A method for synthesizing an alkyl carbamate compound

Abstract

The application discloses a synthesis method of a carbamic acid alkyl ester compound, which comprises the following steps: dispersing an alkynyl high-valence iodine compound, a palladium catalyst, an amine, formic acid and a base in a solvent, and then introducing carbon dioxide to perform a reaction, so as to obtain the carbamic acid alkyl ester compound. The synthesis method of the carbamic acid alkyl ester compound has the advantages of cheap and easily obtained raw materials, mild reaction conditions, simple operation, high economy of steps, wide applicable range of substrates, good region selectivity and good functional group tolerance, and is suitable for large-scale industrial application.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of organic synthesis, and particularly relates to a synthesis method of carbamic acid alkyl ester compounds. BACKGROUND

[0002] Carbamates are an important class of nitrogen and oxygen-containing compounds, which are widely present in biological and pharmaceutical active molecules (Bhutani, P.; Joshi, G.; Raja, N.; Bachhav, N.; Rajanna, P. K.; Bhutani, H.; Paul, A. T.; Kumar, R. J. Med. Chem. 2021, 64, 2339), and have a wide application in pharmaceutical engineering, agricultural field and polymer material synthesis (Pizova, H.; Havelkova, M.; Stepankova, S.; Bak, A.; Kauerova, T.; Kozik, V.; Oravec, M.; Imramovsky, A.; Kollar, P.; Bobal, P.; Jampilek, J. Molecules. 2017, 22, 1969; Bhatt, P.; Zhou, X.; Huang, Y.; Zhang, W.; Chen, S. J. Hazard. Mater. 2021, 411, 125026).

[0003] Alkenyl carbamates are an important class of carbamates with unique biological activities, for example: novel fatty amide hydrolase inhibitors (Gattinoni, S.; Simone, D. C.; Dallavalle, S. F; Fezza, F.; Nannei, R.; Amadio, D.; Minetti, P.; Quattrociocchi, G.; Caprioli, A.; Borsini, F.; Cabri, W.; Penco, S.; Merlini, L.; Maccarrone, M. ChemMedChem 2010, 5, 357), HIV-1 type reverse transcriptase inhibitor S-2720 (Kleim, J. P.; Bender, R.; Billhardt, U. M.; Meichsner, C; Riess, G.; Rosner, M.; Winkler, I.; Paessens, A. Antimicrob. Agents Chemother. 1993, 37, 1659) and antitumor inhibitor Antitumor agent-48 (Wu, Q. C; Zeng, J.; Dong, J. F. Med. Chem. Res. 2022, 31, 533) all contain alkenyl carbamate structural units.In addition, the amino acid ester can also be used as a multifunctional synthon for organic synthesis, for example: under ruthenium or rhodium catalysis, the amino acid ester can realize C-H functionalization reaction to obtain polysubstituted olefins (Gong, T.-J.; Su, W.; Liu, Z-J.; Cheng, W.-M.; Xiao, B.; Fu, Y. Org. Lett. 2014, 16, 330; Sharma, S.; Han, S.H.; Jo, H.; Han, S.; Mishra, N.K.; Choi, M.; Jeong, T.; Park, Kim, J.; I. S. Eur. J. Org. Chem. 2016, 3611); under transition metal catalysis, the amino acid ester can undergo various cross-coupling reactions, including Kumada coupling reaction, Buchwald-Hartwig amination reaction (BHA), Mizoroki-Heck reaction (MHR) and Suzuki-Miyaura coupling reaction (SMC) and the like (Cristina, A.; Rivera, P.; Still, R.; Frantz, D.E. Angew. Chem. Int. Ed. 2016, 55, 6689; Toupalas, G.; Morandi. B. Nat. Catal. 2022, 5, 324; Koyama, S.; Takahashi, F.; Yorimitsu, H. Synthesis, 2023, 55, 1744); through the guiding effect of the amide group, the functionalization reaction of the ortho C-H bond of the benzene ring of the amino acid ester can be realized (Voth, S.; Hollett, J.W.; McCubbin, J.A. J. Org. Chem. 2015, 80, 2545; Miah, M.A.J.; Sibi, M.P.; Chattopadhyay, S.; Familoni, O.B.; Snieckus, V. Eur. J. Org. Chem. 2018, 4, 440; Bracegirdle, S.; Anderson, E.A. Chem. Commun. 2010, 46, 3454).

[0004] Currently, carbamic acid alkyl esters are mainly synthesized from highly toxic phosgene or isocyanate as raw materials, which can easily cause environmental pollution and safety accidents (Adams, P.; Baron, F. A. Chem. Rev. 1965, 65, 567; Ozaki, S. Chem. Rev. 1972, 72, 457; Panella, L.; Feringa, B. L.; Vries, J. G.; Minnaard, A. J. Org. Lett. 2005, 7, 19). In recent years, the use of carbon dioxide, a cheap, readily available and safe non-toxic raw material, to replace phosgene to synthesize carbamic acid esters has attracted much attention. However, the existing methods for synthesizing carbamic acid alkyl esters using carbon dioxide generally have problems such as harsh reaction conditions, narrow substrate scope, poor regioselectivity, and cannot fully meet the requirements of practical applications (Vessally, E.; Mohammadi, R.; Hosseinian, A.; Edjlali, L.; Babazadeh, M. J. CO2 Util. 2018, 24, 361; Schilling, W.; Das, S. ChemSusChem 2020, 13, 6246; Guo, Y.; Wei, L.; Wen, Z.; Qi, C.; Jiang, H. Acta Phys.-Chim. Sin. 2024, 40, 2307004).

[0005] Therefore, it is of great significance to develop a method for synthesizing carbamic acid alkyl ester compounds, which has cheap and readily available raw materials, mild reaction conditions, simple operation, wide substrate scope, and good regioselectivity. SUMMARY

[0006] The purpose of the present application is to provide a method for synthesizing carbamic acid alkyl ester compounds.

[0007] The technical solution adopted by the present application is:

[0008] A method for synthesizing carbamic acid alkyl ester compounds comprises the following steps:

[0009] The alkynyl hypervalent iodine compound, palladium catalyst, amine, formic acid and base are dispersed in a solvent, and then carbon dioxide is introduced for reaction to obtain the carbamic acid alkyl ester compound; the structure of the alkynyl hypervalent iodine compound is: In the formula, R 1 is one of hydrogen, fluorine, chlorine, bromine, methyl, ethyl, methoxy, trifluoromethyl, cyano, -CHO, phenyl, The amine is one of thiomorpholine, tetrahydropyrrole, hexahydropyridine, morpholine, N-methyl piperazine, in which R 2 and R3 independently one of methyl, ethyl, n-propyl, n-butyl, cyclohexyl, benzyl.

