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CAS No. : | 931-23-7 | MDL No. : | MFCD15145822 |
Formula : | C5H6O3 | Boiling Point : | - |
Linear Structure Formula : | - | InChI Key : | HQIZYPQNJWENRT-UHFFFAOYSA-N |
M.W : | 114.10 | Pubchem ID : | 5279300 |
Synonyms : |
|
Num. heavy atoms : | 8 |
Num. arom. heavy atoms : | 0 |
Fraction Csp3 : | 0.4 |
Num. rotatable bonds : | 0 |
Num. H-bond acceptors : | 3.0 |
Num. H-bond donors : | 1.0 |
Molar Refractivity : | 26.01 |
TPSA : | 46.53 Ų |
GI absorption : | High |
BBB permeant : | No |
P-gp substrate : | No |
CYP1A2 inhibitor : | No |
CYP2C19 inhibitor : | No |
CYP2C9 inhibitor : | No |
CYP2D6 inhibitor : | No |
CYP3A4 inhibitor : | No |
Log Kp (skin permeation) : | -6.97 cm/s |
Log Po/w (iLOGP) : | 1.06 |
Log Po/w (XLOGP3) : | 0.04 |
Log Po/w (WLOGP) : | -0.19 |
Log Po/w (MLOGP) : | -0.08 |
Log Po/w (SILICOS-IT) : | 0.39 |
Consensus Log Po/w : | 0.24 |
Lipinski : | 0.0 |
Ghose : | None |
Veber : | 0.0 |
Egan : | 0.0 |
Muegge : | 1.0 |
Bioavailability Score : | 0.55 |
Log S (ESOL) : | -0.57 |
Solubility : | 30.5 mg/ml ; 0.268 mol/l |
Class : | Very soluble |
Log S (Ali) : | -0.57 |
Solubility : | 30.7 mg/ml ; 0.269 mol/l |
Class : | Very soluble |
Log S (SILICOS-IT) : | 0.11 |
Solubility : | 146.0 mg/ml ; 1.28 mol/l |
Class : | Soluble |
PAINS : | 0.0 alert |
Brenk : | 0.0 alert |
Leadlikeness : | 1.0 |
Synthetic accessibility : | 2.72 |
Signal Word: | Warning | Class: | |
Precautionary Statements: | P261-P280-P301+P312-P302+P352-P305+P351+P338 | UN#: | |
Hazard Statements: | H302-H315-H319-H335 | Packing Group: | |
GHS Pictogram: |
* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
60% | With lithium tri-t-butoxyaluminum hydride In tetrahydrofuran at -30 - -15℃; for 3 h; Inert atmosphere | A solution of 5.34 g LiAlH(t-BuO)3 (21.00 mmol) in 40 cm3 anhydrous THF was added dropwise over a 30-min period to a solution of 1.68 g citraconic anhydride (6, 15.00 mmol) in 50 cm3 anhydrous THF under a nitrogen atmosphere at - 30 C. The temperature was maintained at - 15 C for 3 h and then the reaction mixture was warmed to ambient temperature. The reaction was quenched with 50 cm3 1 M HCl, the solution was saturated with NaCl, the crude product was extracted with EtOAc (3 9 50 cm3), and the combined organic fraction was dried over MgSO4. The solvent was removed in vacuo. Purification by column chromatography (SiO2, 20percent AcOEt in petroleum ether) afforded 7a (1.023 g,60percent) and 7b (116 mg, 7percent) as yellow oils. TLC: Rf = 0.16 (for 7a), 0.15 (for 7b) (20percent AcOEt in petroleum ether). 7a: 1H NMR (400 MHz, acetone-d6): d = 6.67 (bs, 1H),6.02 (bs, 1H), 5.87 (p, J = 1.5 Hz, 1H), 2.08 (d,J = 1.5 Hz, 3H) ppm; 13C NMR (100 MHz, acetone-d6):d = 171.30 ([C\), 166.65 ([C\), 118.68 (CH), 100.25(CH), 13.15 (CH3) ppm; MS (EI): m/z (percent) = 114.0 ([M?],2), 113.0 (7), 86.0 (61), 85.0 (13), 69.0 (100), 68.0 (82),41.1 (50), 40.1 (65), 39.1 (93). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
84% | With thionyl chloride; sodium carbonate In 1,2-dimethoxyethane 1.) 40 deg C, 3 h, 2.) 80 deg C, 1 h; | |
With thionyl chloride; sodium carbonate In diethylene glycol dimethyl ether 1.) 40 deg C, 3 h, 2.) 80 deg C, 1 h; Yields of byproduct given; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
87% | With amberlyst-15; water Ambient temperature; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
91% | With hydrogenchloride at 100℃; for 48h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 3 steps 1: 72 h / 120 °C 2: 83 percent / triethylamine, H2 / 10percent Pd/C / ethyl acetate / 12.5 h / 2068.6 Torr / Ambient temperature 3: 87 percent / lithium aluminum hydride / tetrahydrofuran / 12 h / Ambient temperature |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1: 72 h / 120 °C 2: 83 percent / triethylamine, H2 / 10percent Pd/C / ethyl acetate / 12.5 h / 2068.6 Torr / Ambient temperature |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 4 steps 1: 72 h / 120 °C 2: 83 percent / triethylamine, H2 / 10percent Pd/C / ethyl acetate / 12.5 h / 2068.6 Torr / Ambient temperature 3: 87 percent / lithium aluminum hydride / tetrahydrofuran / 12 h / Ambient temperature 4: 88 percent / pyridine / 6 h / Heating |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
76% | Stage #1: 2-(trimethylsilyl)ethyl2-(diethoxyphosphoryl)acetate With n-butyllithium In tetrahydrofuran; hexane at 0℃; for 0.5h; Stage #2: 5-Hydroxy-3-methyl-5H-furan-2-one In tetrahydrofuran; hexane at 20℃; for 1h; Further stages.; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
88% | Stage #1: Methyl diethylphosphonoacetate With sodium methylate In fenbutrazate at 0℃; for 0.0833333h; Stage #2: 5-Hydroxy-3-methyl-5H-furan-2-one In methanol; diethyl ether at 20℃; for 1h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
76% | Stage #1: 2-(trimethylsilyl)ethyl2-(diethoxyphosphoryl)acetate With n-butyllithium In tetrahydrofuran; hexane at 0℃; for 0.5h; Stage #2: 5-Hydroxy-3-methyl-5H-furan-2-one In tetrahydrofuran; hexane at 20℃; for 1h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
60% | With sulfuric acid In lithium hydroxide monohydrate for 16h; Reflux; | 1 In a pre-dried 250 mL round-bottomed flask, glyoxal (40% wt in water, 1.4 eq) and methylmalonic acid (1 eq) were added sequentially, and dissolved in 90 mL of water. Subsequently, 20d of concentrated sulfuric acid was added to the reaction system and refluxed for 16 h. After the reaction was completed, the reaction system was cooled to room temperature, the reaction system was extracted with ethyl acetate, the collected organic phase was washed with water and saturated brine successively, dried over anhydrous sodium sulfate, and filtered to remove the crude product. The crude product was separated and purified by column chromatography (PE : EA = 2: 1, v/v) to obtain an orange-yellow intermediate 5-hydroxy-3-methylfuran-2-one with a yield of 60%. |
52% | With sulfuric acid In lithium hydroxide monohydrate for 16h; Reflux; | |
51.97% | With sulfuric acid In lithium hydroxide monohydrate for 16h; Reflux; | Weigh methylmalonic acid 10g (84.68mmol) and glyoxal 17.82g (40% aqueous solution, 0.123mol) added to a 250mL round bottom flask, add 100mL of water, magnetic stirring to dissolve, slowly add concentrated H2SO4 1.12mL under stirring, heat reflux for reaction. TLC [V petroleum ether: ethyl V acetate = 3:2] monitoring reaction, 16h after the end of the reaction, ethyl acetate extracted 30mL×3, combined organic phase, anhydrous sodium sulfate drying, filtration, reduced pressure concentration, purified by column chromatography, V petroleum ether: ethyl V acetate = 2:1, to give 5-hydroxy-3-methyl-2-(5H)-furone, a yellow solid, yield: 51.97%. |
