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CAS No. : | 7686-78-4 | MDL No. : | MFCD00196937 |
Formula : | C11H16O4 | Boiling Point : | - |
Linear Structure Formula : | - | InChI Key : | UOQTXZICFVMERR-UHFFFAOYSA-N |
M.W : | 212.24 | Pubchem ID : | 111025 |
Synonyms : |
|
Num. heavy atoms : | 15 |
Num. arom. heavy atoms : | 0 |
Fraction Csp3 : | 0.64 |
Num. rotatable bonds : | 7 |
Num. H-bond acceptors : | 4.0 |
Num. H-bond donors : | 0.0 |
Molar Refractivity : | 54.71 |
TPSA : | 52.6 Ų |
GI absorption : | High |
BBB permeant : | Yes |
P-gp substrate : | No |
CYP1A2 inhibitor : | Yes |
CYP2C19 inhibitor : | No |
CYP2C9 inhibitor : | No |
CYP2D6 inhibitor : | No |
CYP3A4 inhibitor : | No |
Log Kp (skin permeation) : | -6.35 cm/s |
Log Po/w (iLOGP) : | 2.91 |
Log Po/w (XLOGP3) : | 1.76 |
Log Po/w (WLOGP) : | 1.3 |
Log Po/w (MLOGP) : | 1.36 |
Log Po/w (SILICOS-IT) : | 2.07 |
Consensus Log Po/w : | 1.88 |
Lipinski : | 0.0 |
Ghose : | None |
Veber : | 0.0 |
Egan : | 0.0 |
Muegge : | 0.0 |
Bioavailability Score : | 0.55 |
Log S (ESOL) : | -1.8 |
Solubility : | 3.34 mg/ml ; 0.0158 mol/l |
Class : | Very soluble |
Log S (Ali) : | -2.48 |
Solubility : | 0.699 mg/ml ; 0.00329 mol/l |
Class : | Soluble |
Log S (SILICOS-IT) : | -1.88 |
Solubility : | 2.77 mg/ml ; 0.0131 mol/l |
Class : | Soluble |
PAINS : | 0.0 alert |
Brenk : | 3.0 alert |
Leadlikeness : | 1.0 |
Synthetic accessibility : | 2.9 |
Signal Word: | Warning | Class: | N/A |
Precautionary Statements: | P280-P305+P351+P338 | UN#: | N/A |
Hazard Statements: | H302 | Packing Group: | N/A |
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 |
---|---|---|
88% | Stage #1: diethyl malonate With sodium hydride In tetrahydrofuran at 0℃; for 1h; Inert atmosphere; Stage #2: (E)-1,4-dibromobutene In tetrahydrofuran at 0 - 70℃; Inert atmosphere; | |
87% | Stage #1: diethyl malonate With sodium hydride In tetrahydrofuran; mineral oil at 0℃; for 1h; Inert atmosphere; Stage #2: (E)-1,4-dibromobutene In tetrahydrofuran; mineral oil at 0 - 20℃; Inert atmosphere; | |
87% | With caesium carbonate In tetrahydrofuran at 60℃; for 16h; Inert atmosphere; |
86% | Stage #1: diethyl malonate With sodium hydride In tetrahydrofuran at 0℃; for 2h; Inert atmosphere; Stage #2: (E)-1,4-dibromobutene In tetrahydrofuran at 0 - 20℃; Inert atmosphere; | |
70% | With sodium hydride In hexane; dimethyl sulfoxide for 8h; Ambient temperature; | |
63% | With potassium carbonate In ethanol for 12h; Heating; | |
53% | With sodium hydride In tetrahydrofuran; mineral oil at 0 - 20℃; for 16h; Schlenk technique; Inert atmosphere; | |
22% | Stage #1: diethyl malonate With sodium ethanolate In ethanol at 20℃; for 1h; Stage #2: (E)-1,4-dibromobutene In ethanol for 24h; Heating; | |
Stage #1: diethyl malonate With sodium ethanolate Stage #2: (E)-1,4-dibromobutene | ||
Stage #1: diethyl malonate With sodium ethanolate In ethanol; toluene at 20℃; for 0.5h; Stage #2: (E)-1,4-dibromobutene In ethanol; toluene at 20℃; for 22h; Stage #3: With sodium hydroxide In ethanol; water; toluene for 1h; | 8 [Example 8] Production of 1,1-di-ethoxycarbonyl-2-vinylcyclopropane [Example 8] Production of 1,1-di-ethoxycarbonyl-2-vinylcyclopropane 35.4 g (221 mmol) of diethyl malonate and 402 mL of toluene were added into a three-necked flask (1 L), and thereafter, 82.7 mL (211 mmol) of a 20% sodium ethoxide ethanol solution was added thereto as a base. The obtained mixture was stirred at room temperature for 0.5 hours, and 21.5 g of trans-1,4-dibromo-2-butene (101 mmol; a reagent manufactured by Sigma-Aldrich) was then added to the reaction solution. The obtained mixture was stirred at room temperature for 22 hours, and 241 mL of a 1 M sodium hydroxide aqueous solution was then added to the reaction solution. The mixture was stirred for 1 hour, and an organic layer was then separated. A water layer was re-extracted with 240 mL of toluene, and organic layers were then gathered. The gathered organic layer was washed with 240 mL of water three times. The resultant was filtrated, while washing the residue with toluene. The obtained filtrate was concentrated at 45°C under reduced pressure, so as to obtain 23.6 g of 1,1-di-ethoxycarbonyl-2-vinylcyclopropane in the form of a crude product of a light yellow oily substance. This crude product contained 21.2 g of 1,1-di-ethoxycarbonyl-2-vinylcyclopropane (yield: 99%). | |
In tetrahydrofuran |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95% | With lithium aluminium tetrahydride In tetrahydrofuran at 0℃; for 2h; Inert atmosphere; Heating; | |
93% | With lithium aluminium tetrahydride In tetrahydrofuran for 2h; Heating; | |
84% | With lithium aluminium tetrahydride In diethyl ether for 3h; Heating; |
84% | With lithium aluminium tetrahydride | |
57% | With lithium aluminium tetrahydride In diethyl ether at 38℃; for 24h; Inert atmosphere; | |
With lithium aluminium tetrahydride In tetrahydrofuran for 0.5h; Ambient temperature; | ||
With lithium aluminium tetrahydride In tetrahydrofuran at 0 - 60℃; for 2h; | (2-Vinylcyclopropane-1,1-diyl)dimethanol (S1) A solution of diester 1c (14 mmol) in THF (50 mL) was cooled to 0°C and LiAlH4 (4 equiv.) was added in several portions. After heating for 2h at 60°C, the mixture was cooled to room temperature, 2mL H2O followed by 1M solution of Rochelle's salt (10 mL) were cautiously added and the layers separated out. The solid residue was filtered and the filtrate was concentrated, then extract with 3×50mL DCM. The combined organic layers were dried over Na2SO4. After evaporation of solvent, di-alcohol S1 appeared as colorless liquid, which was used further without purification (1.7g, crude yield 95%); 1H NMR (400MHz, CDCl3) δ 5.67 (ddd, J= 17.02, 10.14, 8.09Hz, 1H), 5.15 (dd, J= 17.02, 0.85Hz, 1H), 5.04 (dd, J= 10.14, 0.85Hz, 1H), 3.83 (dd, J= 11.71, 6.52Hz, 1H), 3.63-3.57 (m, 3H), 3.30 (br s, 2H), 1.63-1.51 (m, 1H), 0.83 (dd, J 8.09, 5.43Hz, 1H), 0.65 (t, J 5.43Hz, 1H). 13C NMR (101MHz, CDCl3): δ 136.2, 115.9, 69.1, 64.4, 30.5, 25.2, 15.5. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