[0010] Preferably, the R 1 one of methyl, chloro, phenyl.

[0011] Preferably, the amine is one of thiomorpholine, tetrahydropyrrole, N-methylpiperazine.

[0012] Preferably, the molar ratio of the alkynyl hypervalent iodine compound, amine, formic acid is 1:2-3:1.2-2.0.

[0013] Preferably, the molar ratio of the alkynyl hypervalent iodine compound, palladium catalyst is 1:0.025-0.05.

[0014] Preferably, the palladium catalyst is at least one of dichlorobis(triphenylphosphine)palladium, tetrakis(triphenylphosphine)palladium, bis(benzonitrile)palladium, palladium acetate.

[0015] Further preferably, the palladium catalyst is dichlorobis(triphenylphosphine)palladium.

[0016] Preferably, the molar ratio of the alkynyl hypervalent iodine compound, base is 1:2-3.

[0017] Preferably, the base is at least one of 1,8-diazabicyclo[5.4.0]undec-7-ene, 1,5-diazabicyclo[4.3.0]non-5-ene, triethylamine, triethylenediamine.

[0018] Further preferably, the base is 1,8-diazabicyclo[5.4.0]undec-7-ene.

[0019] Preferably, the solvent is at least one of N,N-dimethylformamide, N,N-dimethylacetamide, acetonitrile, dimethylsulfoxide, tetrahydrofuran.

[0020] Preferably, the reaction is carried out under the conditions of a carbon dioxide pressure of 0.8 atm-1.2 atm and a temperature of 50°C-70°C, and the reaction time is 1 h-3 h.

[0021] Preferably, after the reaction is completed, the reaction product is further purified by column chromatography.

[0022] Preferably, the eluent used in the column chromatography purification is a mixed solvent composed of petroleum ether and ethyl acetate in a volume ratio of 20-50:1.

[0023] The synthesis reaction of the alkenyl carbamate compound of the present application is as follows:

[0024]

[0025] The aminoalkyl carbamate compounds synthesized by the method of the present application have the advantages of cheap and readily available raw materials, mild reaction conditions, simple operation, high economic efficiency of steps, wide substrate applicability, good regioselectivity and functional group tolerance, and are suitable for large-scale industrial application.

[0026] Specifically:

[0027] 1) The present application uses formic acid as a hydrogen source, and uses a palladium catalyst to catalyze the coupling reaction of an alkynyl hypervalent iodine compound, an amine and CO2 to synthesize various aminoalkyl carbamate compounds, which has a wide application prospect due to its mild reaction conditions, economical and safe operation steps, and wide substrate applicability.

[0028] 2) The synthesis method of the aminoalkyl carbamate compounds of the present application is novel and efficient, has good tolerance to functional groups, and is suitable for actual industrial production and further derivatization. BRIEF DESCRIPTION OF DRAWINGS

[0029] Figure 1 H NMR spectrum of the aminoalkyl carbamate compound synthesized for Example 1. 1 H NMR spectrum of the aminoalkyl carbamate compound synthesized for Example 1.

[0030] Figure 2 C NMR spectrum of the aminoalkyl carbamate compound synthesized for Example 1. 13 C NMR spectrum of the aminoalkyl carbamate compound synthesized for Example 1.

[0031] Figure 3 H NMR spectrum of the aminoalkyl carbamate compound synthesized for Example 2. 1 H NMR spectrum of the aminoalkyl carbamate compound synthesized for Example 2.

[0032] Figure 4 C NMR spectrum of the aminoalkyl carbamate compound synthesized for Example 2. 13 C NMR spectrum of the aminoalkyl carbamate compound synthesized for Example 2.

[0033] Figure 5 H NMR spectrum of the aminoalkyl carbamate compound synthesized for Example 3. 1 H NMR spectrum of the aminoalkyl carbamate compound synthesized for Example 3.

[0034] Figure 6 C NMR spectrum of the aminoalkyl carbamate compound synthesized for Example 3. 13 C NMR spectrum of the aminoalkyl carbamate compound synthesized for Example 3.

[0035] Figure 7 H NMR spectrum of the aminoalkyl carbamate compound synthesized for Example 4. 1 H NMR spectrum of the aminoalkyl carbamate compound synthesized for Example 4.

[0036] Figure 8 C NMR spectrum of the aminoalkyl carbamate compound synthesized for Example 4.13 H NMR spectrum.

[0037] Figure 9 H NMR spectrum of the amino acid ester compound synthesized for Example 5 1 H NMR spectrum.

[0038] Figure 10 H NMR spectrum of the amino acid ester compound synthesized for Example 5 13 H NMR spectrum.

[0039] Figure 11 H NMR spectrum of the amino acid ester compound synthesized for Example 6 1 H NMR spectrum.

[0040] Figure 12 H NMR spectrum of the amino acid ester compound synthesized for Example 6 13 H NMR spectrum.

[0041] Figure 13 H NMR spectrum of the amino acid ester compound synthesized for Example 7 1 H NMR spectrum.

[0042] Figure 14 H NMR spectrum of the amino acid ester compound synthesized for Example 7 13 H NMR spectrum.

[0043] Figure 15 H NMR spectrum of the amino acid ester compound synthesized for Example 8 1 H NMR spectrum.

[0044] Figure 16 H NMR spectrum of the amino acid ester compound synthesized for Example 8 13 H NMR spectrum.

[0045] Figure 17 H NMR spectrum of the amino acid ester compound synthesized for Example 9 1 H NMR spectrum.

[0046] Figure 18 H NMR spectrum of the amino acid ester compound synthesized for Example 9 13 H NMR spectrum.

[0047] Figure 19 H NMR spectrum of the amino acid ester compound synthesized for Example 10 1 H NMR spectrum.

[0048] Figure 20 H NMR spectrum of the amino acid ester compound synthesized for Example 10 13 H NMR spectrum.

[0049] Figure 21 The carbamate alkenyl ester compound synthesized in Example 11 1 H NMR spectrum.

[0050] Figure 22 The carbamate alkenyl ester compound synthesized in Example 11 13 C10 NMR spectrum.

[0051] Figure 23 The carbamate-based ester compounds synthesized in Example 12 1 H NMR spectrum.

