A process for the preparation of a trans-4,5-disubstituted oxazolidinone compound

Abstract

The application discloses a preparation method of a trans-4,5-di-substituted oxazolidinone compound, a [4+1] cyclization reaction of an aldimine and an oxysulfur ylide catalyzed by an iron salt, a product configuration is trans, and the product has high diastereoselectivity (d.r.>20:1). The application provides a new synthesis route of the trans-4,5-di-substituted oxazolidinone compound, which has the advantages of high efficiency, relatively mild reaction conditions, cheap and easily obtained raw materials, wide substrate application range, excellent functional group tolerance, high atom and step economy and the like, and has a potential application prospect in the field of drug synthesis.

Description

Technical Field

[0001] This invention belongs to the field of organic compound synthesis technology, specifically relating to a method for preparing trans-4,5-disubstituted oxazolidinone compounds. Background Technology

[0002] Oxazolidinones are an important class of organic synthetic intermediates and drug molecular skeletons, widely used in pharmaceuticals, pesticides, and fine chemicals. For example, oxazolidinone antibiotics are a new class of antibacterial drugs developed after sulfonamides and quinolones, possessing the ability to inhibit multidrug-resistant Gram-positive bacteria, such as linezolid, epperazolamide, and radizolide. Furthermore, muscle relaxants and anxiolytics like mefenoxuron, migraine treatments like zolmitriptan, treatments for spinocerebellar degeneration like lovatoprene, and cholesterol-lowering drugs like acetrapeptide all contain the core skeleton of oxazolidinones. Therefore, in the past few decades, exploring inexpensive, green, and efficient methods for synthesizing oxazolidinones has attracted great attention from organic and medicinal chemists.

[0003]

[0004] The current methods for constructing oxazolidinone skeletons include: (1) cyclization reaction of β-amino alcohols with carbonyl compounds (Chin. J. Chem. 2005, 23, 643-645); (2) cyclization reaction of ethylene oxide with isocyanates (Org. Lett. 2017, 19, 5786-5789); (3) iron-catalyzed ammoniation-hydroxyl bifunctionalization reaction of urethanes in intramolecular or intermolecular alkenes (J. Am. Chem. Soc. 2013, 135, 3343-3346; J. Am. Chem. Soc. 2014, 136, 13186-13189); (4) transition metal catalysis of intramolecular C(sp) groups in urethane molecules. 3 (5) [4+1] cyclization of organocatalysts with nitroolefins by sulfur ylide (J.Am.Chem.Soc.2008,130,6946-6948); (6) Amination-hydroxylation of α,β-unsaturated ketones (Chem.Commun.2012,48,6112-6114).

[0005] The methods described above for constructing oxazolidinone skeletons have several drawbacks, such as cumbersome raw material preparation steps, high reagent toxicity, harsh reaction conditions, low functional group tolerance, and narrow substrate universality. Therefore, developing a highly efficient method for preparing 4,5-disubstituted oxazolidinone compounds that uses inexpensive and readily available low-toxicity raw materials, has a wide range of applicable substrates, and exhibits high stereoselectivity is of great significance in the field of organic synthesis. Summary of the Invention

[0006] The purpose of this section is to outline some aspects of embodiments of the present invention and to briefly describe some preferred embodiments. Simplifications or omissions may be made in this section, as well as in the abstract and title of this application, to avoid obscuring the purpose of these documents; however, such simplifications or omissions should not be construed as limiting the scope of the invention.

[0007] In view of the problems existing in the above and / or prior art, the present invention is proposed.

[0008] One objective of this invention is to provide a method for preparing trans-4,5-disubstituted oxazolidinone compounds. The new synthetic route has the advantages of milder reaction conditions, better functional group tolerance, a wide range of applicable substrates, and high diastereoselectivity of the product.

[0009] To solve the above-mentioned technical problems, the present invention provides the following technical solution: a method for preparing a trans-4,5-disubstituted oxazolidinone compound, comprising,

[0010] The aldimine shown in Formula I and the oxysulfide shown in Formula II undergo a diastereoselective [4+1] cyclization reaction in the presence of a Lewis acid catalyst to give the compound shown in Formula III.