51.97% | With sulfuric acid In lithium hydroxide monohydrate for 16h; Reflux; | Weigh methylmalonic acid 10g (84.68mmol) and glyoxal 17.82g (40% aqueous solution, 0.123mol) added to a 250mL round bottom flask, add 100mL of water, magnetic stirring to dissolve, slowly add concentrated H2SO4 1.12mL under stirring, heat reflux for reaction. TLC [V petroleum ether: ethyl V acetate = 3:2] monitoring reaction, 16h after the end of the reaction, ethyl acetate extracted 30mL×3, combined organic phase, anhydrous sodium sulfate drying, filtration, reduced pressure concentration, purified by column chromatography, V petroleum ether: ethyl V acetate = 2:1, to give 5-hydroxy-3-methyl-2-(5H)-furone, a yellow solid, yield: 51.97%. |
51.97% | With sulfuric acid In lithium hydroxide monohydrate for 16h; Reflux; | The specific steps are as follows: Weigh methylmalonic acid 10g (84.68mmol) and glyoxal 17.82g (40% aqueous solution, 0.123mol) added to a 250mL round bottom flask, add 100mL of water, magnetic stirring to dissolve, slowly add concentrated H2SO41.12mL under stirring, heat reflux for reaction. TLC [V petroleum ether: ethyl V acetate = 3:2] monitoring reaction, 16h after the end of the reaction, ethyl acetate extraction of 30mL×3, combined organic phase, anhydrous sodium sulfate drying, filtration, reduced pressure concentration, purification by column chromatography, V petroleum ether: ethyl V acetate = 2:1, to give 5-hydroxy-3-methyl-2-(5H)-furone, a yellow solid, Yield: 51.97%. |
51.97% | With sulfuric acid In lithium hydroxide monohydrate for 16h; Reflux; | Weigh 10g (84.68mmol) of methylmalonic acid and 17.82g (40% aqueous solution, 0.123mol) of glyoxal to a 250mL round-bottom flask, add 100mL of water, magnetically stir to dissolve it, slowly add concentratedH2SO41.12mL (0.021mmol) under stirring, and heat reflux for reaction. TLC [Vpetroleum ether:ethyl V acetate= 3:2] monitoring reaction, after 16h the reaction ended, ethyl acetate extracted 30mL×3, combined organic phase, anhydrous sodium sulfate dried, filtered, concentrated under reduced pressure, purified by column chromatography, Vpetroleum ether:ethyl V acetate= 2:1, to give 5-hydroxy-3-methyl-2-(5H)-furone, a yellow solid, Yield: 51.97%. |
30% | With glacial acetic acid In tetrahydrofuran; lithium hydroxide monohydrate at 120℃; for 26h; Inert atmosphere; | |
With hydrogenchloride In lithium hydroxide monohydrate for 16h; Reflux; | 1.02 S02,Synthesis of 3-methyl-5-hydroxyfuran-2(5H)-one At room temperature, add water and glyoxal aqueous solution in a round bottom flask, and then add methylmalonic acid and 6mol/L HCl solution in sequence,Heat to reflux and react for 16h to obtain crude 3-methyl-5-hydroxyfuran-2(5H)-one.Add NaCl solid to the crude product of 3-methyl-5-hydroxyfuran-2(5H)-one obtained above to a saturated state,The organic phase is obtained after extraction with ethyl acetate, and the organic phase is dried over anhydrous sodium sulfate and then revolved to dryness to obtain a solid powder.After the solid powder is reconstituted with a mixture of petroleum ether and ethyl acetate with a volume ratio of 5:2,After column chromatography, a yellow solid is obtained, that is, 3-methyl-5-hydroxyfuran-2(5H)-one. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
7% | Production Example 10 Synthesis of 4-methyl-5-oxo-2,5-dihydrofuran-2-yl 2-(3,4-dimethylphenyl)ethylcarbamate (Compound No. 10) Under argon atmosphere, 5-hydroxy-3-methylbutenolide (0.06 g, 0.53 mmol) was dissolved in dichloromethane (1 ml), and thereto was added N,N-diethylaniline (0.10 ml, 0.62 mmol), followed by triphosgene (0.05 g, 1.8 mmol). Then, the mixture was reacted for 2 hours. To the reaction mixture was added <strong>[17283-14-6]2-(3,4-dimethylphenyl)ethylamine</strong> (0.08 g, 0.53 mmol), and then the mixture was stirred overnight. The reaction solution was quenched with 1M hydrochloric acid, and then extracted with dichloromethane. The resulting organic layer was washed with saturated sodium chloride solution, dried over anhydrous magnesium sulfate, concentrated, and then purified by a column chromatography to give the target compound (0.011 g, yield 7%). White solid, m. p. 103-105C 1H-NMR (300 MHz, CDCl3) delta 1.96(br s, 3H), 2.23(s, 3H), 2.24(s, 3H), 2.77(t, J = 6.9Hz, 2H), 3.43-3.51(m, 2H), 4.82 (bar s, 1H), 6.84-7.08(m, 5H) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
0.98 g | With triethylamine In di-isopropyl ether at 20℃; | 2 Synthesis of 4-methyl-5-oxo-2,5-dihydrofuran-2-yl benzylcarbamate (Compound No. 2) Production Example 2 Synthesis of 4-methyl-5-oxo-2,5-dihydrofuran-2-yl benzylcarbamate (Compound No. 2) Into diisopropyl ether (10 ml) was dissolved 3-methyl-5-hydroxybutenolide (1.14 g, 10.0 mmol), and thereto were added triethylamine (3 drops) and benzyl isocyanate (1.33 g, 10.0 mmol). Then, the mixture was stirred at room temperature overnight. After the completion of the reaction, the reaction solution was quenched with saturated ammonium chloride solution, extracted with ethyl acetate, and washed with saturated sodium chloride solution. The resulting organic layer was dried over magnesium sulfate, and purified by a column chromatography to give the target compound (0.98 g). Crystalline solid, m.p 72-75°C 1H NMR(CDCl3): δ = 1.93-1.97(m, 3H), 4.40-4.42(m, 2H), 5.23(br s, 1H) , 6.86-6.90(m, 1H) , 7.26-7.38(m, 6H) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
0.34 g | With triethylamine In di-isopropyl ether at 20℃; | 3 Synthesis of 4-methyl-5-oxo-2,5-dihydrofuran-2-yl phenethylcarbamate (Compound No. 3) Production Example 3 Synthesis of 4-methyl-5-oxo-2,5-dihydrofuran-2-yl phenethylcarbamate (Compound No. 3) In diisopropyl ether (5 ml) was dissolved 3-methyl-5-hydroxybutenolide (0.44 g, 3.83 mmol), and thereto were added triethylamine (3 drops) and phenethylisocyanate (0.56 g, 3.83 mmol). Then, the mixture was stirred at room temperature overnight. After the completion of the reaction, the reaction solution was quenched with saturated ammonium chloride solution, extracted with ethyl acetate, and washed with saturated sodium chloride solution. The resulting organic layer was dried over magnesium sulfate, and purified by a column chromatography to give the target compound (0.34 g). Crystalline solid, m.p 64-66°C 1H NMR(CDCl3): δ = 1.92(s, 3H), 2.82-2.87(m, 2H), 3.42-3.56(m, 2H), 4.85(br s, 1H), 6.83-6.87(m, 1H), 7.18-7.34(m, 6H) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