99.5% | With sodium methoxide In ethanol; n-heptane at 55 - 60℃; | 1-10 1) reaction step: add sodium ethoxide ethanol solution (formed by 16.32Kg sodium ethoxide, 32Kg ethanol and 33.28Kg heptane) in the enamel reaction kettle, open stirring, be warming up to 55 ; Weigh diethyl malonate 40.3 Kg is added dropwise in the above-mentioned enamel reaction kettle;Weigh the trans-1,4-dichloro-2-butene of 30Kg, add it dropwise to the above-mentioned enamel reaction kettle, and finish the dropwise addition in 1.52 hours; and 33.28kg heptane), added to the above-mentioned enamel reaction kettle, and the temperature was raised to 60 ° C after dropping in 1 to 1.5 hours, and reacted for 4.5 h, and now the reaction solvent was composed of ethanol and heptane in a mass ratio of 49:51;2) After-treatment: the reaction is finished, the heating is stopped, and the temperature is lowered to 20° C.; after filtration, the mother liquor is transferred to the enamel reaction kettle, and after adding 70g of hydroquinone, decompression is carried out at 60° C., and the vacuum degree is not less than 0.07Mpa. Concentrated to give an oil,That is 2-vinylcyclopropane-1,1-diethyldicarboxylate. The yield was 99.5%, the solvent residue in the obtained 2-vinylcyclopropane-1,1-diethyldicarboxylate was 0.04%, and no raw material trans-1,4-dichloro-2-butene remained, The distillate ethanol and heptane can be directly recovered as the mixed solvent of ethanol and heptane used as the starting sodium ethoxide solution, so there is no waste water discharge. |
78% | With potassium etoxide In ethanol | |
In ethanol; lithium hydroxide monohydrate | 2 1,1-Bis-ethoxycarbonyl-2-vinylcyclopropane EXAMPLE 2 1,1-Bis-ethoxycarbonyl-2-vinylcyclopropane To a solution of 18.4 g (2 equivalents) in 300 ml of anhydrous ethanol is added rapidly 164 g (1 equivalent) of diethyl malonate. 1,4-Dichloro-2-butene (98% mixture of cis and trans, Aldrich) (50 g, 1 equivalent) is slowly added to the warm, stirred suspension of the diethyl sodio malonate during 15 minutes after which the mixture is refluxed for 3 hours. Upon cooling, the mixture is poured into 1.2 liters of water and an oil isolated by ether extraction. The ether extract is dried over magnesium sulfate and distilled to give 1,1-bis-ethoxy-carbonyl-2-vinylcyclopropane, B.P. 108°-116° C./14 mm. |
Stage #1: diethyl propanedioate With potassium etoxide In ethanol; toluene at 20℃; for 0.5h; Stage #2: trans-1,4-dichlorobut-2-ene In ethanol; toluene at 20℃; for 120h; Stage #3: With sodium hydroxide In ethanol; lithium hydroxide monohydrate; toluene for 1h; | 9 [Example 9] Production of 1,1-di-ethoxycarbonyl-2-vinylcyclopropane [Example 9] Production of 1,1-di-ethoxycarbonyl-2-vinylcyclopropane 35.2 g (220 mmol) of malonic acid diethyl esterdiethyl malonate and 400 mL of toluene were added into a three-necked flask (1 L), and thereafter, 82.3 mL (210 mmol) of a 20% sodium ethoxide ethanol solution was added thereto as a base. The obtained mixture was stirred at room temperature for 0.5 hours, and 12.5 g of trans-1,4-dichloro-2-butene (100 mmol; a reagent manufactured by Tokyo Chemical Industry Co., Ltd.) was then added to the reaction solution. The obtained mixture was stirred at room temperature for 5 days, and 240 mL of a 1 M sodium hydroxide aqueous solution was then added to the reaction solution. The mixture was stirred for 1 hour, and an organic layer was then separated. A water layer was re-extracted with 200 mL of toluene, and organic layers were then gathered. The gathered organic layer was washed with 200 mL of water three times, and the resultant was then filtrated, while washing the residue with toluene. The obtained filtrate was concentrated at 45°C under reduced pressure, so as to obtain 24.4 g of 1,1-di-ethoxycarbonyl-2-vinylcyclopropane in the form of a crude product of a light yellow oily substance. This crude product contained 19.5 g of 1,1-di-ethoxycarbonyl-2-vinylcyclopropane (yield: 92%). | |
1.25 kg | With potassium etoxide; hydroquinone In ethanol Reflux; Large scale; | 1; 2 Example 1 Add 5L of 20% sodium ethoxide ethanol solution to the enamel reaction kettle, start stirring, and raise the temperature to 55 ;Weigh 1kg of diethyl malonate and drop it into the above enamel reactor, add 0.4kg of hydroquinone;Weigh trans-1,4-dichloro-2-butene, the molar ratio of trans-1,4-dichloro-2-butene to diethyl malonate is 1: 1, and add dropwise to the above enamel In the reaction kettle, the dropwise addition is completed within 1.5 to 2 hours;Weigh 1L of 20% sodium ethoxide ethanol solution, dropwise add it to the above enamel reaction kettle, and dropwise add it within 1 to 1.5 hours;Raise the temperature to reflux and react for 3h; after the reaction is over, stop heating and cool down; quench with water;Extract twice with methyl tert-butyl ether 3 times the volume of trans-1,4-dichloro-2-butene and combine the organic layers; then use the same amount of sodium chloride as methyl tert-butyl ether Wash 2 times;Separate the liquid and add hydroquinone with a mass of 5 ‰ of trans-1,4-dichloro-2-butene in the organic layer.Concentrate under reduced pressure; 1.25 kg of intermediate 1 (AX-1) was obtained. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