[0011]

[0012] In the formula, R 1 and R 2 The same or different are selected from one of phenyl or substituted phenyl, naphthyl, heteroaryl, alkyl or cycloalkyl;

[0013] R 3 It is one of isopropyl, benzyl, and tert-butyl;

[0014] In a preferred embodiment of the method for preparing the disubstituted oxazolidinone compound of the present invention, the aldehyde imine is N-tert-butoxycarbonylbenzaldehyde imine, N-tert-butoxycarbonyl-p-toluene formaldehyde imine, N-tert-butoxycarbonyl-p-fluorobenzaldehyde imine, N-tert-butoxycarbonyl-o-toluene formaldehyde imine, N-tert-butoxycarbonyl-p-tert-butylbenzaldehyde imine, N-tert-butoxycarbonyl-p-bromobenzaldehyde imine, N-tert-butoxycarbonyl-p-trifluoromethylbenzaldehyde imine, N-tert-butoxycarbonyl-p-nitrobenzaldehyde imine, or N-tert-butoxycarbonyl-p-methoxycarbonyl One of the following: N-tert-butoxycarbonyl-p-cyanobenzaldehyde imine, N-tert-butoxycarbonyl-p-pinacolborate-benzaldehyde imine, N-tert-butoxycarbonyl-o-fluorobenzaldehyde imine, N-tert-butoxycarbonyl-m-nitrobenzaldehyde imine, N-tert-butoxycarbonyl-m-toluenebenzaldehyde imine, N-tert-butoxycarbonyl-(3-methoxy-4-chloro)benzaldehyde imine, N-tert-butoxycarbonyl-(2-nitro-5-bromo)benzaldehyde imine, N-tert-butoxycarbonyl-2-naphthylcarboxaldehyde imine, and N-tert-butoxycarbonylcyclohexylcarboxaldehyde imine.

[0015] In a preferred embodiment of the method for preparing the disubstituted oxazolidinone compound of the present invention, the oxosulfur ylide is: benzoyl oxosulfur ylide, p-toluyl oxosulfur ylide, p-methoxybenzoyl oxosulfur ylide, p-bromobenzoyl oxosulfur ylide, 1,3-methylenedioxybenzoyl oxosulfur ylide, p-chlorobenzoyl oxosulfur ylide, p-trifluoromethylbenzoyl oxosulfur ylide, o-methoxybenzoyl oxosulfur ylide. One of the following: thioyl ylide, m-methoxybenzoyloxythioyl ylide, m-fluorobenzoyloxythioyl ylide, m-tolyloxythioyl ylide, 3-methyl-4-fluorobenzoyloxythioyl ylide, 2-naphthoyloxythioyl ylide, 2-furanoyloxythioyl ylide, 2-thiophenecarboxyyloxythioyl ylide, 2-benzothiophenecarboxyyloxythioyl ylide, phenylacetyloxythioyl ylide, and p-methoxyphenylpropionyloxythioyl ylide.

[0016] In a preferred embodiment of the method for preparing the disubstituted oxazolidinone compound of the present invention, the Lewis acid is one of the following: silver bis(trifluoromethanesulfonyl)imide, zinc trifluoromethanesulfonate, copper trifluoromethanesulfonate, scandium trifluoromethanesulfonate, zinc acetate, zinc chloride, silver hexafluoroantimonate, ferric chloride, indium trifluoromethanesulfonate, tin tetrachloride, ferrous trifluoromethanesulfonate, ferric trifluoromethanesulfonate, and silver trifluoromethanesulfonate, more preferably ferrous trifluoromethanesulfonate.

[0017] In a preferred embodiment of the method for preparing the disubstituted oxazolidinone compound of the present invention, the solvent is one of trifluorotoluene, 1,2-dichloroethane, dichloromethane, tetrahydrofuran, toluene, methyl tert-butyl ether, dimethyl sulfoxide, and methanol, more preferably dichloromethane.

[0018] In a preferred embodiment of the method for preparing the disubstituted oxazolidinone compound of the present invention, the molar volume ratio of the aldimine, oxysulfide, Lewis acid and solvent is 0.15 mmol: 0.18–0.225 mmol: 0.0075–0.015 mmol: 1.5 mL.