0.23 g | Stage #1: 5-Hydroxy-3-methyl-5H-furan-2-one With N,N-diethylaniline In dichloromethane for 0.166667h; Stage #2: bis(trichloromethyl) carbonate In dichloromethane for 2h; Stage #3: N-methylaniline In dichloromethane | 4 Synthesis of 4-methyl-5-oxo-2,5-dihydrofuran-2-yl methyl(phenyl)carbamate (Compound No. 4) Production Example 4 Synthesis of 4-methyl-5-oxo-2,5-dihydrofuran-2-yl methyl(phenyl)carbamate (Compound No. 4) In dry dichloromethane (5 ml), 3-methyl-5-hydroxybutenolide (0.52 g, 4.53 mmol) was stirred, and thereto was added N,N-diethylaniline (0.68 g, 4.53 mmol). Then, the mixture was stirred for 10 minutes. Thereto was added triphosgene (0.450 g, 1.51 mmol), and the mixture was stirred for 2 hours. To this reaction solution was added N-methylaniline (0.430 g, 4.05 mmol), and then the mixture was reacted with stirring overnight. After the completion of the reaction, the reaction solution was quenched with 1M hydrochloric acid, washed with water, extracted with dimethyl ether, and then washed with saturated sodium chloride solution. The resulting organic layer was dried over magnesium sulfate, and purified by a column chromatography to give the target compound (0.23 g). Crystalline solid, m.p 69-71°C 1H NMR(CDCl3): δ = 1.93(s, 3H), 3.32(s, 3H), 6.92(s, 1H), 7.22-7.38(m, 6H) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
0.29 g | Stage #1: 5-Hydroxy-3-methyl-5H-furan-2-one; bis(trichloromethyl) carbonate With N,N-diethylaniline In dichloromethane for 2.5h; Inert atmosphere; Stage #2: benzyl-methyl-amine In dichloromethane for 48h; Inert atmosphere; | 5 Synthesis of 4-methyl-5-oxo-2,5-dihydrofuran-2-yl benzyl(methyl)carbamate (Compound No. 5) Production Example 5 Synthesis of 4-methyl-5-oxo-2,5-dihydrofuran-2-yl benzyl(methyl)carbamate (Compound No. 5) Under argon atmosphere, 3-methyl-5-hydroxybutenolide (0.52 g, 4.53 mmol) was dissolved in dichloromethane (5 ml), and thereto was added N,N-diethylaniline (0.73 ml, 4.53 mmol), followed by triphosgene (0.45 g, 1.51 mmol). Then, the mixture was reacted for 2.5 hours. To the reaction solution was added N-benzylmethylamine (0.58 ml, 4.53 mmol), and the mixture was stirred for 2 days. After the completion of the reaction, the reaction solution was quenched with 1M hydrochloric acid, extracted with ethyl acetate, and washed with saturated sodium chloride solution. The resulting organic layer was dried over magnesium sulfate, and purified by a column chromatography to give the target compound (0.29 g). Oily substance 1H NMR(CDCl3): δ = 1.95-1.99(m, 3H), 2.83(s, 3H), 4.39-4.56(m, 2H), 6.88-6.96(m, 1H), 7.17-7.45(m, 6H) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
0.20 g | Stage #1: 5-Hydroxy-3-methyl-5H-furan-2-one; bis(trichloromethyl) carbonate With N,N-diethylaniline In dichloromethane for 2h; Inert atmosphere; Stage #2: N-Methyl-N-phenethylamine In dichloromethane for 48h; Inert atmosphere; | 6 Synthesis of 4-methyl-5-oxo-2,5-dihydrofuran-2-yl 2-phenethyl(methyl)carbamate (Compound No. 6) Production Example 6 Synthesis of 4-methyl-5-oxo-2,5-dihydrofuran-2-yl 2-phenethyl(methyl)carbamate (Compound No. 6) Under argon atmosphere, 3-methyl-5-hydroxybutenolide (0.52 g, 4.53 mmol) was dissolved in dichloromethane (5 ml), and thereto was added N,N-diethylaniline (0.73 ml, 4.53 mmol), followed by triphosgene (0.45 g, 1.51 mmol). Then, the mixture was reacted for 2.5 hours. To the reaction solution was added N-(2-phenethyl)methylamine (0.62 ml, 4.53 mmol), and then the mixture was stirred for 2 days. After the completion of the reaction, the reaction solution was quenched with 1M hydrochloric acid, extracted with ethyl acetate, and washed with saturated sodium chloride solution. The resulting organic layer was dried over magnesium sulfate, and purified by a column chromatography to give the target compound (0.20 g). Oily substance 1H NMR(CDCl3): δ = 1.95-1.99(m, 3H), 2.90-3.00(m, 2H), 3.03(s, 3H), 3.60-3.75(m, 2H), 7.17-7.45(m, 6H), 7.52(s, 1H) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
14% | Stage #1: 5-Hydroxy-3-methyl-5H-furan-2-one; bis(trichloromethyl) carbonate With N,N-diethylaniline In dichloromethane for 2h; Inert atmosphere; Stage #2: 2-(2,3-dimethylphenyl)ethan-1-amine In dichloromethane | 9 Synthesis of 4-methyl-5-oxo-2,5-dihydrofuran-2-yl 2-(2,3-dimethylphenyl)ethylcarbamate (Compound No. 9) Production Example 9 Synthesis of 4-methyl-5-oxo-2,5-dihydrofuran-2-yl 2-(2,3-dimethylphenyl)ethylcarbamate (Compound No. 9) Under argon atmosphere, 5-hydroxy-3-methylbutenolide (0.29 g, 2.55 mmol) was dissolved in dichloromethane (3.5 ml), and thereto was added N,N-diethylaniline (0.55 ml, 3.4 mmol), followed by triphosgene (0.30 g, 1.0 mmol). Then, the mixture was reacted for 2 hours. To the reaction mixture was added 2-(2,3-dimethylphenyl)ethylamine (0.38 g, 2.55 mmol), and then the mixture was stirred overnight. The reaction solution was quenched with 1M hydrochloric acid, and then extracted with dichloromethane. The resulting organic layer was washed with saturated sodium chloride solution, dried over potassium carbonate, concentrated, and then purified by a column chromatography to give the target compound (0.10 g, yield 14%). White solid, m. p.100-102°C 1H-NMR (300 MHz, CDCl3) δ 1.96-1.97(br s, 3H), 2.23(s, 3H), 2.29(s, 3H), 2.89(t, J = 6.9 Hz, 2H), 3.37-3.49(m, 2H), 4.86(br s, 1H), 6.83-7.06(m, 5H) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
68% | With triethylamine In di-isopropyl ether | 11 Synthesis of 4-methyl-5-oxo-2,5-dihydrofuran-2-yl 2-(3,4-methylenedioxyphenyl)ethylcarbamate (Compound No. 11) Production Example 11 Synthesis of 4-methyl-5-oxo-2,5-dihydrofuran-2-yl 2-(3,4-methylenedioxyphenyl)ethylcarbamate (Compound No. 11) Under argon atmosphere, 5-hydroxy-3-methylbutenolide (0.10 g, 0.876 mmol) was dissoled in diisopropyl ether (5 m), and thereto was added triethylamine (0.13 ml, 0.94 mmol), followed by 2-(3,4-methylenedioxyphenyl)ethylisocyanate (0.167 g, 0.876 mmol). Then, the mixture was stirred overnight. The reaction solution was quenched with 1M hydrochloric acid, and then extracted with ethyl acetate. The resulting organic layer was washed with saturated sodium chloride solution, dried over anhydrous magnesium sulfate, concentrated, and then purified by a column chromatography to give the target compound (0.182 g, yield 68%). White solid, m. p. 127-129°C 1H-NMR (300 MHz, CDCl3) 5 1.97(br s, 3H), 2.76(t, J = 6.9Hz, 2H), 3.40-3.48 (m, 2H), 4.82(br s, 1H), 5.94(s, 2H), 6.81-6.87(m, 5H) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