73% | With ytterbium(III) triflate In dichloromethane at 20℃; for 42h; | |
73% | With ytterbium(III) triflate In dichloromethane at 20℃; for 42h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90% | With potassium hydroxide In ethanol at 20℃; for 12h; | |
90% | Stage #1: diethyl 2-vinylcyclopropane-1,1-dicarboxylate With potassium hydroxide In ethanol at 20℃; for 12h; Stage #2: With hydrogenchloride | |
With potassium hydroxide Optical yield = 80 %de; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95% | With 2,2'-azobis(isobutyronitrile) In chlorobenzene at 65℃; for 15h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
91% | With tris-(dibenzylideneacetone)dipalladium(0); caesium carbonate In tetrahydrofuran; water at 40℃; for 5h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
70.4% | 34 EXAMPLE 34 Following the procedure described in Example 7, except that 50% less methylene chloride was used, trans 1,4-dichlorobutene-2 and diethyl malonate were reacted in the presence of potassium hydroxide and tricaprylylmethylammonium chloride. After workup, the crude reaction product was distilled and 596.7 g distillate (pure diethyl 2-vinylcyclopropane-1,1-dicarboxylate; 70.4% yield) and 78 g distillation residue obtained. A second reaction was carried out in an identical manner except that the tricaprylylmethylammonium chloride was replaced by the distillation residue obtained above. | |
8 EXAMPLE 8 When the reaction was repeated and the onium compound increased to a one mol percent level (based on diethyl malonate), the yield was increased to 72.5%. Tri-n-butylhexadecylphosphonium bromide was substituted for the tricaprylylmethylammonium chloride at the 1.0 mol % level and diethyl 2-vinylcyclopropane-1,1-dicarboxylate obtained in 73.2% yield. | ||
With potassium hydroxide In methanol; benzene | I EXAMPLE I EXAMPLE I To illustrate the preparation of diethyl 2-vinylcyclopropane-1,1-dicarboxylate via malonic ester condensation, the following experiment was conducted: To a glass reactor equipped with a mechanical stirrer, thermometer and condenser with water-trap were charged 12.5 gms (0.1 mol) trans-1,4-dichlorobutene-2, 16 gms (0.1 mol) diethylmalonate, 100 ml. benzene and 0.44 gms dicyclohexano-18-crown-6 (1.2 mol % based on diethylmalonate). Several drops methanol and 6.6 gms crushed potassium hydroxide (85%) were then added with stirring. A mild exotherm (40° C.) was noted and after about one hour insoluble organic salts began to precipitate from solution. Gas chromatographic analysis of the reaction mixture indicated about 20% conversion of the desired product at this point. The reaction mixture was then heated for an additional hour at 80° C. while removing benzene/water azeotrope and conversion to the desired diethyl 2-vinylcyclopropane-1,1-dicarboxylate was increased to 40%. Two additional charges (3 gms each) of potassium hydroxide were made so that the total amount of KOH used for the reaction was 0.206 mol. |
Multi-step reaction with 2 steps 1: piperidine; acetic acid / toluene / 12 h / Reflux; Inert atmosphere 2: tetrahydrofuran; mineral oil / 4.5 h / 20 - 50 °C / Inert atmosphere |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
77.9% | With potassium hydroxide; In dichloromethane; | EXAMPLE 32 To demonstrate the ability to vary the method of addition, diethyl malonate (160 g; 1.0 mol) was slowly charged to a reactor with external cooling means containing 137.5 g (1.10 mol) trans 1,4-dichlorobutene-2, 125 g (2.0 mol) flaked KOH (90%), 300 cc methylene chloride and 21 g (5 mol %) of tricaprylylmethylammonium chloride. The reaction mixture was stirred during the addition and temperature maintained at 25 C. with external cooling. At the completion of the reaction the resulting crude product obtained following the usual workup procedure was fractionally distilled and 165.3 g diethyl 2-vinylcyclopropane-1,1-dicarboxylate (77.9% yield) recovered. |
65.7% | With potassium hydroxide; In benzene; | EXAMPLE 8 To illustrate yet another variation of the present process a reaction vessel fitted with a suitable stirrer, Dean-Stark trap, and condenser was charged with 866 g (6.9 mol) trans 1,4-dichlorobutene-2, 640 g (4.0 mol) diethyl malonate, 1.2 g (0.08 mol percent based on malonate) tricaprylylmethylammonium chloride and 1.8 liters benzene. The reactor and its contents were heated to 60 C. with stirring and incremental additions of flaked solid (85%) potassium hydroxide made over a 4.75-hour period while azeotropically removing water of reaction. A total of 528 grams solid KOH were charged. After 5.5 hours the theoretical amount of water was removed and the reaction mixture was cooled, filtered to remove potassium salts and the benzene solution concentrated. The crude brown oil, upon distillation at reduced pressure, yielded the desired diethyl 2-vinylcyclopropane-1,1-dicarboxylate (65.7% yield). |
110.0 g (51.9%) | With sodium hydroxide; In dichloromethane; water; | EXAMPLE 6 To demonstrate the use of solid caustic for the process of this invention 137.5 g (1.10 mol) trans 1,4-dichlorobutene-2, 160.0 g (1.0 mol) diethyl malonate and 20.2 g (5 mol % based on malonate) tricaprylylmethylammonium chloride were dissolved in 600 cc methylene chloride. Sodium hydroxide (97.3%) pellets (82.2 g; 2.0 mol) were added to the stirred solution in small portions while maintaining the temperature of reaction 18-24 C. A mild exotherm was observed with the initial addition of caustic and became more pronounced with subsequent additions of the base. Frequent external cooling was provided until the KOH addition was complete (1.5 hours). The reaction mixture was stirred for an additional 2.5 hours after which time water was added and the organic layer separated, concentrated and distilled at reduced pressure to afford 110.0 g (51.9%) of the desired diethyl 2-vinylcyclopropane-1,1-dicarboxylate. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