[0019] In a preferred embodiment of the method for preparing the disubstituted oxazolidinone compound of the present invention, the reaction temperature is 40–100 °C and the reaction time is 12 h.

[0020] In a preferred embodiment of the method for preparing the disubstituted oxazolidinone compound of the present invention, the solvent is dichloromethane and the reaction temperature is 60-70°C.

[0021] In a preferred embodiment of the method for preparing the disubstituted oxazolidinone compound of the present invention, the solvent is chlorobenzene and the reaction temperature is 70-80°C.

[0022] In a preferred embodiment of the method for preparing the disubstituted oxazolidinone compound of the present invention, the solvent is one of trifluorotoluene, 1,2-dichloroethane, dichloromethane, and tetrahydrofuran, and the reaction temperature is 70°C.

[0023] As a preferred embodiment of the method for preparing the disubstituted oxazolidinone compound of the present invention, the method further includes a step of purifying the target product.

[0024] In summary, the chemical reaction formula of this invention is:

[0025]

[0026] Compared with the prior art, the present invention has the following beneficial effects:

[0027] The Lewis acids and starting materials used in this invention, including aldimines and oxythiol ylides, are relatively inexpensive, readily available, and highly stable. Compared with traditional polysubstituted oxazolidinone synthesis routes, this method is more green and efficient, has simpler steps, a wider range of applicable substrates, excellent functional group tolerance, and specific stereoselectivity of the product. Attached Figure Description

[0028] To more clearly illustrate the technical solutions of the embodiments of the present invention, the drawings used in the description of the embodiments will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present invention. For those skilled in the art, other drawings can be obtained based on these drawings without creative effort. Wherein:

[0029] Figure 1 The hydrogen nuclear magnetic resonance spectrum of the target product in Example 1 of this invention;

[0030] Figure 2 The nuclear magnetic resonance carbon spectrum of the target product in Example 1 of this invention;

[0031] Figure 3 The hydrogen nuclear magnetic resonance spectrum of the target product in Example 4 of this invention;

[0032] Figure 4 This is the carbon NMR spectrum of the target product in Example 4 of the present invention. Detailed Implementation

[0033] To make the above-mentioned objects, features and advantages of the present invention more apparent and understandable, the specific embodiments of the present invention will be described in detail below with reference to the examples in the specification.

[0034] Many specific details are set forth in the following description in order to provide a full understanding of the invention. However, the invention may also be practiced in other ways different from those described herein, and those skilled in the art can make similar extensions without departing from the spirit of the invention. Therefore, the invention is not limited to the specific embodiments disclosed below.

[0035] Secondly, the term "one embodiment" or "embodiment" as used herein refers to a specific feature, structure, or characteristic that may be included in at least one implementation of the present invention. The phrase "in one embodiment" appearing in different places in this specification does not necessarily refer to the same embodiment, nor is it a single or selective embodiment that is mutually exclusive with other embodiments.

[0036] Unless otherwise specified, the raw materials used in the examples, including Lewis acids and solvents, were commercially available. Aldehydeimide (J. Am. Chem. Soc., 2002, 124, 12964-12965) and oxysulfide (Org. Lett., 2020, 22, 1375-1379) were prepared according to methods described in existing literature.

[0037] Example 1

[0038] N-tert-butyloxycarbonylbenzaldehyde imine (0.225 mmol, 46.2 mg), benzoyloxythioyl ylide (0.15 mmol, 29.4 mg), ferrous trifluoromethanesulfonate (0.015 mmol, 5.3 mg), and 1.5 mL of dichloromethane were added to a 4 mL screw-capped reaction flask. Nitrogen gas was purged into the flask for 30 s, and the mixture was heated to 60 °C and stirred for 12 h. After the reaction was completed, the reaction solution was cooled to room temperature. No post-treatment was required, and the solid was separated by silica gel column chromatography to obtain a white solid (31.7 mg). The yield was 79% (dr > 20:1), and the purity was > 98%.