0.05 g | With triethylamine In di-isopropyl ether | 1 Synthesis of 4-methyl-5-oxo-2,5-dihydrofuran-2-yl phenylcarbamate (Compound No. 1) Production Example 1 Synthesis of 4-methyl-5-oxo-2,5-dihydrofuran-2-yl phenylcarbamate (Compound No. 1) In diisopropyl ether (10 ml), 3-methyl-5-hydroxybutenolide (0.800 g, 7.01 mmol) was stirred, and thereto was added with stirring triethylamine (5 to 6 drops), followed by phenyl isocyanate (0.700 g, 5.85 mmol). Then, the mixture was stirred overnight. After the completion of the reaction, the reaction solution was quenched with 1M hydrochloric acid, extracted with diethyl ether, and washed with saturated sodium chloride solution. The resulting organic layer was dried over magnesium sulfate, purified by a column chromatography to give the target compound (0.05 g). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
65% | Stage #1: ethyl 4-acetoxy-4-chloro-2-hydroxy-2-methylbutanoate With hydrogenchloride; acetic acid In ethanol for 4h; Reflux; Stage #2: With water In ethanol for 0.75h; Reflux; | 8 Hydrolysis and cyclization [0425j A 1000 mL round bottom flask containing the crude aldol product (30.55 g, 128 mmol) was equipped with an oversized stirbar and taken up in absolute ethanol (345 mL) to give a yellow solution. To the stirred solution was added glacial acetic acid (17 mL) and concentrated HC1 (17 mL). A refiux condenser was fitted to the flask and the solution heated to reflux for 4 hours. At this time, deionized water (430 mL) was added and the ethanol removed by fractional distillation until distillation rate slows and internal temperature rises to approximately 90°C and volume of distillate is approximately 135% of initially added ethanol. The condenser was returned to reflux set up and the deep golden reaction mixture heated at reflux for 45 minutes. The cooled reaction mixture was extracted with ethyl acetate (3x 150 mL). Combined extracts were washed with brine (lx 100 mL) and dried Na2SO4. Filtered to give a golden solution, concentrated to give an orange oil (15.19 g). The crude orange oil was subjected to bulb-to-bulb distillation, collecting material at 120-135°C/8 mbar. The pale yellow oil (9.47 g, 65%) slowly solidified on standing. |
14.6 g | With hydrogenchloride; acetic acid In ethanol for 4h; Reflux; | 1.2 Step 2: Preparation of Intermediate 5 (5-hydroxy-3-methylfuran-2(5H)-one) 12 N HC1 (34 mL) and HOAc (34 mL) were added to the solution of crude product 4 in 700 mL of 200 proof ethanol to give a golden solution. The reaction was refluxed for 4 hours and 860 mL water was added. 960 mL solvent was removed under reduced pressure and the reaction mixture was refluxed for one hour. The cooled reaction was extracted with ethyl acetate (6x200 mL) until no product was observed in the aqueous layer via thin layer chromatography (TLC). The combined ethyl acetate was washed with brine (100 mL), dried over MgSCL, filtered and condensed. The residue was loaded on silica gel and eluted with 1 : 1 heptane: EA to give 15.0 g yellow solid which was slurried in 60 mL heptane for 20 min to give the product as a yellow solid. The solid was slurried in 60 mL heptane, filtered to give the product as a pale yellow solid (14.6 g). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
53% | With thionyl chloride In dichloromethane; N,N-dimethyl-formamide for 2h; Reflux; | 8 Chlorination (FIG. 1OC) A 25 mL 19j rbf was capped with a take-off head (2 necked, 2 x 19j), capped with a 19j glass stopper and 19j reflux condenser. The flask was charged with CH2C12 (5 mL), 50C12 (1 mL, 14 mmol, 1.4 equiv) and a drop of DMF, then heated to reflux. A golden solution of hydroxybutenolide (1.15 g, 10 mmol) in CH2C12 (5 mL) was added dropwise to the refluxing vapours at such a rate to maintain reflux with immediate gas evolution. After two hours of reflux, the reaction mixture was cooled to rt, diluted with CH2C12 (20 mL) and poured into saturated NaHCO3 (50 mL) containing ice and rapidly stirred to destroy excess 50C12. When gas evolution has ceased the CH2C12 layer was separated and the aqueous extracted with CH2C12 (2 x 20 mL). Combined CH2C12 extracts were washed with brine (1 x 50 mL) and dried with freshly pulverized Mg504. The clear orange solution was filtered and concentrated to give a thin red liquid (1.106 g). The crude liquid was subjected to bulb-to-bulb distillation, collecting a clear colourless distillate (0.73 g, 53%) at 120-122°C/S mbar. |
53% | With thionyl chloride; N,N-dimethyl-formamide In dichloromethane for 2h; Reflux; | [00353] A 25 mL 19j rbf was capped with a take-off head (2 necked, 2 x 19j), capped with a 19 j glass stopper and 19j reflux condenser. The flask was charged with CH2C12 (5 mL), SOCl2 (1 mL, 14 mmol, 1.4 equiv) and a drop of DMF, then heated to reflux. A golden solution of hydroxybutenolide (1.15 g, 10 mmol) in CH2C12 (5 mL) was added dropwise to the refluxing vapours at such a rate to maintain reflux with immediate gas evolution. After two hours of reflux, the reaction mixture was cooled to rt, diluted with CH2C12 (20 mL) and poured into saturated NaHC03 (-50 mL) containing ice and rapidly stirred to destroy excess SOCl2. When gas evolution has ceased the CH2C12 layer was separated and the aqueous extracted with CH2C12 (2 x 20 mL). Combined CH2C12 extracts were washed with brine (1 x 50 mL) and dried with freshly pulverized MgS04. The clear orange solution was filtered and concentrated to give a thin red liquid (1.106 g). The crude liquid was subjected to bulb-to-bulb distillation, collecting a clear colourless distillate (0.73 g, 53%) at 120-122°C/5 mbar. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
58% | With carbon tetrabromide; triphenylphosphine In dichloromethane at 0 - 20℃; for 2.5h; | |
58% | With carbon tetrabromide; triphenylphosphine In dichloromethane at 0 - 20℃; for 2.5h; | 1 The intermediate (1 eq) obtained in the previous step was dissolved in 20 mL of anhydrous dichloromethane, and the reaction system was placed at 0 °C, and carbon tetrabromide (1.4 eq) and triphenylphosphine ( 1.4 eq), then the system was gradually returned to room temperature and stirred for 2.5 h. After the reaction, the reaction system was spin-dried, and the column chromatography separation and purification (PE: EA=6:1-3:1, v/v) obtained the yellow oily liquid and was the product D ring, and the yield was 58%. |