59.8% | With potassium hydroxide In dichloromethane | 28 EXAMPLE 28 EXAMPLE 28 The following experiment demonstrates the in situ preparation of the onium compound in the process. In a reaction flask were added 137.5 g (1.1 mol) trans 1,4-dichlorobutene-2, 160.0 g (1.0 mol) diethyl malonate, 600 cc methylene chloride and 6.8 g (5 mol % based on diethyl malonate) N,N-dimethylbenzylamine. The mixture was stirred at ambient temperature for 20 minutes and 124.8 g (2.0 mol) flaked 90% potassium hydroxide then added in small portions over a one-hour period while maintaining the reaction temperature at 25° C. with external cooling. The reaction was then stirred at ambient temperature for four hours. Diethyl 2-vinylcyclopropane-1,1-dicarboxylate (126.6 g; 59.8% yield) was obtained. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | 6 EXAMPLE 6 EXAMPLE 6 Under the same conditions of Example 1, there are reacted 0.013 g of Pd(PPh3)4 with 0.84 g of 1,1-dicarboethoxy-2-vinylcyclopropane and 0.860 g of diethylamine. After 24 hours at room temperature, the reaction mixture is distilled under vacuum and there is obtained 1.1 g of (5,5-dicarboethoxy-2-pentenyl) diethylamine, corresponding to an analytical yield of about 100% and to a catalytic efficiency of 343 mols of product per mol of palladium complex. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90% | In dimethyl sulfoxide B complex treated with ligand in DMSO at 40°C in the presence ofPd catalyst (5 mol%), reacted for 3 h, treated with diethanoltriamine; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95% | With sodium hydride In tetrahydrofuran at 0 - 78℃; for 12h; Inert atmosphere; | |
95% | With sodium hydride In tetrahydrofuran at 0 - 78℃; for 12h; Inert atmosphere; | |
90% | With sodium hydride In tetrahydrofuran at 70℃; |
90% | With sodium hydride In tetrahydrofuran; mineral oil at 20 - 70℃; for 16h; | |
Stage #1: diethyl malonate With sodium hydride In tetrahydrofuran at 0℃; for 1h; Stage #2: 1,4-dibromo-2-butene In tetrahydrofuran at 0 - 20℃; for 1h; | ||
With sodium hydride In tetrahydrofuran | ||
With caesium carbonate In tetrahydrofuran at 60℃; Inert atmosphere; | Synthesis of vinylcyclopropanes General procedure: The corresponding active methylene compound (2 mmol, 1 equiv.) and 1,4-dibromobut-2-ene (1 equiv.) were added to a round bottom flask with a stir bar under nitrogen atmosphere. To this, THF (0.2 M) and Cesium carbonate (2.5 equiv.) were added. After fitting the condenser, reaction mixture was stirred for overnight at 60°C. After cooling to room temperature, the reaction mixture was filtered over Celite and washed with diethyl ether. The organic phase was washed with saturated aqueous NaHCO3, followed by water and brine. After filtration over Na2SO4, the solvent was removed under reduced pressure. The crude product was purified by silica gel column chromatography using hexane and ethyl acetate as the eluent. Corresponding vinylcyclopropanes were obtained as solid/liquid with good yields. | |
With caesium carbonate In tetrahydrofuran at 60℃; for 16h; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
74% | With BF4(1-)*C10H13ClPdSe2(1+); water; toluene-4-sulfonic acid; bis(pinacol)diborane In methanol; dimethyl sulfoxide at 70℃; for 24h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
69% | With BF4(1-)*C10H13ClPdSe2(1+); water; toluene-4-sulfonic acid; bis(pinacol)diborane In methanol; dimethyl sulfoxide at 70℃; for 24h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Stage #1: diethyl malonate With sodium ethanolate In ethanol; toluene at 20℃; for 0.5h; Stage #2: (Z)-1,4-Ditosyloxy-2-butene In ethanol; toluene at 20℃; for 3.5h; Stage #3: With sodium hydroxide In ethanol; water; toluene for 1h; | 3 [Reference Example 3] Production of 1,1-di-ethoxycarbonyl-2-vinylcyclopropane 8.79 g (54.9 mmol) of diethyl malonate and 99 mL of toluene were added into a three-necked flask (300 mL), and thereafter, 20.5 mL (52.4 mmol) of a 20% sodium ethoxide ethanol solution was added thereto as a base. The obtained mixture was stirred at room temperature for 0.5 hours. Thereafter, 9.89 g (24.9 mmol) of cis-1,4-di-4-toluenesulfonyloxy-2-butene, which had been obtained by performing the same operations as those in Example 1 and then purifying the obtained compound by silica gel chromatography, was added to the reaction solution. The obtained mixture was stirred at room temperature for 3.5 hours, and thereafter, 59.9 mL of a 1 M sodium hydroxide aqueous solution was added to the reaction solution. The obtained mixture was stirred for 1 hour, and an organic layer was then separated. A water layer was re-extracted with 50 mL of toluene, and organic layers were gathered. The gathered organic layer was washed with 50 mL of water three times, and the resultant was then filtrated, while washing the residue with toluene. The obtained filtrate was concentrated at 45°C under reduced pressure, so as to obtain 22.4 g of 1,1-di-ethoxycarbonyl-2-vinylcyclopropane in the form of a crude product of a light yellow oily substance. This crude product contained 1.25 g of 1,1-di-ethoxycarbonyl-2-vinylcyclopropane (yield: 24%) and 3.94 g of 1,1-di-ethoxycarbonyl-3-vinylcyclopentene (yield: 74%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With water In dimethyl sulfoxide at 30℃; for 42h; Tris-HCl buffer; Enzymatic reaction; | 12 [Example 