[0039] The structural formula of this compound is:

[0040]

[0041] The proton NMR spectrum of the target product is shown below. Figure 1 As shown, the carbon NMR spectrum is as follows: Figure 2 As shown; the characterization data is as follows: 1 H NMR (400MHz, CDCl3) δ7.95 (dd, J=8.5, 1.3Hz, 2H), 7.68–7.58 (m, 1H), 7.48 (t, J=7.8Hz, 2H),7.44–7.35(m,5H),6.07(s,1H),5.47(d,J=5.7Hz,1H),5.34(dd,J=5.6,1.1Hz,1H). 13 C NMR (101MHz, CDCl3) δ192.3,157.6,139.0,134.5,133.7,129.4×2,129.3×2,129.0,128.8×2,126.3×2,83.3,57.1.HRMS(ESI):m / zcalculated for C 16 H 14 NO3[M+H] + :268.0986,found:268.0973.

[0042] Characterization data indicate that the obtained product is trans-4-phenyl-5-benzoyl-2-oxazolidinone.

[0043] The product trans-4-phenyl-5-benzoyl-2-oxazolidinone synthesized in this embodiment can be used as an intermediate in the synthesis of the drug molecule docetaxel. Docetaxel is obtained by introducing a side chain at the C13 position of the precursor 10-deacetylbaccatin III (abbreviated as 10-DBAI11) isolated from yew, and is a semi-synthetic taxane antitumor drug.

[0044] Example 2

[0045] N-tert-butyloxycarbonyl-p-tolueneformaldehyde imine (0.225 mmol, 49.3 mg), benzoyloxythioyl ylide (0.15 mmol, 29.4 mg), ferrous trifluoromethanesulfonate (0.015 mmol, 5.3 mg), and 1.5 mL of dichloromethane were added to a 4 mL screw-capped reaction flask. Nitrogen gas was purged into the flask for 30 s, and the mixture was heated to 60 °C and stirred for 12 h. After the reaction was completed, the reaction solution was cooled to room temperature. No post-treatment was required, and the solid was separated by silica gel column chromatography to obtain a white solid (33.3 mg). The yield was 79% (dr > 20:1), and the purity was > 98%.

[0046] The structural formula of this compound is:

[0047]

[0048] The characterization data of the target product are as follows: 1 H NMR (400MHz, CDCl3) δ7.98–7.89(m,2H),7.66–7.58(m,1H),7.47(t,J=7.8Hz,2H),7.28(d,J=8.2Hz,2H ),7.21(d,J=7.8Hz,2H),6.29–6.04(m,1H),5.45(d,J=5.6Hz,1H),5.25(d,J=5.6Hz,1H),2.36(s,3H). 13 C NMR (101MHz, CDCl3) δ192.3,157.6,139.0,136.0,134.4,133.6,129.9×2,129.3×2,128.8×2,126.3×2,83.4,57.0,21.1.HRMS(ESI):m / z calculated for C 17 H 16 NO3[M+H] + :282.1125,found:282.1130.

[0049] Characterization data indicate that the obtained product is trans-4-p-tolyl-5-benzoyl-2-oxazolidinone.

[0050] Example 3

[0051] N-tert-butyloxycarbonyl-p-cyanobenzaldehyde imine (0.225 mmol, 51.8 mg), benzoylthioylide (0.15 mmol, 29.4 mg), ferrous trifluoromethanesulfonate (0.015 mmol, 5.3 mg), and 1.5 mL of dichloromethane were added to a 4 mL screw-capped reaction flask. Nitrogen gas was purged into the flask for 30 s, and the mixture was heated to 80 °C and stirred for 12 h. After the reaction was completed, the reaction solution was cooled to room temperature. No post-treatment was required, and the solid was separated by silica gel column chromatography to obtain a white solid (31.5 mg). The yield was 76% (dr > 20:1), and the purity was > 98%.

[0052] The structural formula of this compound is:

[0053]

[0054] The characterization data of the target product are as follows: 1 H NMR(400MHz,DMSO-d6)δ8.61(s,1H),7.96–7.82(m,4H),7.68(dd,J=8.2,6.7Hz,1H), 7.53(ddd,J=8.0,6.0,1.7Hz,4H), 5.95(dd,J=4.5,1.5Hz,1H), 5.11(d,J=4.4Hz,1H). 13 C NMR(101MHz,DMSO-d6)δ194.2,157.9,146.2,134.9,134.1,133.4,129.6,129.5,128.2,119.1,111.7,81.3,56.8.HRMS(ESI):m / z calculated for C 17 H 13 N₂O₃[M+H] + :293.0921,found:293.0926.