56.07% | With carbon tetrabromide; triphenylphosphine In dichloromethane at 20℃; for 2.5h; | Weigh 5-hydroxy-3-methyl-2-(5H)-furfuranone 5g (43.82mmol) added to the dried three-mouth round bottom flask, under magnetic stirring, added dried dichloromethane 384mL to dissolve it, and slowly added carbon tetrabromide 17.44g (52.58mmol) and triphenylphosphine 14.94g (56.96mmol) at 0 °C, and the reaction system was restored to room temperature after the dropwise was added for reaction. TLC [V petroleum ether: ethyl V acetate = 2:1] monitoring reaction, after 2.5h the reaction ended, concentrated under reduced pressure, purified by column chromatography, V petroleum ether: ethyl V acetate = 3:2, to give 5-bromo-3-methyl-2-(5H)-furanone, a brown liquid, yield: 56.07%. |
56.07% | With carbon tetrabromide; triphenylphosphine In dichloromethane at 0 - 20℃; for 2.5h; | Weigh 5-hydroxy-3-methyl-2-(5H)-furfuranone 5g (43.82mmol) added to the dried three-mouth round bottom flask, under magnetic stirring, added dried dichloromethane 384mL to dissolve it, and slowly added carbon tetrabromide 17.44g (52.58mmol) and triphenylphosphine 14.94g (56.96mmol) at 0 °C, and the reaction system was restored to room temperature after the dropwise was added for reaction. TLC [V petroleum ether: ethyl V acetate = 2:1] monitoring reaction, after 2.5h the reaction ended, concentrated under reduced pressure, purified by column chromatography, V petroleum ether: ethyl V acetate = 3:2, to give 5-bromo-3-methyl-2-(5H)-furanone, a brown liquid, yield: 56.07%. |
56.07% | With carbon tetrabromide; triphenylphosphine In dichloromethane at 0 - 20℃; for 2.5h; | Weigh 5-hydroxy-3-methyl-2-(5H)-furanone 5g (43.82mmol) added to the dried three-mouth round bottom flask, under magnetic stirring, added dried dichloromethane 384mL to dissolve it, and slowly added carbon tetrabromide 17.44g (52.58mmol) and triphenylphosphine 14.94g (56.96mmol) at 0 °C, and the reaction system was restored to room temperature after the dropwise was added for reaction. TLC [V petroleum ether: ethyl V acetate = 2:1] monitoring reaction, after 2.5h the reaction ended, concentrated under reduced pressure, purified by column chromatography, V petroleum ether: ethyl V acetate = 3:2, to give 5-bromo-3-methyl-2-(5H)-furanone, a brown liquid, yield: 56.07%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With pyridine In chloroform | Synthesis of AB12 [00373] AB12 was synthesized from commercially available para-toluenesulfonyl chloride and hydroxybutenolide prepared by methods described above. The sulfonylation of hydroxybutenolide with para-toluenesulfonlyl chloride was achieved using chloroform as solvate with pyridine as base. Purification was achieved by column chromatography and re-crystallization. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
9.47 g | Stage #1: 2-oxo-propionic acid ethyl ester; vinyl acetate With titanium tetrachloride In dichloromethane at 0℃; for 4h; Inert atmosphere; Stage #2: With hydrogenchloride; acetic acid In ethanol; water for 4.75h; Reflux; | [00351] Synthesis of chlorobutenolide: A 1000 mL 3-necked (19j, 34j, 19j) round bottom flask was equipped with an oversized stirbar, nitrogen bubbler (19j), reducing adapter (19j to 34j) topped with a pressure equalizing dropping funnel capped with 19j rubber septa (34j) and rubber septa (19j). The assembled glassware was flushed under nitrogen and flame-dried under nitrogen purge. CH2C12 was charged to the flask (212 mL, anhydrous) and dropping funnel (106 mL). At room temperature, TiCl4 (16.5 mL, 150 mmol) was added to the flask to give a clear, colourless solution. The titanium tetrachloride solution was cooled in an ice water bath and the dropping funnel charged with ethyl pyruvate (16.7 mL, 150 mmol) and vinyl acetate (13.8 mL, 150 mmol). The carbonyl solution in CH2C12 was added dropwise to the titanium tetrachloride solution over two hours, generating a bright yellow-orange suspension. When addition is complete, the suspension was further stirred for two hours at 0°C (ice water bath). The clear orange-red solution was quenched with deionized water (140 mL) (caution: exothermic with vigourous gas production). CH2C12 separated and the aqueous layer extracted with CH2C12 (2x100 mL). Combined CH2C12 extracts were washed with deionized water (1x100 mL), brine (1x100 mL) and dried with Na2S04. Filtered to give a clear golden yellow solution, concentrated to give a bright yellow oil (30.55 g, 85%). The yellow oil darkens on standing and decomposes releasing acrid fumes; these deformulation products complicate downstream purification. Can be stored cold in the refrigerator and can be used directly in the following step without purification. [00352] A 1000 mL round bottom flask containing the crude aldol product (30.55 g, 128 mmol) was equipped with an oversized stirbar and taken up in absolute ethanol (345 mL) to give a yellow solution. To the stirred solution was added glacial acetic acid (17 mL) and concentrated HC1 (17 mL). A reflux condenser was fitted to the flask and the solution heated to reflux for 4 hours. At this time, deionized water (430 mL) was added and the ethanol removed by fractional distillation until distillation rate slows and internal temperature rises to approximately 90°C and volume of distillate is approximately 135% of initially added ethanol. The condenser was returned to reflux set up and the deep golden reaction mixture heated at reflux for 45 minutes. The cooled reaction mixture was extracted with ethyl acetate (3x150 mL). Combined extracts were washed with brine (1x100 mL) and dried Na2S04. Filtered to give a golden solution, concentrated to give an orange oil (15.19 g). The crude orange oil was subjected to bulb-to-bulb distillation, collecting material at 120- 135°C/8 mbar. The pale yellow oil (9.47 g, 65%) slowly solidified on standing. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
16% | With tetra-(n-butyl)ammonium iodide; potassium carbonate In dichloromethane; water-d2 at 20℃; for 96h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