12] Production of (2S)-1,1-di-ethoxycarbonyl-2-vinylcyclopropane 250 mL of desalted water, 100 mL of Rhizomucor miehei-derived lipase (purchased from Sigma-Aldrich), and 50 mL of solution prepared by dissolving 1,1-di-ethoxycarbonyl-2-vinylcyclopropane which had been obtained in the same manner as that of Example 7 in dimethyl sulfoxide to a concentration of 100 g/L, were added to 100 mL of a 1 M Tris-HCl buffer (pH 7.5). Using a 1-L jar fermenter (manufactured by Able; model: BMJ), the obtained mixture was reacted at 30°C at a stirring rate of 350 rpm for 42 hours. After completion of the reaction, 500 mL of the reaction solution was extracted with 1 L of ethyl acetate, and the quantification of 1,1-di-ethoxycarbonyl-2-vinylcyclopropane remaining in the reaction solution and the measurement of optical purity were then carried out. As for the quantification, the ethyl acetate extract was measured using gas chromatography (GC). As for the optical purity, an aliquot of the ethyl acetate extract was concentrated and dried, the obtained product was then dissolved in ethanol to prepare a solution, and the solution was then measured using liquid chromatography (HPLC). As a result of the analyses, the content of the (2S)-1,1-di-ethoxycarbonyl-2-vinylcyclopropane was found to be 682 mg, and the optical purity was found to be 96.9%e.e. The obtained ethyl acetate solution was concentrated to a volume of 50 mL, and the concentrate was then washed with 30 mL of saturated sodium bicarbonate water three times, and then with 30 mL of brine once. The resultant was dried over anhydrous magnesium sulfate and was then concentrated. HPLC optical purify analysis conditions are as follows. Column: Chiralpak IC (4.6 mm × 250 mm; particle diameter: 5 µm) manufactured by Daicel Corporation, mobile phase: n-hexane 100/ethanol 2 (v/v), flow rate: 0.5 mL/min, column temperature: 35°C, UV: 210 nm |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
97% | With C8H18BrI2Sn(2-)*BrMg(1+) In dichloromethane at 25℃; for 1h; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
99% | With tris(dibenzylideneacetone)dipalladium(0) chloroform complex; C29H29N2OPS; 1,8-diazabicyclo[5.4.0]undec-7-ene In dichloromethane at 20℃; for 24h; Sealed tube; diastereoselective reaction; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With N-benzyl-N,N,N-triethylammonium chloride; potassium carbonate In acetonitrile at 60℃; for 6h; | Synthesis of substituted carboxylates (general proce-dure). General procedure: A mixture of 0.1 mol of -acid 1, 0.15 mol of 1,4-dichlorobut-2-ene 2 or 3,4-dichlorobut-1-ene 6, 0.1 mol of K 2 CO 3 , 80 mL of anhydrous acetonitrile, and 10 wt% of triethylbenzylammonium chloride was stirred at 60° during 6 h. In the case of microwave-assisted synthesis, the reaction duration was reduced to 1-2 h. After the reaction was complete the mixture was poured into water, extracted with methylene chloride, dried over Na 2 SO 4 , and evaporated. The residue was distilled in a vacuum or purified by chromatography of silica gel (1c, eluent: benzene-ethyl acetate, 8 : 2). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
84.615 % de | With silver hexafluoroantimonate; 1-Adamantanecarboxylic acid; tris(acetonitrile)pentamethylcyclopentadienylrhodium(III) hexafluoroantimonate In methanol at 90℃; for 12h; Inert atmosphere; Schlenk technique; Overall yield = 78 %; | 2 Example 2: The compound (E)-2-(4-(2-methyl-1-(2-pyrimidinyl) 7-carbolinyl) 2-buten-1-yl)malonate diethyl ester of the present example The structural formula is: The preparation method comprises the following steps: adding 0.2 mmol of N-pyrimidine porphyrin compound and 0.3 mmol of ethylene cyclopropane compound to a 35 mL Shrek tube under an argon atmosphere.0.002 mmol of [Cp*Rh(CH3CN)3](SbF6)2,0.02 mmol of 1-adamantanic acid, 0.04 mmol of silver hexafluoroantimonate, 0.5 mL of methanol, and reacted at 90 ° C for 12 hours; after completion of the reaction, it was rinsed with ethyl acetate, concentrated under reduced pressure and chromatographed (200-300 mesh silica gel) , eluent: ethyl acetate / petroleum ether gradient elution, ratio from 0/100 to 100 / 0), dried to pale yellow oil, yield 78%, E / Z = 12:1. |
84.615 % de | With silver hexafluoroantimonate; tris(acetonitrile)(η5-pentamethylcyclopentadienyl)rhodium(III) hexafluoroantimonate; 1-Adamantanecarboxylic acid In methanol at 90℃; for 12h; Inert atmosphere; Overall yield = 88 %; Overall yield = 74.5 mg; diastereoselective reaction; | |
77.778 % de | With silver hexafluoroantimonate; [ruthenium(II)(η6-1-methyl-4-isopropyl-benzene)(chloride)(μ-chloride)]2; mesitylenecarboxylic acid at 25℃; for 2h; Microwave irradiation; Overall yield = 68 percent; | 2 Example 2 Compound (E)-2-(4-(2-methyl-1-(2-pyrimidinyl)-7-indolinyl)-2-buten-1-yl)malonic acid diethyl ester The structural formula is: The preparation method is:In an air atmosphere,Add 0.2 mmol of N-pyrimidindolline compound to the microwave reaction tube,0.2 mmol of ethylene cyclopropane compound,0.01mmol of [Ru (p-cymene) Cl2] 2,0.02mmol mesitylene,0.04mmol of silver hexafluoroantimonate, microwave reaction at 25 ° C for 2 hours;After completion of the reaction, rinse with ethyl acetate.Chromatographic separation after concentration under reduced pressure (silica gel 200-300 mesh, eluent: ethyl acetate / petroleum ether gradient elution, ratio from 0/100 to 100/0)Dried to a pale yellow oil,Yield 68%, E / Z = 8: 1. |
83.333 % de | With silver hexafluoroantimonate; tris(acetonitrile)(η5-pentamethylcyclopentadienyl)rhodium(III) hexafluoroantimonate at 80℃; for 2h; Microwave irradiation; Overall yield = 92 percent; diastereoselective reaction; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