[0055] Characterization data indicate that the obtained product is trans-4-p-cyanophenyl-5-benzoyl-2-oxazolidinone.

[0056] Example 4

[0057] N-tert-butyloxycarbonylbenzaldehyde imine (0.225 mmol, 46.2 mg), p-tolueneoxythioyl ylide (0.15 mmol, 31.5 mg), ferrous trifluoromethanesulfonate (0.015 mmol, 5.3 mg), and 1.5 mL of dichloromethane were added to a 4 mL screw-capped reaction flask. Nitrogen gas was purged into the flask for 30 s, and the mixture was heated to 60 °C and stirred for 12 h. After the reaction was completed, the reaction solution was cooled to room temperature. No post-treatment was required, and the solid was separated by silica gel column chromatography to obtain a white solid (36.8 mg). The yield was 87% (dr > 20:1), and the purity was > 98%.

[0058] The structural formula of this compound is:

[0059]

[0060] The proton NMR spectrum of the target product is shown below. Figure 3 As shown, the carbon NMR spectrum is as follows: Figure 4 As shown; the characterization data is as follows: 1 H NMR (400MHz, CDCl3) δ7.73–7.67(m,2H),7.31–7.21(m,5H),7.14(d,J=0.8Hz,1H),7.12(d, J=0.7Hz,1H),6.36(s,1H),5.31(d,J=5.7Hz,1H),5.16(dd,J=5.7,1.1Hz,1H),2.29(s,3H). 13 C NMR (101MHz, CDCl3) δ191.8,157.9,145.6,139.1,131.1,129.5×2,129.4×2,129.2×2,128.9,126.3×2,83.2,57.2,21.8.HRMS(ESI):m / z calculated forC 17 H 16 NO3[M+H] + :282.1125,found:282.1130.

[0061] Characterization data indicate that the obtained product is trans-4-phenyl-5-p-toluamide-2-oxazolidinone.

[0062] Example 5

[0063] N-tert-butyloxycarbonylbenzaldehyde imine (0.225 mmol, 46.2 mg), m-methoxybenzoyloxythioyl ylide (0.15 mmol, 33.9 mg), ferrous trifluoromethanesulfonate (0.015 mmol, 5.3 mg), and 1.5 mL of dichloromethane were added to a 4 mL screw-capped reaction flask. Nitrogen gas was purged into the flask for 30 s, and the mixture was heated to 100 °C and stirred for 12 h. After the reaction was completed, the reaction solution was cooled to room temperature. No post-treatment was required, and the solid was separated by silica gel column chromatography to obtain a white solid (34.8 mg). The yield was 78% (dr > 20:1), and the purity was > 98%.

[0064] The structural formula of this compound is:

[0065]

[0066] The characterization data of the target product are as follows: 1 H NMR (400MHz, CDCl3) δ7.51–7.46(m,2H),7.44–7.33(m,6H),7.16(ddd,J=8.3,2.5,1.1Hz,1 H), 6.00 (d, J = 12.9Hz, 1H), 5.47 (d, J = 5.7Hz, 1H), 5.28 (dd, J = 5.7, 1.1Hz, 1H), 3.83 (s, 3H). 13 C NMR (101MHz, CDCl3) δ192.0,159.9,138.9,134.8,129.9,129.3×2,129.1,126.4×2,122.0,121.3,113.0,83.2,57.2,55.4.HRMS(ESI):m / z calculated for C 17 H 16 NO4[M+H] + :298.1074,found:298.1079.

[0067] Characterization data indicate that the obtained product is trans-4-phenyl-5-m-methoxybenzoyl-2-oxazolidinone.