77% | With 4-methyl-morpholine In tetrahydrofuran at 20℃; for 18h; diastereoselective reaction; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1.8 g | With 4-methyl-morpholine In tetrahydrofuran at 0 - 20℃; for 24h; diastereoselective reaction; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
96 mg | With 4-methyl-morpholine In tetrahydrofuran at 0 - 20℃; for 18h; diastereoselective reaction; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
200 mg | With 4-methyl-morpholine In tetrahydrofuran at 0 - 20℃; for 22h; diastereoselective reaction; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
92% | With 4-methyl-morpholine In tetrahydrofuran at 0℃; for 0.25h; diastereoselective reaction; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
7%; 60% | With lithium tri-t-butoxyaluminum hydride; In tetrahydrofuran; at -30 - -15℃; for 3h;Inert atmosphere; | A solution of 5.34 g LiAlH(t-BuO)3 (21.00 mmol) in 40 cm3 anhydrous THF was added dropwise over a 30-min period to a solution of 1.68 g citraconic anhydride (6, 15.00 mmol) in 50 cm3 anhydrous THF under a nitrogen atmosphere at - 30 C. The temperature was maintained at - 15 C for 3 h and then the reaction mixture was warmed to ambient temperature. The reaction was quenched with 50 cm3 1 M HCl, the solution was saturated with NaCl, the crude product was extracted with EtOAc (3 9 50 cm3), and the combined organic fraction was dried over MgSO4. The solvent was removed in vacuo. Purification by column chromatography (SiO2, 20% AcOEt in petroleum ether) afforded 7a (1.023 g,60%) and 7b (116 mg, 7%) as yellow oils. TLC: Rf = 0.16 (for 7a), 0.15 (for 7b) (20% AcOEt in petroleum ether). 7a: 1H NMR (400 MHz, acetone-d6): d = 6.67 (bs, 1H),6.02 (bs, 1H), 5.87 (p, J = 1.5 Hz, 1H), 2.08 (d,J = 1.5 Hz, 3H) ppm; 13C NMR (100 MHz, acetone-d6):d = 171.30 ([C), 166.65 ([C), 118.68 (CH), 100.25(CH), 13.15 (CH3) ppm; MS (EI): m/z (%) = 114.0 ([M?],2), 113.0 (7), 86.0 (61), 85.0 (13), 69.0 (100), 68.0 (82),41.1 (50), 40.1 (65), 39.1 (93). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
20% | In neat (no solvent) at 120℃; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
31% | In neat (no solvent) at 120℃; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
24% | In neat (no solvent) at 120℃; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
28% | In neat (no solvent) at 120℃; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
44% | In neat (no solvent) at 120℃; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
87% | With toluene-4-sulfonic acid In toluene at 80℃; for 15h; | 3-Methyl-5-(phenylthio)furan-2(5H)-one (5) To a stirred solution of 5-hydroxy-3-methylfuran-2(5H)-one (1.14 g, 10 mmol) in toluene (100 mL) was added p-toluenesulfonic acid (PTSA, 50 mg) followed by thiophenol (1.10 g, 10mmol), and the mixture was heated at 80 °C for 15 h. Toluene was removed under reduced pressure. The crude residue was then diluted with EtOAc (50 mL) and washed by water and brine, dried over Na2SO4, and concentrated. Purification by column chromatography gives the product as solid 5 (1.80 g, 87%). 1H NMR (400 MHz, CDCl3): δ = 7.64-7.46 (m, 2 H), 7.40-7.28 (m, 3 H), 6.96 (p, J = 1.6, 1 H), 6.11 (p, J = 1.9, 1 H), 1.83 (t, J =1.8, 3 H). 13C NMR (100 MHz, CDCl3): δ = 172.84, 144.96, 134.12,132.15, 130.20, 129.27, 129.15, 85.86, 10.59. HRMS (ESI-QTOF):m/z calcd for [M + H]+: 207.0474; found: 207.0470. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With 4-methyl-morpholine In tetrahydrofuran at 0 - 20℃; Inert atmosphere; | 1.3 Step 3: Preparation of MBS-127 (3-(4-Methyl-5-oxo-2,5-dihydro-furan-2-yloxy)-acrylic acid methyl ester) Under nitrogen, methyl propionate (1.85 g , 22 mmol, 1 eq) and 4-methyl morpholine (2.2 g, 22 mmol, 1 eq) were added to the solution of compound 5 (5.0g, 44 mmol, 2 eq) in 50 mL dry tetrahydrofuran (THF) at 0 °C. The reaction was stirred at 0 °C for 15 min then stirred at room temperature (RT overnight. The reaction was condensed and 100 ml NH4CI was added, and then extracted with ethyl acetate (3x100 mL). The combined organic was washed with brine (100 mL), dried over MgSCL, filtered, and condensed. The crude product was purified by chromatography using 2: 1 heptane:ethyl acetate (EA) to afford the product as a pale yellow solid, a representative NMR of which is shown in FIG. 8 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
78% | Stage #1: 5-Hydroxy-3-methyl-5H-furan-2-one With potassium carbonate; N-ethyl-N,N-diisopropylamine In acetonitrile at 20℃; for 0.25h; Stage #2: N-(phenyl)bromoacetamide In acetonitrile for 10h; | 1-4 Preparation Example 3 Synthesis of compound 1 Add potassium carbonate (1.2g),N, N-diisopropylethylamine (1.1g), 5-hydroxy-3-methylfuran-2 (5H) -one (0.64g) were added to the reaction flask,Acetonitrile (50 mL) was added with stirring. After 15 minutes of reaction at room temperature, 2-bromo-N-phenylacetamide (1.2 g) was added.The reaction was continued to stir for 10 h. After the reaction was completed.Diatomite assisted suction filtration to remove insoluble matter,The acetonitrile in the solution was removed under reduced pressure, and the obtained residue was subjected to column chromatography to obtain 1.1 g of a colorless oily compound 1.Its yield is 78%, |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
43% | Stage #1: 5-Hydroxy-3-methyl-5H-furan-2-one With potassium carbonate; N-ethyl-N,N-diisopropylamine In acetone at 20℃; for 0.25h; Stage #2: 2-bromo-N-(2,6-dimethyl-phenyl)-acetamide In acetone for 10h; | 5 Preparation Example 5 Synthesis of compound 46 Add potassium carbonate (0.61g), 5-hydroxy-3-methylfuran-2 (5H) -one (0.2g) to the reaction flask,Acetone (50 mL) was added with stirring. After 15 minutes of reaction at room temperature, 2-bromo-N- (2,6-dimethylphenyl) acetamide (0.41 g) was added, and the reaction was continued with stirring for 10 hours. After the reaction was completed. Diatomite-assisted suction filtration was used to remove insoluble matter, and the acetone in the solution was removed under reduced pressure. The obtained residue was subjected to column chromatography to obtain 0.21 g of a colorless oily compound 46 with a yield of 43%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