87.5 % de | With silver hexafluoroantimonate; 1-Adamantanecarboxylic acid; tris(acetonitrile)pentamethylcyclopentadienylrhodium(III) hexafluoroantimonate In methanol at 90℃; for 12h; Inert atmosphere; Schlenk technique; Overall yield = 77 %; | 3 Example 3: The compound (E)-2-(4-(3-methyl-1-(2-pyrimidinyl)7-indolyl)2-buten-1-yl)malonate diethyl ester of the present example The structural formula is: The preparation method comprises the following steps: adding 0.2 mmol of N-pyrimidine porphyrin compound and 0.3 mmol of ethylene cyclopropane compound to a 35 mL Shrek tube under an argon atmosphere.0.016 mmol of [Cp*Rh(CH3CN)3](SbF6)2,0.06 mmol of 1-adamantanic acid, 0.02 mmol of silver hexafluoroantimonate, methanol 0.5 mL, and reacted at 90 ° C for 12 hours; after completion of the reaction, it was rinsed with ethyl acetate, concentrated under reduced pressure and chromatographed (200-300 mesh silica gel) , eluent: ethyl acetate / petroleum ether gradient elution, ratio from 0/100 to 100 / 0), dried to pale yellow oil, yield 77%, E / Z = 15:1. |
87.5 % de | With silver hexafluoroantimonate; tris(acetonitrile)(η5-pentamethylcyclopentadienyl)rhodium(III) hexafluoroantimonate; 1-Adamantanecarboxylic acid In methanol at 90℃; for 12h; Inert atmosphere; Overall yield = 87 %; Overall yield = 73.6 mg; diastereoselective reaction; | |
87.5 % de | With silver hexafluoroantimonate; [ruthenium(II)(η6-1-methyl-4-isopropyl-benzene)(chloride)(μ-chloride)]2; mesitylenecarboxylic acid at 25℃; for 2h; Microwave irradiation; Overall yield = 67 percent; | 3 Example 3 Compound (E)-2-(4-(3-methyl-1-(2-pyrimidinyl)-7-indolinyl)-2-buten-1-yl)malonic acid diethyl ester The structural formula is: The preparation method is:In an air atmosphere,Add 0.2 mmol of N-pyrimidindolline compound to the microwave reaction tube,0.3mmol of ethylene cyclopropane compound,0.02mmol of [Ru (p-cymene) Cl2] 2,0.06 mmol of mesitylene,0.02mmol of silver hexafluoroantimonate,Microwave reaction at 25 for 2 hours;After the reaction, rinse with ethyl acetate, concentrate under reduced pressure and chromatograph (silica gel 200-300 mesh, eluent: ethyl acetate / petroleum ether gradient elution, the ratio is from 0/100 to 100/0),Dried to a pale yellow oil,Yield 67%, E / Z = 15: 1. |
77.778 % de | With silver hexafluoroantimonate; tris(acetonitrile)(η5-pentamethylcyclopentadienyl)rhodium(III) hexafluoroantimonate at 80℃; for 2h; Microwave irradiation; Overall yield = 90 percent; diastereoselective reaction; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
50 % de | With silver hexafluoroantimonate; 1-Adamantanecarboxylic acid; tris(acetonitrile)pentamethylcyclopentadienylrhodium(III) hexafluoroantimonate In methanol at 80℃; for 12h; Inert atmosphere; Schlenk technique; Overall yield = 67 %; | 4 Example 4: The compound (E)-2-(4-(2-phenyl-1-(2-pyrimidinyl)7-indolyl)2-buten-1-yl)malonate diethyl ester of the present example The structural formula is: The preparation method comprises: adding 0.2 mmol of N-pyrimidine porphyrin compound and 0.2 mmol of ethylene cyclopropane compound to a 35 mL Shrek tube under an argon atmosphere.0.016 mmol of [Cp*Rh(CH3CN)3](SbF6)2,0.1 mmol of 1-adamantanic acid, 0.04 mmol of silver hexafluoroantimonate, methanol 0.5 mL, and reacted at 80 ° C for 12 hours; after completion of the reaction, it was rinsed with ethyl acetate, concentrated under reduced pressure and chromatographed (200-300 mesh silica gel) , eluent: ethyl acetate / petroleum ether gradient elution, ratio from 0/100 to 100 / 0), dried to pale yellow oil, yield 67%, E / Z = 3:1. |
71.429 % de | With silver hexafluoroantimonate; tris(acetonitrile)(η5-pentamethylcyclopentadienyl)rhodium(III) hexafluoroantimonate; 1-Adamantanecarboxylic acid In methanol at 90℃; for 12h; Inert atmosphere; Overall yield = 77 %; Overall yield = 74.7 mg; diastereoselective reaction; | |
With silver hexafluoroantimonate; tris(acetonitrile)(η5-pentamethylcyclopentadienyl)rhodium(III) hexafluoroantimonate; 1-Adamantanecarboxylic acid In methanol at 90℃; for 12h; Inert atmosphere; Sealed tube; Glovebox; Overall yield = 77 percent; Overall yield = 74.7 mg; regioselective reaction; |
50 % de | With silver hexafluoroantimonate; [ruthenium(II)(η6-1-methyl-4-isopropyl-benzene)(chloride)(μ-chloride)]2; mesitylenecarboxylic acid at 25℃; for 2h; Microwave irradiation; Overall yield = 67 percent; | 4 Example 4 Compound (E)-2-(4-(2-phenyl-1-(2-pyrimidinyl)-7-indolinyl)-2-buten-1-yl)malonic acid diethyl ester in this example The structural formula is: The preparation method is: in an air atmosphere,Add 0.2 mmol of N-pyrimidindolline compound to the microwave reaction tube,0.4mmol of ethylene cyclopropane compound,0.01mmol of [Ru (p-cymene) Cl2] 2,0.1mmol mesotrimethylbenzoic acid,0.08 mmol of silver hexafluoroantimonate,Microwave reaction at 25 for 2 hours;After completion of the reaction, rinse with ethyl acetate.Chromatographic separation after concentration under reduced pressure (silica gel 200-300 mesh, eluent: ethyl acetate / petroleum ether gradient elution, ratio from 0/100 to 100/0)Drying to a pale yellow oil, yield 67%,E / Z = 3: 1. |
75 % de | With silver hexafluoroantimonate; [ruthenium(II)(η6-1-methyl-4-isopropyl-benzene)(chloride)(μ-chloride)]2; mesitylenecarboxylic acid at 25℃; for 2h; Microwave irradiation; Overall yield = 90 percent; diastereoselective reaction; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