[0052] Figure 24 The carbamate-based ester compounds synthesized in Example 12 13 C10 NMR spectrum. Detailed Implementation

[0053] The present invention will be further explained and described below with reference to specific embodiments.

[0054] Example 1:

[0055] A method for synthesizing an alkenyl carbamate compound, comprising the following steps:

[0056] 0.1 mmol of 1-[4-methylphenylethynyl]-1,2-benzioyl-3(1H)-one and 0.0025 mmol of bis(triphenylphosphine)palladium dichloride were added to a 25 mL Shrek tube equipped with a magnetic stir bar. The Shrek tube was then evacuated and the atmosphere inside was replaced three times with carbon dioxide until the carbon dioxide pressure inside the tube reached 1 atm. Then, 0.2 mmol of 1,8-diazabicyclo[5.4.0]undec-7-ene and 0.2 mmol of diethylamine were dissolved in 1.0 mL of N,N-dimethylformamide and injected using a syringe. The solution was transferred to a Shrek tube, and 0.12 mmol of formic acid was dissolved in 1.0 mL of N,N-dimethylformamide and injected into the Shrek tube using a syringe. The mixture was stirred at 60 °C for 1 h, and then the stirring was stopped. 20 mL of saturated sodium chloride solution was added to quench the reaction. The mixture was extracted with ethyl acetate (3 × 15 mL), and the organic layer was dried over anhydrous sodium sulfate. The mixture was filtered, and the filtrate was concentrated under reduced pressure and then purified by column chromatography. The eluent used for column chromatography was a mixed solvent of petroleum ether and ethyl acetate in a volume ratio of 50:1, which yielded carbamate alkenyl ester compounds (yield: 91%).

[0057] The proton NMR spectrum of the carbamate ester compounds synthesized in this embodiment ( 1 H NMR (image) Figure 1 As shown, carbon NMR spectrum ( 13 (C NMR) image as followsFigure 2 The results are shown in the table below.

[0058] Spectrum analysis:

[0059] 1 H NMR (400 MHz, CDC13): δ = 7.39 (d, J = 8.4 Hz, 2H), 7.15 (d, J = 8.0 Hz, 2H), 5.37 (d, J = 2.0 Hz, 1H), 4.99 (d, J = 2.0 Hz, 1H), 3.46 (q, J = 7.2 Hz, 2H), 3.36 (q, J = 7.2 Hz, 2H), 2.35 (s, 3H), 1.27 (t, J = 7.2 Hz, 3H), 1.18 (t, J = 7.2 Hz, 3H).

[0060] 13 C NMR (100 MHz, CDC13): δ = 153.7, 153.4, 138.3, 132.3, 128.9, 124.6, 100.3, 41.9, 41.6, 21.0, 14.1, 13.2.

[0061] The infrared test data of the amino acid ester compound synthesized in this example are as follows:

[0062] IR (KBr): 2976, 2931, 2877, 1718, 1638, 1512, 1466, 1419, 1378, 1254, 1156, 1092, 1050, 980, 821, 757, 633 cm -1 .

[0063] The high-resolution mass spectrum data of the amino acid ester compound synthesized in this example are as follows:

[0064] HRMS-ESI (m / z): calcd for C 14 H 20 NO2[M+H] + : 234.1489; found: 234.1484.

[0065] In conclusion, the structural formula of the amino acid ester compound synthesized in this example is as follows:

[0066]

[0067] Example 2:

[0068] A method for synthesizing an amino acid ester compound, the steps are as follows:

[0069] 0.1 mmol of 1-[4-chlorophenylethynyl]-1,2-benzioyl-3(1H)-one and 0.005 mmol of bis(triphenylphosphine)palladium dichloride were added to a 25 mL Shrek tube equipped with a magnetic stir bar. The Shrek tube was then evacuated and the atmosphere inside was replaced three times with carbon dioxide until the carbon dioxide pressure inside the tube reached 1 atm. Then, 0.2 mmol of 1,8-diazabicyclo[5.4.0]undec-7-ene and 0.2 mmol of diethylamine were dissolved in 1.0 mL of N,N-dimethylformamide and injected into the tube using a syringe. In a Shrek tube, 0.12 mmol of formic acid was dissolved in 1.0 mL of N,N-dimethylformamide and injected into the Shrek tube using a syringe. The mixture was stirred at 60 °C for 1 h, then stirring was stopped, and 20 mL of saturated sodium chloride solution was added to quench the reaction. The mixture was extracted with ethyl acetate (3 × 15 mL), and the organic layer was dried over anhydrous sodium sulfate. After filtration, the filtrate was concentrated under reduced pressure and then purified by column chromatography. The eluent used for column chromatography was a mixed solvent of petroleum ether and ethyl acetate in a volume ratio of 50:1, which yielded carbamate alkenyl ester compounds (yield: 91%).

[0070] The proton NMR spectrum of the carbamate ester compounds synthesized in this embodiment ( 1 H NMR (image) Figure 3 As shown, carbon NMR spectrum ( 13 (C NMR) image as follows Figure 4 As shown.

[0071] Spectral analysis:

[0072] 1 H NMR (400MHz, CDCl3): δ=7.41-7.38(m,2H),7.32-7.28(m,2H),5.38(d,J=2.4Hz,1H),5.04(d,J=2.4 Hz, 1H), 3.44 (q, J = 7.2Hz, 2H), 3.34 (q, J = 7.2Hz, 2H), 1.25 (t, J = 7.2Hz, 3H), 1.16 (t, J = 7.2Hz, 3H).

[0073] 13 C NMR (100MHz, CDCl3): δ = 153.6, 152.5, 134.4, 133.8, 128.5, 126.2, 101.9, 42.1, 41.7, 14.2, 13.2.

[0074] The infrared test data of the carbamate alkenyl ester compounds synthesized in this embodiment are as follows:

[0075] IR(KBr): 2977,2933,2882,1718,1639,1481,1421,1254,1156,1094,981,833,764cm -1 .

[0076] The high-resolution mass spectrometry data of the carbamate alkenyl ester compounds synthesized in this embodiment are as follows:

[0077] HRMS-ESI(m / z): calcd for C 13 H 17 ClNO2[M+H] + :254.0942; found:254.0938.