46% | Stage #1: 5-Hydroxy-3-methyl-5H-furan-2-one With potassium hydrogencarbonate In acetone at 20℃; for 0.25h; Stage #2: 2-bromo-N-(5-indanyl)acetamide In acetone for 10h; | 6 Preparation Example 6Synthesis of compound 63 Add potassium bicarbonate (0.57g), 5-hydroxy-3-methylfuran-2 (5H) -one (0.25g) to the reaction flask,Acetone (50 mL) was added with stirring. After 15 minutes of reaction at room temperature, 2-bromo-N- (5-indanyl) acetamide (0.56 g) was added, and the reaction was continued with stirring for 10 hours. After the reaction was completed. Diatomite assisted suction filtration to remove insoluble matter,The acetone in the solution was removed under reduced pressure, and the obtained residue was subjected to column chromatography to obtain 0.29 g of compound 63 as a white solid.Its yield is 46%, |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
68% | Stage #1: 5-Hydroxy-3-methyl-5H-furan-2-one With potassium carbonate; N-ethyl-N,N-diisopropylamine In acetonitrile at 20℃; for 0.25h; Stage #2: 2-bromo-N-(3-chlorophenyl)acetamide In acetonitrile for 10h; | 12 Preparation Example 12Synthesis of compound 6 This preparation example is prepared by a method similar to that of Preparation Example 11. The molar ratio of the amount of each raw material is the same as that of Preparation Example 11. The difference is that in this preparation example, 2-bromo-N- (3-chlorophenyl) acetamide Replacing 2-bromo-N- (2-chlorophenyl) acetamide in Preparation Example 11 and replacing potassium bicarbonate in Preparation Example 11 with N, N-diisopropylethylamine,The rest are the same as in Preparation Example 11,1.08 g of compound 6 was obtained as a pale yellow oil,Its yield is 68%, |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
49% | Stage #1: 5-Hydroxy-3-methyl-5H-furan-2-one With potassium carbonate; N-ethyl-N,N-diisopropylamine In dichloromethane at 20℃; for 0.25h; Stage #2: 2-bromo-N-(4-chlorophenyl)acetamide In dichloromethane for 10h; | 13 Preparation Example 13Synthesis of compound 7 This preparation example is prepared by a method similar to that of Preparation Example 12. The molar ratio of the amount of each raw material is the same as that of Preparation Example 12, except that 2-bromo-N- (4-chlorophenyl) acetamide is used in this preparation example. The 2-bromo-N- (3-chlorophenyl) acetamide in Preparation Example 12 was replaced, and the acetone in Preparation Example 12 was replaced with dichloromethane. The rest were the same as in Preparation Example 12, and 0.77 g of a white solid was obtained. Compound 7,Its yield is 49%, |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
48% | This preparation example is prepared by a method similar to that of Preparation Example 15. The molar ratio of the amount of each raw material is the same as that of Preparation Example 15. The difference is that 2-bromo-N- (4-trifluoromethyl) ethyl is used in this preparation example. Amide was used to replace 2-bromo-N- (4-iodo) acetamide in Preparation Example 15 and potassium bicarbonate in Preparation Example 15 was replaced with pyridine. The rest were the same as those in Preparation Example 15, and 0.33 g of a white solid compound was obtained. 19,Its yield is 48%, |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
56% | Stage #1: 5-Hydroxy-3-methyl-5H-furan-2-one With dmap; N-ethyl-N,N-diisopropylamine In acetonitrile at 20℃; for 0.25h; Stage #2: α-bromo-(3,4-methylenedioxy)acetophenone In acetonitrile for 10h; | 19 Preparation Example 19Synthesis of compound 66 This preparation example is prepared by a method similar to that of preparation example 18, except that the molar ratio of the amount of each raw material is the same as that of preparation example 18. In this preparation example, N- (3,4-methylenedioxyphenyl) is used. 2-Hydroxyacetamide was used to replace N- (2,4-dichlorophenyl) -2-hydroxyacetamide in Preparation Example 18, and 4-dimethylaminopyridine was used to replace cesium carbonate in Preparation Example 18. As in Preparation Example 18, 0.59 g of a light brown oily compound 66 was obtained in a yield of 56% |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
81% | With triethylamine In dichloromethane; water at 0 - 20℃; for 10h; | 1.4 (4) Add 40 mL of dry fourth solvent (dichloromethane) to the reaction flask containing the intermediate E from which the solvent has been removed under reduced pressure, cool the system to 0°C, and add 2.43 mmol of water dropwise for 1 h while stirring A solution consisting of the raw material F represented by formula (1-7) (the selection of R8 and R9 is shown in compound 52 in Table 1), 5.56 mmol of the second base (Et3N) and 20 mL of the fourth solvent, after dropping Move to room temperature and react for 10h. After the reaction is completed, a second aqueous alkaline inorganic salt solution (saturated NaHCO3 solution) is added to the system for washing to obtain an organic solution containing compound 52 represented by formula (1), and then the organic solution containing compound 52 is concentrated and performed Column chromatography (solvent used: petroleum ether:acetone=20:9) to obtain a white solid, namely compound 52, with a yield of 81%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
87% | Stage #1: bis(trichloromethyl) carbonate; C14H22N2O3S With triethylamine In dichloromethane at 0℃; for 2h; Inert atmosphere; Stage #2: 5-Hydroxy-3-methyl-5H-furan-2-one With dmap; triethylamine In dichloromethane at 0 - 20℃; Inert atmosphere; | 1.2 Step: 2 A solution of triphosgene (0.15 g, 0.50 mmol, 1 equiv.) in dichloromethane (1.9 mL) was cooled to 0°C, and amine (3) (0.15 g, 0.50 mmol, 1 equiv.) and triethylamine (0.2 mL, 1.50 mmol, 3 equiv.) were added thereto, followed by stirring for 2 hours in an argon atmosphere. While the reaction liquid was maintained at 0°C, dichloromethane (5 mL), 5-hydroxy-3-methyl-2-furanone (4a) (0.17 g, 1.5 mmol, 3 equiv.), triethylamine (0.2 mL, 1.50 mmol, 3 equiv.), and N,N-dimethyl-4-aminopyridine (6.1 mg, 0.05 mmol, 10 mol%) were added thereto. The reaction liquid was stirred overnight while its temperature was slowly returned to room temperature. Thereafter, the reaction liquid was quenched with saturated sodium hydrogen carbonate, extracted with dichloromethane (5 mL) (x 3), and dried over anhydrous Na2SO4. After the solvent was evaporated, the residue was purified by silica gel column chromatography (eluate: a mixed solvent of hexane/ethyl acetate), thus yielding a white solid target product (5) (compound 1) (0.19 g, yield: 87%). 1H NMR (600 MHz, CDCl3) δ 7.65 (2H, dt, J = 9.0, 1.8 Hz), 6.99 (2H, dt, J = 9.0, 1.8 Hz), 6.85-6.83 (1H, m), 6.83-6.82 (1H, m), 4.03 (2H, t, J = 6.0 Hz), 3.76 (1H, d, J = 12.0 Hz), 3.65 (1H, d, J = 12.0 Hz), 3.47 (1H, t, J = 10.2 Hz), 3.43 (1H, t, J = 10.2 Hz), 3.19 (1H, br), 3.12 (1H, br), 2.84 (1H, t, J = 10.2 Hz), 2.79 (1H, t, J = 10.2 Hz), 1.97 (3H, s), 1.80 (2H, td, J = 7.2, 6.0 Hz), 1.51 (2H, sextet, J = 7.2 Hz), 0.99 (3H, t, J = 7.2 Hz); 13C NMR (151 MHz, CDCl3) δ 171.1, 163.2, 152.4, 142.1, 134.7, 130.0, 126.4, 115.0, 93.9, 68.4, 45.8, 43.7, 43.4, 31.2, 19.3, 14.0, 10.8, one carbon atom was not found due to overlapping; IR (film) 2940, 2872, 1776, 1717, 1593, 1435, 1346, 1242, 1159, 1092, 1015, 955, 930 cm-1; HRMS (ESI) Calcd for C20H26O7N2NaS+ ([M+Na]+) 461.1353, Found 461.1356. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