87.5 % de | With silver hexafluoroantimonate; 1-Adamantanecarboxylic acid; tris(acetonitrile)pentamethylcyclopentadienylrhodium(III) hexafluoroantimonate In methanol at 100℃; for 12h; Inert atmosphere; Schlenk technique; Overall yield = 72 %; | 5 Example 5: The compound (E)-2-(4-(4-methyl-1-(2-pyrimidinyl)7-indolyl) 2-buten-1-yl)malonate diethyl ester of the present example The structural formula is: The preparation method comprises the following steps: adding 0.2 mmol of N-pyrimidine porphyrin compound and 0.4 mmol of ethylene cyclopropane compound to a 35 mL Shrek tube under an argon atmosphere.0.02 mmol of [Cp*Rh(CH3CN)3](SbF6)2,0.1 mmol of 1-adamantanic acid, 0.04 mmol of silver hexafluoroantimonate, methanol 0.5 mL, and reacted at 100 ° C for 12 hours; after completion of the reaction, it was rinsed with ethyl acetate, concentrated under reduced pressure and chromatographed (200-300 mesh silica gel) , eluent: ethyl acetate / petroleum ether gradient elution, ratio from 0/100 to 100 / 0), dried to pale yellow oil, yield 72%, E / Z = 15:1. |
87.5 % de | With silver hexafluoroantimonate; tris(acetonitrile)(η5-pentamethylcyclopentadienyl)rhodium(III) hexafluoroantimonate; 1-Adamantanecarboxylic acid In methanol at 90℃; for 12h; Inert atmosphere; Overall yield = 80 %; Overall yield = 67.7 mg; diastereoselective reaction; | |
87.5 % de | With silver hexafluoroantimonate; [ruthenium(II)(η6-1-methyl-4-isopropyl-benzene)(chloride)(μ-chloride)]2; mesitylenecarboxylic acid at 25℃; for 2h; Microwave irradiation; Overall yield = 72 percent; | 5 Example 5 Compound(E) -2- (4- (4-methyl-1- (2-pyrimidinyl) 7- indolinyl) 2- buten-1-yl) Malonic acid Diethyl ester The structural formula is: The preparation method is: in an air atmosphere,Add 0.2 mmol of N-pyrimidindolline compound to the microwave reaction tube,0.3mmol of ethylene cyclopropane compound,0.01mmol of [Ru (p-cymene) Cl2] 2,0.02mmol 1-adamantanic acid,0.04mmol of silver hexafluoroantimonate, microwave reaction at 25 ° C for 2 hours;After the reaction, rinse with ethyl acetate, concentrate under reduced pressure and chromatograph (silica gel 200-300 mesh, eluent: ethyl acetate / petroleum ether gradient elution, the ratio is from 0/100 to 100/0),Dried to a pale yellow oil,Yield: 72%, E / Z = 15: 1. |
85.714 % de | With silver hexafluoroantimonate; tris(acetonitrile)(η5-pentamethylcyclopentadienyl)rhodium(III) hexafluoroantimonate at 80℃; for 2h; Microwave irradiation; Overall yield = 91 percent; diastereoselective reaction; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
85.714 % de | With silver hexafluoroantimonate; 1-Adamantanecarboxylic acid; tris(acetonitrile)pentamethylcyclopentadienylrhodium(III) hexafluoroantimonate In methanol at 90℃; for 12h; Inert atmosphere; Schlenk technique; Overall yield = 81 %; | 6 Example 6: The compound (E)-2-(4-(4-methoxy-1-(2-pyrimidinyl)7-indolyl) 2-butene-1- in this exampleThe structural formula of diethyl malonate is: The preparation method comprises the following steps: adding 0.2 mmol of N-pyrimidine porphyrin compound and 0.3 mmol of ethylene cyclopropane compound to a 35 mL Shrek tube under an argon atmosphere.0.004 mmol of [Cp*Rh(CH3CN)3](SbF6)2,0.06 mmol of 1-adamantanic acid, 0.06 mmol of silver hexafluoroantimonate, 2 mL of methanol, and reacted at 90 ° C for 12 hours; after completion of the reaction, it was washed with ethyl acetate, concentrated under reduced pressure, and then chromatographed (200-300 mesh silica gel, Eluent: Ethyl acetate / petroleum ether gradient elution, ratio: 0/100 to 100/0), dried to pale yellow oil, yield 81%, E/Z = 13:1. |
84.615 % de | With silver hexafluoroantimonate; tris(acetonitrile)(η5-pentamethylcyclopentadienyl)rhodium(III) hexafluoroantimonate; 1-Adamantanecarboxylic acid In methanol at 90℃; for 12h; Inert atmosphere; Overall yield = 84 %; Overall yield = 73.8 mg; diastereoselective reaction; | |
85.714 % de | With silver hexafluoroantimonate; [ruthenium(II)(η6-1-methyl-4-isopropyl-benzene)(chloride)(μ-chloride)]2; mesitylenecarboxylic acid at 25℃; for 2h; Microwave irradiation; Overall yield = 81 percent; | 6 Example 6 Compound (E)-2-(4-(4-methoxy-1-(2-pyrimidinyl)-7-indolinyl)-2-buten-1-yl)malonic acid diethyl ester The structural formula of the ester is: The preparation method is: in an air atmosphere,Add 0.2 mmol of N-pyrimidindolline compound to the microwave reaction tube,0.3mmol of ethylene cyclopropane compound,0.008mmol of [Ru (p-cymene) Cl2] 2,0.06 mmol of mesitylene,0.06mmol of silver hexafluoroantimonate, microwave reaction at 25 ° C for 2 hours;After the reaction, rinse with ethyl acetate, concentrate under reduced pressure and chromatograph (silica gel 200-300 mesh, eluent: ethyl acetate / petroleum ether gradient elution, the ratio is from 0/100 to 100/0),Dried to a pale yellow oil,Yield: 81%, E / Z = 13: 1. |
85.714 % de | With silver hexafluoroantimonate; tris(acetonitrile)(η5-pentamethylcyclopentadienyl)rhodium(III) hexafluoroantimonate at 80℃; for 2h; Microwave irradiation; Overall yield = 86 percent; diastereoselective reaction; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
87% | With silver hexafluoroantimonate; 1-Adamantanecarboxylic acid; tris(acetonitrile)pentamethylcyclopentadienylrhodium(III) hexafluoroantimonate In methanol at 110℃; for 12h; Inert atmosphere; Schlenk technique; | 7 Example 17: The compound (E) 2-(4-(4-bromo-1-(2-pyrimidinyl) 7-indolyl) 2-buten-1-yl)malonate of the present example The structural formula is: Preparation method: adding 0.2 mmol of N-pyrimidine porphyrin to 35 mL Shrek tube under argon atmosphereCompound, 0.4 mmol of ethylene cyclopropane compound, 0.008 mmol of [Cp*Rh(CH3CN)3](SbF6)2, 0.06 mmol 1-goldCycloalkane, 0.04mmol of silver hexafluoroantimonate, 1mL of methanol, reacted at 110 ° C for 12 hours; after the reaction, use ethyl acetateRinse, concentrate under reduced pressure and chromatographically separate (200-300 mesh silica gel, eluent: ethyl acetate / petroleum ether gradient elution, ratio 0/100 to 100/0), dry to pale yellow oil, yield 87%, E/Z > 20:1. |