[0068] Example 6

[0069] N-tert-butyloxycarbonylbenzaldehyde imine (0.225 mmol, 46.2 mg), p-bromobenzoyloxythioylide (0.15 mmol, 41.2 mg), ferrous trifluoromethanesulfonate (0.015 mmol, 5.3 mg), and 1.5 mL of dichloromethane were added to a 4 mL screw-capped reaction flask. Nitrogen gas was purged into the flask for 30 s, and the mixture was heated to 60 °C and stirred for 12 h. After the reaction was completed, the reaction solution was cooled to room temperature. No post-treatment was required, and the solid was separated by silica gel column chromatography to obtain a white solid (40.5 mg). The yield was 78% (dr > 20:1), and the purity was > 98%.

[0070] The structural formula of this compound is:

[0071]

[0072] The characterization data of the target product are as follows: 1 H NMR (400MHz, CDCl3) δ7.81 (d, J = 8.7Hz, 2H), 7.61 (d, J = 8.5Hz, 2H), 7.47–7.33 (m, 5H), 6.52 (s, 1H), 5.38 (d, J = 5.7Hz, 1H), 5.33 (d, J = 5.8Hz, 1H). 13 C NMR (101MHz, CDCl3) δ191.5,157.6,138.8,132.4,132.2×2,130.8×2,129.9,129.3×2,129.0,126.3×2,83.3,57.0.HRMS(ESI):m / zcalculated for C 16 H 13 BrNO3[M+H] + :346.0073,found:346.0079.

[0073] Characterization data indicate that the obtained product is trans-4-phenyl-5-p-bromobenzoyl-2-oxazolidinone.

[0074] Example 7

[0075] N-tert-butyloxycarbonylbenzaldehyde imine (0.225 mmol, 46.2 mg), 1,3-methylenedioxybenzoyloxythioylide (0.15 mmol, 36.0 mg), ferrous trifluoromethanesulfonate (0.015 mmol, 5.3 mg), and 1.5 mL of dichloromethane were added to a 4 mL screw-capped reaction flask. Nitrogen gas was purged into the flask for 30 s, and the mixture was heated to 60 °C and stirred for 12 h. After the reaction was completed, the reaction solution was cooled to room temperature. No post-treatment was required, and the solid was separated by silica gel column chromatography to obtain a white solid (42.1 mg). The yield was 90% (dr > 20:1), and the purity was > 98%.

[0076] The structural formula of this compound is:

[0077]

[0078] The characterization data of the target product are as follows: 1 H NMR (400MHz, CDCl3) δ7.51 (dd, J=8.2, 1.7Hz, 1H), 7.43 (d, J=1.8Hz, 1H), 7.42–7.33 (m, 5H), 6.8 2(d,J=8.2Hz,1H),6.31(s,1H),6.05(s,2H),5.36(d,J=5.8Hz,1H),5.32(dd,J=5.8,1.1Hz,1H). 13 C NMR (101MHz, CDCl3) δ190.1,157.7,152.9,148.4,139.0,129.3×2,128.9,128.4,126.4,126.3×2,108.7,108.1,102.1,83.2,57.1.HRMS(ESI):m / z calculated for C 17 H 14 NO5[M+H] + :312.0866,found:312.0872.

[0079] Characterization data indicate that the obtained product is trans-4-phenyl-5-((1,3-methylenedioxy)-benzoyl)-2-oxazolidinone.

[0080] Example 8

[0081] Example 8 is basically the same as Example 1, except that chlorobenzene is used as the solvent, the reaction temperature is 80°C, and the catalyst is different, as shown in Table 1 below.

[0082] Table 1

[0083] catalyst Yield (%) Silver bis(trifluoromethanesulfonyl)imide 52 Zinc trifluoromethanesulfonate 58 Copper trifluoromethanesulfonate 51 Zinc acetate <5 Zinc chloride <5 Silver hexafluoroantimonate 38 Ferric chloride 31 Indium trifluoromethanesulfonate 70 Tin tetrachloride 28 Ferric trifluoromethanesulfonate 51 Ferrous trifluoromethanesulfonate 75 Silver trifluoromethanesulfonate 37

[0084] As can be seen from the data in Table 1, under the same solvent and reaction temperature conditions, the catalytic efficiency of various Lewis acids is different, among which ferrous trifluoromethanesulfonate has the best catalytic effect.