[0078] In summary, the structural formula of the carbamate alkenyl ester compound synthesized in this embodiment is as follows:

[0079]

[0080] Example 3:

[0081] A method for synthesizing an alkenyl carbamate compound, comprising the following steps:

[0082] 0.1 mmol of 1-[4-phenylphenylethynyl]-1,2-benzioyl-3(1H)-one and 0.005 mmol of bis(triphenylphosphine)palladium dichloride were added to a 25 mL Shrek tube equipped with a magnetic stir bar. The Shrek tube was then evacuated and the atmosphere inside was replaced three times with carbon dioxide until the carbon dioxide pressure inside the tube reached 1 atm. Then, 0.2 mmol of 1,8-diazabicyclo[5.4.0]undec-7-ene and 0.2 mmol of diethylamine were dissolved in 1.0 mL of N,N-dimethylformamide and injected using a syringe. The solution was transferred to a Shrek tube, and 0.2 mmol of formic acid was dissolved in 1.0 mL of N,N-dimethylformamide and injected into the Shrek tube using a syringe. The mixture was stirred at 60 °C for 1 h, and then the stirring was stopped. 20 mL of saturated sodium chloride solution was added to quench the reaction. The mixture was extracted with ethyl acetate (3 × 15 mL), and the organic layer was dried over anhydrous sodium sulfate. The mixture was filtered, and the filtrate was concentrated under reduced pressure and then purified by column chromatography. The eluent used for column chromatography was a mixed solvent of petroleum ether and ethyl acetate in a volume ratio of 50:1, which yielded carbamate alkenyl ester compounds (yield: 93%).

[0083] The proton NMR spectrum of the carbamate ester compounds synthesized in this embodiment ( 1 H NMR (image) Figure 5 As shown, carbon NMR spectrum ( 13 (C NMR) image as follows Figure 6 As shown.

[0084] Spectrum analysis:

[0085] 1 H NMR (400 MHz, CDC13): δ = 7.62-7.60 (m, 2H), 7.59-7.56 (m, 4H), 7.47-7.43 (m, 2H), 7.38-7.34 (m, 2H), 5.49 (d, J = 2.4 Hz, 1H), 5.08 (d, J = 2.4 Hz, 1H), 3.50 (q, J = 7.2 Hz, 2H), 3.39 (q, J = 7.2 Hz, 2H), 1.33-1.29 (m, 3H), 1.21 (t, J = 6.4 Hz, 3H).

[0086] 13 C NMR (100 MHz, CDC13): δ = 153.8, 153.2, 141.4, 140.5, 134.1, 128.7, 127.4, 127.1, 127.0, 125.3, 101.4, 42.0, 41.8, 14.3, 13.3.

[0087] The infrared test data of the amino acid ester compound synthesized in this example are as follows:

[0088] IR (KBr): 2976, 2930, 2880, 1716, 1644, 1474, 1418, 1255, 1156, 1093, 980, 845, 765, 695 cm -1 .

[0089] The high resolution mass spectrum data of the amino acid ester compound synthesized in this example are as follows:

[0090] HRMS-ESI (m / z): calcd for C 19 H 22 NO2[M+H] + : 296.1645; found: 296.1638.

[0091] In conclusion, the structural formula of the amino acid ester compound synthesized in this example is as follows:

[0092]

[0093] Example 4:

[0094] A method for synthesizing an amino acid ester compound, the steps are as follows:

[0095] Into a 25 mL Schlenk tube equipped with a magnetic stirrer, 0.1 mmol of 1-[4-methylphenyl-ethynyl]-1,2-benziodoxol-3(lH)-one and 0.005 mmol of palladium dichloride bis(triphenylphosphine) were introduced, the Schlenk tube was vacuumed and then filled with carbon dioxide three times to replace the atmosphere in the tube, and then the pressure of carbon dioxide in the tube was adjusted to 1 atm. Then 0.3 mmol of 1,8-diazabicyclo[5.4.0]undec-7-ene and 0.3 mmol of dimethylamine were dissolved in 1.0 mL of N,N-dimethylformamide and injected into the Schlenk tube using a syringe. Then 0.12 mmol of formic acid was dissolved in 1.0 mL of N,N-dimethylformamide and injected into the Schlenk tube using a syringe. The Schlenk tube was stirred at 70°C for 3 h, and then the stirring was stopped, 20 mL of saturated sodium chloride solution was added to quench the reaction, and the organic layer was extracted with ethyl acetate (3 x 15 mL), dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by column chromatography using a mixture of petroleum ether and ethyl acetate (50:1 by volume) as the eluent to obtain the amino acid ester compound (yield: 86%).

[0096] The nuclear magnetic resonance hydrogen spectrum (H NMR) of the amino acid ester compound synthesized in this example is shown in 1 Figure 1. Figure 7 The nuclear magnetic resonance carbon spectrum (C NMR) of the amino acid ester compound synthesized in this example is shown in 13 Figure 2. Figure 8

[0097] Spectrum analysis:

[0098] 1 H NMR (400 MHz, CDCl3): δ = 7.37 (d, J = 8.0 Hz, 2H), 7.15 (d, J = 8.0 Hz, 2H), 5.37 (d, J = 2.0 Hz, 1H), 4.98 (d, J = 2.0 Hz, 1H), 3.12 (s, 3H), 2.97 (s, 3H), 2.34 (s, 3H).

[0099] 13 C NMR (100 MHz, CDCl3): δ = 154.5, 153.4, 138.6, 132.2, 129.1, 124.7, 100.6, 36.6, 36.3, 21.1.

[0100] The infrared test data of the amino acid ester compound synthesized in this example are as follows:

[0101] IR (KBr): 2929, 1722, 1649, 1611, 1390, 1261, 1166, 1094, 1025, 926, 856, 820, 755 cm​-1 .

[0102] The high-resolution mass spectrometry data of the carbamate alkenyl ester compounds synthesized in this embodiment are as follows:

[0103] HRMS-ESI(m / z): calcd for C 12 H 16 NO2[M+H] + :206.1176; found:206.1172.