82% | Stage #1: bis(trichloromethyl) carbonate; C13H20N2O3S With triethylamine In dichloromethane at 0℃; for 2h; Inert atmosphere; Stage #2: 5-Hydroxy-3-methyl-5H-furan-2-one With dmap; triethylamine In dichloromethane at 0 - 20℃; Inert atmosphere; | 1.3 Step: 3 A solution of triphosgene (18 mg, 0.06 mmol, 1 equiv.) in dichloromethane (0.3 mL) was cooled to 0°C, and amine (3c) (17 mg, 0.06 mmol, 1 equiv.) and triethylamine (25 µL, 0.18 mmol, 3 equiv.) were added thereto, followed by stirring for 2 hours in an argon atmosphere. While the reaction liquid was maintained at 0°C, dichloromethane (0.6 mL), 5-hydroxy-3-methyl-2-furanone (4a) (21 mg, 0.18 mmol, 3 equiv.), triethylamine (25 µL, 0.18 mmol, 3 equiv.), and N,N-dimethyl-4-aminopyridine (0.7 mg, 0.006 mmol, 10 mol%) were added thereto. The reaction liquid was stirred overnight while its temperature was slowly returned to room temperature. The reaction liquid was quenched with saturated sodium hydrogen carbonate, extracted with dichloromethane (3 mL) (× 3), and dried over anhydrous Na2SO4 . After the solvent was evaporated, the residue was purified by silica gel column chromatography (eluate: a mixed solvent of hexane/ethyl acetate), thus yielding a white solid target product (12) (compound 27) (21 mg, yield: 82%). 1H NMR (600 MHz, CDCl3) rotamer A δ 7.73 (2H, d, J = 9.0 Hz), 7.02 (2H, d, J = 9.0 Hz), 6.88 (1H, s), 6.81 (1H, s), 4.68 (1H, d, J = 9.0 Hz), 4.62 (1H, d, J = 9.0 Hz), 4.09-4.01 (2H, m), 3.57 (1H, dt, J = 12.0, 6.0 Hz), 3.53-3.48 (1H, m), 3.32 (1H, dt, J = 9.6, 6.6 Hz), 3.26-3.18 (1H, m), 2.02 (3H, s), 1.84-1.77 (2H, m), 1.51 (2H, sextet, J = 7.8 Hz), 0.99 (3H, t, J = 7.8 Hz); rotamer B δ 7.76 (2H, d, J = 9.0 Hz), 7.00 (2H, d, J = 9.0 Hz), 6.81 (1H, s), 6.79 (1H, s), 4.72 (2H, s), 4.09-4.01 (2H, m), 3.60 (1H, dt, J = 12.0, 6.0 Hz), 3.53-3.48 (1H, m), 3.26-3.18 (2H, m), 1.96 (3H, s), 1.84-1.77 (2H, m), 1.51 (2H, sextet, J = 7.8 Hz), 0.99 (3H, t, J = 7.8 Hz); 13C NMR (151 MHz, CDCl3) mixture of rotamers δ 171.1, 171.0, 163.63, 163.58, 150.9, 150.6, 141.89, 141.86, 134.9, 134.7, 130.0, 129.8, 127.23, 127.18, 115.4, 115.2, 93.5, 68.51, 68.48, 62.5, 61.9, 47.2, 46.4, 44.2, 44.0, 31.1, 19.3, 13.9, 10.8, 10.7; IR (film) 2959, 2874, 1778, 1726, 1593, 1422, 1348, 1260, 1157, 1092, 959 cm-1; HRMS (ESI) Calcd for C19H24O7N2NaS+ ([M+Na]+) 447.1196, Found 447.1191. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With thionyl chloride; triethylamine In N,N-dimethyl-formamide at 100℃; | ||
With thionyl chloride; triethylamine In N,N-dimethyl-formamide Reflux; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With thionyl chloride; triethylamine In N,N-dimethyl-formamide at 100℃; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With thionyl chloride; triethylamine In N,N-dimethyl-formamide Reflux; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
42.7% | With toluene-4-sulfonic acid In toluene at 80℃; for 15h; | 1 Example 1, preparation of compound 11 Weigh 1g5-hydroxy-3-methyl-2-(5H)-furfuranone 1g (8.76mmol) in a 250mL round-bottom flask, add toluene 30m magnetic stirring to dissolve it, add p-toluene sulfonic acid monohydrate 0.045g (0.26mmol), and then add 2,4-dichlorothiophenol 1.57g (8.76mmol), heated reflux at 80 °C for reaction. TLC [Vpetroleum ether:ethyl V acetate= 5:1] detection reaction, the reaction ended after 15 hours. Distillation under reduced pressure, removal of toluene, ethyl acetate extract 10 mL×3, combined organic phase, anhydrous sodium sulfate drying, reduced pressure concentration, column chromatography, Vpetroleum ether: Vethyl acetate= 10:1. Total yield: 42.70%. |
Tags: 931-23-7 synthesis path| 931-23-7 SDS| 931-23-7 COA| 931-23-7 purity| 931-23-7 application| 931-23-7 NMR| 931-23-7 COA| 931-23-7 structure
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Code | Phrase |
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Code | Phrase |
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Response | |
Code | Phrase |
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P378 | |
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P371 + P380 + P375 | In case of major fire and large quantities: Evacuate area. Fight fire remotely due to the risk of explosion. |
Storage | |
Code | Phrase |
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Disposal | |
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Physical hazards | |
Code | Phrase |
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H260 | In contact with water releases flammable gases which may ignite spontaneously |
H261 | In contact with water releases flammable gas |
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Health hazards | |
Code | Phrase |
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H311 | Toxic in contact with skin |
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H316 | Causes mild skin irritation |
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H318 | Causes serious eye damage |
H319 | Causes serious eye irritation |
H320 | Causes eye irritation |
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H362 | May cause harm to breast-fed children |
H370 | Causes damage to organs |
H371 | May cause damage to organs |
H372 | Causes damage to organs through prolonged or repeated exposure |
H373 | May cause damage to organs through prolonged or repeated exposure |
Environmental hazards | |
Code | Phrase |
H400 | Very toxic to aquatic life |
H401 | Toxic to aquatic life |
H402 | Harmful to aquatic life |
H410 | Very toxic to aquatic life with long-lasting effects |
H411 | Toxic to aquatic life with long-lasting effects |
H412 | Harmful to aquatic life with long-lasting effects |
H413 | May cause long-lasting harmful effects to aquatic life |
H420 | Harms public health and the environment by destroying ozone in the upper atmosphere |
Sorry,this product has been discontinued.
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