[0085] Example 9

[0086] Example 9 is basically the same as Example 1, except that the type of solvent and the reaction temperature are different, as shown in Table 2 below.

[0087] Table 2

[0088]

[0089]

[0090] As shown in Table 2, using chlorobenzene as the solvent, lowering the reaction temperature from 80℃ to 70℃ slightly increased the yield (75% → 77%), while further lowering the temperature to 60℃ significantly decreased the yield (75% → 53%). At the same reaction temperature (70℃), the type of solvent significantly affected the reaction efficiency. No reaction occurred in methanol, the target product yield was extremely low in dimethyl sulfoxide, and the yield was higher in chlorobenzene or dichloromethane. Considering that dichloromethane is cheaper, more readily available, less toxic, and easier to remove than chlorobenzene, dichloromethane was ultimately chosen as the solvent. Finally, lowering the reaction temperature to 60℃ increased the yield to 79%, while further lowering the reaction temperature significantly decreased the yield.

[0091] Example 10

[0092] Example 10 is basically the same as Example 1, except that the aldehyde imine and thioyl ylide are different, as shown in Table 3 below.

[0093] Table 3

[0094]

[0095]

[0096]

[0097]

[0098] This invention provides a method for preparing trans-4,5-disubstituted oxazolidinone compounds, which is obtained by an iron salt-catalyzed diastereoselective [4+1] cyclization reaction of an aldehyde imine with an oxysulfur ylide. This invention avoids the use of expensive metal catalysts, uses inexpensive and readily available raw materials, and produces products with high diastereoselectivity. This synthetic method has the advantages of being green and efficient, simple in steps, having a wide range of applicable substrates, excellent functional group tolerance, and generating less waste.

[0099] It should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention and are not intended to limit it. Although the present invention has been described in detail with reference to preferred embodiments, those skilled in the art should understand that modifications or equivalent substitutions can be made to the technical solutions of the present invention without departing from the spirit and scope of the technical solutions of the present invention, and all such modifications or substitutions should be covered within the scope of the claims of the present invention.

Claims

1. A method for preparing a trans-4,5-disubstituted oxazolidinone compound, characterized in that: include, The aldimine shown in Formula I and the oxysulfide shown in Formula II undergo a diastereoselective [4+1] cyclization reaction in the presence of a Lewis acid catalyst to give the compound shown in Formula III. In the formula, R 1 and R 2 The same or different are selected from one of phenyl or substituted phenyl, naphthyl, heteroaryl, alkyl or cycloalkyl; R 3 It is one of isopropyl, benzyl, and tert-butyl; The Lewis acid catalyst is one of the following: silver bis(trifluoromethanesulfonyl)imide, zinc trifluoromethanesulfonate, copper trifluoromethanesulfonate, scandium trifluoromethanesulfonate, silver hexafluoroantimonate, ferric chloride, indium trifluoromethanesulfonate, tin tetrachloride, ferrous trifluoromethanesulfonate, ferric trifluoromethanesulfonate, and silver trifluoromethanesulfonate. The cyclization reaction is carried out in an organic solvent, the solvent including one of trifluorotoluene, 1,2-dichloroethane, dichloromethane, tetrahydrofuran, toluene, and methyl tert-butyl ether; The reaction temperature is 40–100°C, and the reaction time is 12 hours.

2. The preparation method according to claim 1, characterized in that: The Lewis acid catalyst is ferrous trifluoromethanesulfonate.

3. The preparation method according to any one of claims 1 or 2, characterized in that: The molar volume ratio of the aldimine, oxysulfide, Lewis acid, and solvent is 0.15 mmol: 0.18–0.225 mmol: 0.0075–0.015 mmol: 1.5 mL.

4. The preparation method according to claim 3, characterized in that: The solvent is dichloromethane, and the reaction temperature is 60–70°C.

5. The preparation method according to claim 4, characterized in that: The solvent is chlorobenzene, and the reaction temperature is 70–80°C.

6. The preparation method according to claim 1, characterized in that: The solvent is one of trifluorotoluene, 1,2-dichloroethane, dichloromethane, and tetrahydrofuran, and the reaction temperature is 70°C.

7. The preparation method according to claim 1, characterized in that: It also includes the step of purifying the target product.

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