[0104] In summary, the structural formula of the carbamate alkenyl ester compound synthesized in this embodiment is as follows:

[0105]

[0106] Example 5:

[0107] A method for synthesizing an alkenyl carbamate compound, comprising the following steps:

[0108] 0.1 mmol of 1-[4-methylphenylethynyl]-1,2-benzioyl-3(1H)-one and 0.005 mmol of bis(triphenylphosphine)palladium dichloride were added to a 25 mL Shrek tube equipped with a magnetic stir bar. The Shrek tube was then evacuated and the atmosphere inside was replaced three times with carbon dioxide until the carbon dioxide pressure inside the tube reached 1 atm. Then, 0.2 mmol of 1,8-diazabicyclo[5.4.0]undec-7-ene and 0.2 mmol of di-n-butylamine were dissolved in 1.0 mL of dimethyl sulfoxide and injected using a syringe. The solution was transferred to a Shrek tube, and 0.12 mmol of formic acid was dissolved in 1.0 mL of dimethyl sulfoxide and injected into the Shrek tube using a syringe. The mixture was stirred at 60 °C for 1 h, and then the stirring was stopped. The reaction was quenched by adding 20 mL of saturated sodium chloride solution. The mixture was extracted with ethyl acetate (3 × 15 mL), and the organic layer was dried over anhydrous sodium sulfate. The mixture was filtered, and the filtrate was concentrated under reduced pressure and then purified by column chromatography. The eluent used for column chromatography was a mixed solvent of petroleum ether and ethyl acetate in a volume ratio of 50:1, which yielded carbamate alkenyl ester compounds (yield: 84%).

[0109] The proton NMR spectrum of the carbamate ester compounds synthesized in this embodiment ( 1 H NMR (image) Figure 9 As shown, carbon NMR spectrum ( 13 (C NMR) image as follows Figure 10 As shown.

[0110] Spectral analysis:

[0111] 1H NMR (400 MHz, CDC13): δ = 7.38-7.35 (m, 2H), 7.16-7.14 (m, 2H), 5.35 (d, J = 2.0 Hz, 1H), 4.96 (d, J = 2.0 Hz, 1H), 3.38 (t, J = 7.6 Hz, 2H), 3.28 (t, J = 7.6 Hz, 2H), 2.34 (s, 3H), 1.69-1.64 (m, 2H), 1.58-1.53 (m, 2H), 1.42-1.36 (m, 2H), 1.35-1.30 (m, 2H), 0.98 (t, J = 7.2 Hz, 3H), 0.93 (t, J = 7.2 Hz, 3H).

[0112] 13 C NMR (100 MHz, CDC13): δ = 154.2, 153.6, 138.4, 132.5, 129.0, 124.8, 100.3, 47.3, 47.1, 30.9, 30.0, 21.1, 20.0, 13.8.

[0113] The infrared test data of the amino acid ester compound synthesized in this example are as follows:

[0114] IR (KBr): 2953, 2866, 1718, 1658, 1601, 1260, 1216, 1151, 1097, 819 cm -1 .

[0115] The high resolution mass spectrum data of the amino acid ester compound synthesized in this example are as follows:

[0116] HRMS-ESI (m / z): calcd for C 18 H 28 NO2[M+H] + : 290.2115; found: 290.2108.

[0117] In conclusion, the structural formula of the amino acid ester compound synthesized in this example is as follows:

[0118]

[0119] Example 6:

[0120] A method for synthesizing an amino acid ester compound, the steps are as follows:

[0121] 0.1 mmol of 1-[4-methylphenylethynyl]-1,2-benzyl-3(1H)-one and 0.005 mmol of bis(triphenylphosphine)palladium dichloride were added to a 25 mL Shrek tube equipped with a magnetic stir bar. The Shrek tube was then evacuated and the atmosphere inside was replaced three times with carbon dioxide until the carbon dioxide pressure inside the tube reached 1 atm. Then, 0.3 mmol of 1,8-diazabicyclo[5.4.0]undec-7-ene and 0.3 mmol of dibenzylamine were dissolved in 1.0 mL of N,N-dimethylformamide and injected using a syringe. The solution was transferred to a Shrek tube, and 0.2 mmol of formic acid was dissolved in 1.0 mL of N,N-dimethylformamide and injected into the Shrek tube using a syringe. The mixture was stirred at 70 °C for 1 h, and then the stirring was stopped. 20 mL of saturated sodium chloride solution was added to quench the reaction. The mixture was extracted with ethyl acetate (3 × 15 mL), and the organic layer was dried over anhydrous sodium sulfate. The mixture was filtered, and the filtrate was concentrated under reduced pressure and then purified by column chromatography. The eluent used for column chromatography was a mixed solvent of petroleum ether and ethyl acetate in a volume ratio of 50:1, which yielded carbamate alkenyl ester compounds (yield: 94%).

[0122] The proton NMR spectrum of the carbamate ester compounds synthesized in this embodiment ( 1 H NMR (image) Figure 11 As shown, carbon NMR spectrum ( 13 (C NMR) image as follows Figure 12 As shown.

[0123] Spectral analysis:

[0124] 1 H NMR (400MHz, CDCl3): δ=7.42-7.32(m,12H),7.16(d,J=8.0Hz,2H),5.44(d, J=2.0Hz,1H),5.08(d,J=2.0Hz,1H),4.62(s,2H),4.56(s,2H),2.38(s,3H).

[0125] 13 C NMR (100MHz, CDCl3): δ=154.9,153.6,138.7,137.0,132.1,129.1,128.7,128.6,128.3,127.5,127.4,124.9,100.9,49.9,49.4,21.2.

[0126] The infrared test data of the carbamate alkenyl ester compounds synthesized in this embodiment are as follows:

[0127] IR(KBr): 3030,2922,2853,1718,1634,1498,1453,1415,1362,1265,1219,1102,930,864,820,752,699cm -1 .

[0128] The high-resolution mass spectrometry data of the carbamate alkenyl ester compounds synthesized in this embodiment are as follows:

[0129] HRMS-ESI(m / z): calcd for C 24 H 24 NO2[M+H] + :358.1802; found:358.1796.

[0130] In summary, the structural formula of the carbamate alkenyl ester compound synthesized in this embodiment is as follows:

[0131]

[0132] Example 7:

[0133] A method for synthesizing an alkenyl carbamate compound, comprising the following steps:

[0134] 0.1 mmol of 1-[4-methylphenylethynyl]-1,2-benzioyl-3(1H)-one and 0.005 mmol of bis(triphenylphosphine)palladium dichloride were added to a 25 mL Shrek tube equipped with a magnetic stir bar. The Shrek tube was then evacuated and the atmosphere inside was replaced three times with carbon dioxide until the carbon dioxide pressure inside the tube reached 1 atm. Then, 0.2 mmol of 1,8-diazabicyclo[5.4.0]undec-7-ene and 0.2 mmol of N-methylcyclohexylamine were dissolved in 1.0 mL of N,N-dimethylformamide and injected using a syringe. Inject the solution into a Shrek tube, then dissolve 0.12 mmol of formic acid in 1.0 mL of N,N-dimethylformamide and inject the solution into the Shrek tube using a syringe. Stir at 60 °C for 1 h, then stop stirring and add 20 mL of saturated sodium chloride solution to quench the reaction. Extract with ethyl acetate (3 × 15 mL), dry the organic layer with anhydrous sodium sulfate, filter, concentrate the filtrate under reduced pressure, and then purify by column chromatography. The eluent used for column chromatography purification is a mixed solvent of petroleum ether and ethyl acetate in a volume ratio of 50:1, which yields carbamate alkenyl ester compounds (yield: 84%).

