, 13R, 14R) -13-methyl-3- (4-phenyl-5- (trifluoromethyl) oxazol-2-yl) -6,7,8,9,11,12,13,14,15, 16-decahydro-17H-cyclopenta [ a ] phenanthren-17-one (Compound 21)

The preparation method is the same as example 1. To prepare (8S, 9R, 13R, 14R) -13-methyl-17-oxo-7, 8,9,11,12,13,14,15,16, 17-decahydro-6H-cyclopentane [ a ]]Phenanthrene-3-formamide replaces benzamide to obtain the target compound as a white solid. The yield was 91%. And Mp: 123 ℃ and 128 ℃.¹H NMR(CDCl₃,400MHz):δ7.89(d,J＝10.9Hz,2H),7.79-7.74(m,2H),7.51-7.39(m,4H),3.06-2.92(m,2H),2.60-2.43(m,2H),2.41-2.30(m,1H),2.20-1.98(m,4H),1.68-1.48(m,6H),0.94(s,3H)；¹³C{¹H}NMR(CDCl₃,100MHz):δ220.6,161.9,143.9,142.4(q,J＝2.3Hz),137.4,133.2(q,J＝42.6Hz),129.5,129.4,128.6,128.5,127.6,126.0,124.4,123.4,119.8(q,J＝267.9Hz),50.5,47.9,44.6,37.8,35.8,31.5,29.2,26.2,25.6,21.6,13.8；¹⁹F NMR(CDCl₃,376MHz):δ-60.1；HRMS(MALDI):466.1982(C₂₈H₂₆F₃NO₂，[M+H]⁺)。

EXAMPLE 22 preparation of (E) -4-phenyl-2-styryl-5- (trifluoromethyl) oxazole (Compound 22)

The preparation method is the same as example 1. The cinnamide is used for replacing benzamide to obtain the target compound in colorless oily state. The yield was 88%.¹H NMR(CDCl₃,400MHz):δ7.77-7.68(m,3H),7.61-7.56(m,2H),7.49-7.39(m,6H),6.99(d,J＝16.4Hz,1H)；¹³C{¹H}NMR(CDCl₃,100MHz):δ161.4,142.5(q,J＝2.4Hz),139.4,134.8,133.0(q,J＝42.7Hz),129.9,129.6,129.2,129.0,128.6,128.4,127.5,119.7(q,J＝267.6Hz),112.4；¹⁹F NMR(CDCl₃,376MHz):δ-60.1；HRMS(MALDI):316.0942(C₁₈H₁₂F₃NO,[M+H]⁺)。

Example 23 preparation of 2-benzyl-4-phenyl-5- (trifluoromethyl) oxazole (Compound 23)

The preparation method is the same as example 1. The benzamide was replaced with phenylacetamide to give the objective compound as a colorless oil. The yield was 56%. δ 7.73-7.64(m,2H),7.47-7.40(m,3H),7.40-7.33(m,4H),7.33-7.27(m,1H),4.20(s, 2H);¹³C{¹H}NMR(CDCl₃,100MHz):δ163.5,141.5,134.2,129.5,129.2,128.9,128.5,128.4,127.4,119.6(q,J＝268.0Hz),34.5；¹⁹F NMR(CDCl₃,376MHz):δ-60.3；HRMS(MALDI):304.0947(C₁₇H₁₂F₃NO,[M+H]⁺)。