[0135] The proton NMR spectrum of the carbamate ester compounds synthesized in this embodiment ( 1 H NMR (image) Figure 13 As shown, carbon NMR spectrum ( 13 (C NMR) image as followsFigure 14

[0136] Spectral analysis:

[0137] 1 H NMR (400 MHz, CDC13): δ = 7.36 (d, J = 8.0 Hz, 2H), 7.15 (d, J = 8.0 Hz, 2H), 5.36 (d, J = 6.0 Hz, 1H), 4.98 (d, J = 2.0 Hz, 1H), 4.09-3.96 (m, 1H), 2.97-2.85 (m, 3H), 2.34 (s, 3H), 1.88-1.64 (m, 5H), 1.53-1.33 (m, 4H), 1.14-1.07 (m, 1H).

[0138] 13 C NMR (100 MHz, CDC13): δ = 154.1, 153.6, 138.5, 132.4, 129.1, 124.7, 100.5, 100.4, 55.6, 55.1, 30.7, 30.0, 28.6, 25.7, 25.6, 25.4, 21.1.

[0139] The infrared test data of the amino acid ester compound synthesized in this example are as follows:

[0140] IR (KBr): 2929, 2857, 1716, 1608, 1511, 1447, 1404, 1365, 1318, 1264, 1155, 1110, 993, 932, 822, 754 cm -1 .

[0141] The high-resolution mass spectrum data of the amino acid ester compound synthesized in this example are as follows:

[0142] HRMS-ESI (m / z): calcd for C 17 H 24 NO2[M+H] + : 274.1802; found: 274.1796.

[0143] In summary, the structural formula of the amino acid ester compound synthesized in this example is as follows:

[0144]

[0145] Example 8:

[0146] A method for synthesizing an amino acid ester compound, the steps are as follows:

[0147] ​Into a 25 mL Schlenk tube equipped with a magnetic stir bar, was placed 0.1 mmol of 1-[4-methylphenyl ethynyl]-1,2-benzoiodoxole-3(lH)-one and 0.005 mmol of palladium tetrakis(triphenylphosphine). The Schlenk tube was evacuated and backfilled with carbon dioxide three times to replace the atmosphere. The carbon dioxide pressure was then brought to 1 atm. Into the Schlenk tube was then injected 0.2 mmol of 1,8-diazabicyclo[5.4.0]undec-7-ene and 0.2 mmol of N-methylbenzylamine in 1.0 mL of N,N-dimethylformamide. Then, 0.12 mmol of formic acid in 1.0 mL of N,N-dimethylformamide was injected into the Schlenk tube. The mixture was stirred at 60 °C for 1 h. The reaction was quenched by the addition of 20 mL of saturated sodium chloride solution. The organic layer was extracted with ethyl acetate (3 x 15 mL), dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by column chromatography using a mixture of petroleum ether and ethyl acetate (50:1, by volume) as the eluent to give the amino acid alkyl ester compound (yield: 91%).

[0148] The H NMR spectrum of the amino acid alkyl ester compound synthesized in this example is shown in 1 Figure 15 The C NMR spectrum of the amino acid alkyl ester compound synthesized in this example is shown in 13 Figure 16

[0149] Spectrum analysis:

[0150] 1 H NMR (400 MHz, CDC13): δ = 7.42-7.39 (m, 2H), 7.36-7.30 (m, 5H), 7.19-7.12 (m, 2H), 5.41 (d, J = 6.8 Hz, 1H), 5.06-5.01 (m, 1H), 4.68-4.54 (m, 2H), 3.05-2.99 (m, 3H), 2.37-2.35 (m, 3H).

[0151] 13 C NMR (100 MHz, CDC13): δ = 154.8, 154.4, 153.5, 138.6, 137.1, 132.2, 129.1, 129.0, 128.7, 128.6, 128.0, 127.5, 127.2, 124.9, 124.8, 100.8, 100.7, 52.8, 52.7, 34.8, 33.9, 21.2.

[0152] The infrared test data of the amino acid alkyl ester compound synthesized in this example are as follows:​​​

[0153] IR (KBr): 154.8, 154.4, 153.5, 138.6, 137.1, 132.2, 129.1, 129.0, 128.7, 128.6, 128.0, 127.5, 127.2, 124.9, 124.8, 100.8, 100.7, 52.8, 52.7, 34.8, 33.9, 21.2 cm -1 .

[0154] The high resolution mass spectrum data of the amino acid ester compound synthesized in this example is as follows:

[0155] HRMS-ESI (m / z): calcd for C 18 H 20 NO2[M+H] + :282.1489;found:282.1484.

[0156] In summary, the structural formula of the amino acid ester compound synthesized in this example is as follows:

[0157]

[0158] Example 9:

[0159] A method for synthesizing an amino acid ester compound, the steps are as follows:

[0160] 0.1 mmol of 1-[4-methylphenylacetylene]-1,2-benziodoxol-3(1H)-one and 0.005 mmol of dichlorobis(triphenylphosphine)palladium were added to a Schlenk tube with a volume of 25 mL with a magnetic stirrer, then the Schlenk tube was vacuumized and replaced with carbon dioxide three times to replace the atmosphere in the tube, then the pressure of carbon dioxide in the tube was 1 atm, then 0.2 mmol of 1,8-diazabicyclo[5.4.0]undec-7-ene and 0.2 mmol of N-ethyl-n-propylamine were dissolved in 1.0 mL of N,N-dimethylformamide and injected into the Schlenk tube with a syringe, then 0.12 mmol of formic acid was dissolved in 1.0 mL of N,N-dimethylformamide and injected into the Schlenk tube with a syringe, then stirred at 60°C for 1 h, then stopped stirring, added 20 mL of saturated sodium chloride solution to quench the reaction, extracted with ethyl acetate (3×15 mL), dried the organic layer with anhydrous sodium sulfate, filtered, concentrated the filtrate under reduced pressure, and then purified by column chromatography, the eluent used in column chromatography was a mixture of petroleum ether and ethyl acetate in a volume ratio of 50:1, to obtain the amino acid ester compound (yield: 93%).

[0161] The H NMR spectrum of the amino acid ester compound synthesized in this example is shown in 1 The C NMR spectrum of the amino acid ester compound synthesized in this example is shown in Figure 17 13 Figure 18

[0162] Spectrum analysis:

[0163] 1 H NMR (400 MHz, CDCl3): δ = 7.37 (d, J = 8.4 Hz, 2H), 7.15 (d, J = 7.6 Hz, 2H), 5.36 (d, J = 2.0 Hz, 1H), 4.97 (d, J = 2.4 Hz, 1H), 3.48-3.23 (m, 4H), 2.34 (s, 3H), 1.71-1.58 (m, 2H), 1.29-1.15 (m, 3H), 1.00-0.89 (m, 3H).

[0164] 13 C NMR (100 MHz, CDCl3): δ = 154.0, 153.6, 138.5, 132.5, 129.0, 124.8, 100.4, 48.9, 48.7, 42.4, 42.1, 22.1, 21.3, 21.1, 14.1, 13.1, 11.2, 11.1.

[0165] The infrared test data of the amino acid ester compound synthesized in this example are as follows:

[0166] IR (KBr): 2967, 2931, 2874, 1719, 1641, 1512, 1465, 1379, 1245, 1155, 1095, 1021, 968, 819, 755 cm -1 .

[0167] The high resolution mass spectrum data of the amino acid ester compound synthesized in this example are as follows:

[0168] HRMS-ESI (m / z): calcd for C 15 H 22 NO2[M+H] + : 248.1645; found: 248.1640.

[0169] In summary, the structural formula of the amino acid ester compound synthesized in this example is as follows:

[0170]

[0171] Example 10: ​​​

[0172] A method for synthesizing an alkenyl carbamate compound, comprising the following steps:

[0173] 0.1 mmol of 1-[4-methylphenylethynyl]-1,2-benzioyl-3(1H)-one and 0.005 mmol of bis(triphenylphosphine)palladium dichloride were added to a 25 mL Shrek tube equipped with a magnetic stir bar. The Shrek tube was then evacuated and the atmosphere inside was replaced three times with carbon dioxide until the carbon dioxide pressure inside the tube reached 1 atm. Then, 0.2 mmol of 1,8-diazabicyclo[5.4.0]undec-7-ene and 0.2 mmol of thiomorpholine were dissolved in 1.0 mL of N,N-dimethylformamide and injected using a syringe. The solution was transferred to a Shrek tube, and 0.12 mmol of formic acid was dissolved in 1.0 mL of N,N-dimethylformamide and injected into the Shrek tube using a syringe. The mixture was stirred at 60 °C for 1 h, and then the stirring was stopped. The reaction was quenched by adding 20 mL of saturated sodium chloride solution. The mixture was extracted with ethyl acetate (3 × 15 mL), and the organic layer was dried over anhydrous sodium sulfate. The mixture was filtered, and the filtrate was concentrated under reduced pressure and then purified by column chromatography. The eluent used for column chromatography was a mixed solvent of petroleum ether and ethyl acetate in a volume ratio of 50:1, which yielded carbamate alkenyl ester compounds (yield: 85%).

[0174] The proton NMR spectrum of the carbamate ester compounds synthesized in this embodiment ( 1 H NMR (image) Figure 19 As shown, carbon NMR spectrum ( 13 (C NMR) image as follows Figure 20 As shown.

[0175] Spectral analysis:

[0176] 1 H NMR (400MHz, CDCl3): δ = 7.34 (d, J = 8.0Hz, 2H), 7.15 (d, J = 8.4Hz, 2H), 5.38 (d, J = 2.4Hz, 1 H), 4.97 (d, J = 2.4Hz, 1H), 3.94 (s, 2H), 3.79 (s, 2H), 2.67 (d, J = 7.2Hz, 4H), 2.34 (s, 3H).

[0177] 13 C NMR (100MHz, CDCl3): δ = 153.3, 153.0, 138.8, 132.0, 129.1, 124.7, 100.9, 47.1, 46.4, 27.5, 27.1, 21.1.

[0178] The infrared test data of the carbamate alkenyl ester compounds synthesized in this embodiment are as follows:

[0179] IR(KBr): 2916,1717,1638,1424,1281,1201,1095,964,826,746,550cm -1 .

[0180] The high-resolution mass spectrometry data of the carbamate alkenyl ester compounds synthesized in this embodiment are as follows:

[0181] HRMS-ESI(m / z): calcd for C 14 H 18 NO2S[M+H] + :264.1058; found:264.1047.

[0182] In summary, the structural formula of the carbamate alkenyl ester compound synthesized in this embodiment is as follows:

[0183]

[0184] Example 11:

[0185] A method for synthesizing an alkenyl carbamate compound, comprising the following steps:

[0186] 0.1 mmol of 1-[4-methylphenylethynyl]-1,2-benzioyl-3(1H)-one and 0.005 mmol of bis(triphenylphosphine)palladium dichloride were added to a 25 mL Shrek tube equipped with a magnetic stir bar. The Shrek tube was then evacuated and the atmosphere inside was replaced three times with carbon dioxide until the carbon dioxide pressure inside the tube reached 1 atm. Then, 0.2 mmol of 1,8-diazabicyclo[5.4.0]undec-7-ene and 0.2 mmol of tetrahydropyrrole were dissolved in 1.0 mL of N,N-dimethylformamide and injected using a syringe. The solution was injected into a Shrek tube, and 0.2 mmol of formic acid was dissolved in 1.0 mL of N,N-dimethylformamide and injected into the Shrek tube using a syringe. The mixture was stirred at 60 °C for 1 h, and then the stirring was stopped. The reaction was quenched by adding 20 mL of saturated sodium chloride solution. The mixture was extracted with ethyl acetate (3 × 15 mL), and the organic layer was dried over anhydrous sodium sulfate. The mixture was filtered, and the filtrate was concentrated under reduced pressure and then purified by column chromatography. The eluent used for column chromatography was a mixed solvent of petroleum ether and ethyl acetate in a volume ratio of 50:1, which yielded carbamate alkenyl ester compounds (yield: 91%).

[0187] The proton NMR spectrum of the carbamate ester compounds synthesized in this embodiment ( 1 H NMR (image) Figure 21 As shown, carbon NMR spectrum ( 13 (C NMR) image as followsFigure 22

[0188] Spectrum analysis:

[0189] 1 H NMR (400 MHz, CDC13): δ = 7.40-7.38 (m, 2H), 7.16-7.12 (m, 2H), 5.37 (d, J = 1.6 Hz, 1H), 5.01 (d, J = 1.6 Hz, 1H), 3.58 (t, J = 6.8 Hz, 2H), 3.44 (t, J = 6.8 Hz, 2H), 2.34 (s, 3H), 1.98-1.88 (m, 4H).

[0190] 13 C NMR (100 MHz, CDC13): δ = 153.2, 152.8, 138.5, 132.4, 129.0, 124.8, 100.4, 46.3, 46.2, 25.8, 24.9, 21.1.

[0191] The infrared test data of the amino acid ester compound synthesized in this example are as follows:

[0192] IR (KBr): 2977, 2876, 1720, 1650, 1610, 1403, 1264, 1175, 1098, 1020, 819, 750 cm -1 .

[0193] The high-resolution mass spectrum data of the amino acid ester compound synthesized in this example are as follows:

[0194] HRMS-ESI (m / z): calcd for C 14 H 18 NO2[M+H] + : 232.1332; found: 232.1330.

[0195] In summary, the structural formula of the amino acid ester compound synthesized in this example is as follows:

[0196]

[0197] Example 12:

[0198] A method for synthesizing an amino acid ester compound, the steps are as follows:

[0199] ​0.1 mmol of 1-[4-methylphenylethynyl]-1,2-benzioyl-3(1H)-one and 0.005 mmol of bis(triphenylphosphine)palladium dichloride were added to a 25 mL Shrek tube equipped with a magnetic stir bar. The Shrek tube was then evacuated and the atmosphere inside was replaced three times with carbon dioxide until the carbon dioxide pressure inside the tube reached 1 atm. Then, 0.3 mmol of 1,8-diazabicyclo[5.4.0]undec-7-ene and 0.3 mmol of N-methylpiperazine were dissolved in 1.0 mL of N,N-dimethylformamide and injected using a syringe. The solution was injected into a Shrek tube, and 0.12 mmol of formic acid was dissolved in 1.0 mL of N,N-dimethylformamide and injected into the Shrek tube using a syringe. The mixture was stirred at 60 °C for 1 h, and then the stirring was stopped. The reaction was quenched by adding 20 mL of saturated sodium chloride solution. The mixture was extracted with ethyl acetate (3 × 15 mL), and the organic layer was dried over anhydrous sodium sulfate. The mixture was filtered, and the filtrate was concentrated under reduced pressure and then purified by column chromatography. The eluent used for column chromatography was a mixed solvent of petroleum ether and ethyl acetate in a volume ratio of 50:1, which yielded carbamate alkenyl ester compounds (yield: 94%).

[0200] The proton NMR spectrum of the carbamate ester compounds synthesized in this embodiment ( 1 H NMR (image) Figure 23 As shown, carbon NMR spectrum ( 13 (C NMR) image as follows Figure 24 As shown.

[0201] Spectral analysis:

[0202] 1 H NMR (400MHz, CDCl3): δ=7.35 (d, J=8.0Hz, 2H), 7.15 (d, J=8.0Hz, 2H), 5.37 (d, J=2.0 Hz, 1H), 4.97 (d, J = 2.0Hz, 1H), 3.70 (s, 2H), 3.54 (s, 2H), 2.44 (s, 4H), 2.33 (s, 6H).

[0203] 13 C NMR (100MHz, CDCl3): δ=153.4,153.3,138.7,132.1,129.2,124.8,100.8,54.9,54.6,46.1,44.4,43.8,21.2.

[0204] The infrared test data of the carbamate alkenyl ester compounds synthesized in this embodiment are as follows:

[0205] IR (KBr): 2856, 1650, 1610, 1367, 1228, 1099, 1000, 773, 743 cm -1 .

[0206] The high resolution mass spectrum data of the amino acid ester compound synthesized in this example is as follows:

[0207] HRMS-ESI (m / z): calcd for C 15 H 21 N2O2[M+H] + : 261.1598; found: 261.1595.

[0208] As can be seen from the above, the structural formula of the amino acid ester compound synthesized in this example is as follows:

[0209]

[0210] The above examples are the preferred embodiments of the present application, but the embodiments of the present application are not limited to the above examples, and any changes, modifications, substitutions, combinations, simplifications made without departing from the spirit and principles of the present application are equivalent replacement methods and are included in the protection scope of the present application.

Claims

1. A method for synthesizing an alkenyl carbamate compound, characterized in that, The process includes the following steps: dispersing an alkynyl hypervalent iodine compound, a palladium catalyst, an amine, formic acid, and a base in a solvent, then introducing carbon dioxide to react and obtain an alkenyl carbamate compound; the structural formula of the alkynyl hypervalent iodine compound is: In the formula, R 1 It can be hydrogen, fluorine, chlorine, bromine, methyl, ethyl, methoxy, trifluoromethyl, cyano, -CHO, phenyl, One of them; the palladium catalyst is bis(triphenylphosphine)palladium dichloride; the amine is One of thiomorpholine, tetrahydropyrrole, hexahydropyridine, morpholine, and N-methylpiperazine, wherein R 2 and R 3 Independently, it is one of methyl, ethyl, n-propyl, n-butyl, cyclohexyl, and benzyl; the base is 1,8-diazabicyclo[5.4.0]undec-7-ene.

2. The synthesis method according to claim 1, characterized in that: The molar ratio of the alkynyl high-valent iodine compound, amine, and formic acid is 1:2-3:1.2-2.

0.

3. The synthesis method according to claim 1 or 2, characterized in that: The molar ratio of the alkyne-based high-valent iodine compound to the palladium catalyst is 1:0.025 to 0.

05.

4. The synthesis method according to claim 1 or 2, characterized in that: The molar ratio of the alkyne-based high-valent iodine compound to the base is 1:2 to 3.

5. The synthesis method according to claim 1 or 2, characterized in that: The solvent is at least one selected from N,N-dimethylformamide, N,N-dimethylacetamide, acetonitrile, dimethyl sulfoxide, and tetrahydrofuran.

6. The synthesis method according to claim 1 or 2, characterized in that: The reaction was carried out under conditions of carbon dioxide pressure of 0.8 atm to 1.2 atm and temperature of 50°C to 70°C for 1 to 3 hours.

7. The synthesis method according to claim 1 or 2, characterized in that: After the reaction was completed, the reaction product was purified by column chromatography.

8. The synthesis method according to claim 7, characterized in that: The column chromatography purification uses a mixed solvent of petroleum ether and ethyl acetate in a volume ratio of 20 to 50:1.

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