87% | With silver hexafluoroantimonate; [ruthenium(II)(η6-1-methyl-4-isopropyl-benzene)(chloride)(μ-chloride)]2; mesitylenecarboxylic acid at 30℃; for 1h; Microwave irradiation; | 7 Example 7 Compound (E)-2-(4-(4-bromo-1-(2-pyrimidinyl)-7-indolinyl)-2-buten-1-yl)malonic acid diethyl ester in this example The structural formula is: Preparation method: In air atmosphere,Add 0.2mmol of N-pyrimidindolline compound to the Weibo reflection tube,0.4mmol of ethylene cyclopropane compound,0.008mmol of [Ru (p-cymene) Cl2] 2,0.06 mmol of mesitylene,0.04 mmol of silver hexafluoroantimonate,Microwave reaction at 30 ° C for 1 hour;After completion of the reaction, rinse with ethyl acetate.Chromatographic separation after concentration under reduced pressure (silica gel 200-300 mesh, eluent: ethyl acetate / petroleum ether gradient elution, ratio from 0/100 to 100/0)Drying to a pale yellow oil, 87% yield, E / Z> 20: 1. |
60% | With silver hexafluoroantimonate; tris(acetonitrile)(η5-pentamethylcyclopentadienyl)rhodium(III) hexafluoroantimonate; 1-Adamantanecarboxylic acid In methanol at 90℃; for 12h; Inert atmosphere; diastereoselective reaction; |
60% | With silver hexafluoroantimonate; tris(acetonitrile)(η5-pentamethylcyclopentadienyl)rhodium(III) hexafluoroantimonate; 1-Adamantanecarboxylic acid In methanol at 90℃; for 12h; Inert atmosphere; Sealed tube; Glovebox; regioselective reaction; | |
54% | With silver hexafluoroantimonate; [ruthenium(II)(η6-1-methyl-4-isopropyl-benzene)(chloride)(μ-chloride)]2; mesitylenecarboxylic acid at 25℃; for 2h; Microwave irradiation; diastereoselective reaction; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
83.333 % de | With silver hexafluoroantimonate; 1-Adamantanecarboxylic acid; tris(acetonitrile)pentamethylcyclopentadienylrhodium(III) hexafluoroantimonate In methanol at 120℃; for 12h; Inert atmosphere; Schlenk technique; Overall yield = 75 %; | 8 Example 8: The compound (E)-2-(4-(5-methyl-1-(2-pyrimidinyl)7-indolyl)2-buten-1-yl)malonate diethyl ester of the present example The structural formula is: Preparation method: Under an argon atmosphere, add 0.2 mmol of N-pyrimidine porphyrin compound, 0.2 mmol of ethylene cyclopropane compound, and 0.006 mmol of [Cp*Rh(CH3CN)3] (SbF6) to a 35 mL Shrek tube. 2, 0.06 mmol of 1-adamantanic acid, 0.04 mmol of silver hexafluoroantimonate, 2 mL of methanol, and reacted at 120 ° C for 12 hours; after completion of the reaction, it was rinsed with ethyl acetate, concentrated under reduced pressure and chromatographed (silica gel 200- 300 mesh, eluent: ethyl acetate / petroleum ether gradient elution, ratio from 0/100 to 100/0), dried to pale yellow oil, yield 75%, E / Z = 11:1. |
83.333 % de | With silver hexafluoroantimonate; tris(acetonitrile)(η5-pentamethylcyclopentadienyl)rhodium(III) hexafluoroantimonate; 1-Adamantanecarboxylic acid In methanol at 90℃; for 12h; Inert atmosphere; Overall yield = 83 %; Overall yield = 71.1 mg; diastereoselective reaction; | |
83.333 % de | With silver hexafluoroantimonate; [ruthenium(II)(η6-1-methyl-4-isopropyl-benzene)(chloride)(μ-chloride)]2; mesitylenecarboxylic acid at 40℃; for 2h; Microwave irradiation; Overall yield = 75 percent; | 8 Example 8 Compound (E)-2-(4-(5-methyl-1-(2-pyrimidinyl)-7-indolyl)-2-buten-1-yl)malonic acid diethyl ester The structural formula is: Preparation method: In air atmosphere,Add 0.2 mmol of N-pyrimidindolline compound to the microwave reaction tube,0.2 mmol of ethylene cyclopropane compound,0.006mmol of [Ru (p-cymene) Cl2] 2,0.06 mmol of mesitylene,0.04mmol of silver hexafluoroantimonate, microwave reaction at 40 ° C for 2 hours;After completion of the reaction, rinse with ethyl acetate.Chromatographic separation after concentration under reduced pressure (silica gel 200-300 mesh, eluent: ethyl acetate / petroleum ether gradient elution, ratio from 0/100 to 100/0)Dried to a pale yellow oil,Yield 75%, E / Z = 11: 1. |
83.333 % de | With silver hexafluoroantimonate; [ruthenium(II)(η6-1-methyl-4-isopropyl-benzene)(chloride)(μ-chloride)]2; mesitylenecarboxylic acid at 25℃; for 2h; Microwave irradiation; Overall yield = 86 percent; diastereoselective reaction; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90% | With silver hexafluoroantimonate; [ruthenium(II)(η6-1-methyl-4-isopropyl-benzene)(chloride)(μ-chloride)]2; mesitylenecarboxylic acid at 25℃; for 2h; Microwave irradiation; diastereoselective reaction; | |
79% | With silver hexafluoroantimonate; tris(acetonitrile)(η5-pentamethylcyclopentadienyl)rhodium(III) hexafluoroantimonate; 1-Adamantanecarboxylic acid In methanol at 90℃; for 12h; Inert atmosphere; diastereoselective reaction; | |
79% | With silver hexafluoroantimonate; tris(acetonitrile)(η5-pentamethylcyclopentadienyl)rhodium(III) hexafluoroantimonate; 1-Adamantanecarboxylic acid In methanol at 90℃; for 12h; Inert atmosphere; Sealed tube; Glovebox; regioselective reaction; |
76% | With silver hexafluoroantimonate; 1-Adamantanecarboxylic acid; tris(acetonitrile)pentamethylcyclopentadienylrhodium(III) hexafluoroantimonate In methanol at 100℃; for 12h; Inert atmosphere; Schlenk technique; | 9 Example 9: Compound of the present embodiment is (E)-2- (4- (5-methoxy-1- (2-pyrimidinyl) 7-indolinyl) of 2-buten-1-yl) malonic acid diethyl ester of the formula: Compound of the present embodiment is (E)-2- (4- (5-methoxy-1- (2-pyrimidinyl) 7-indolinyl) of 2-buten-1-yl) malonic acid diethyl ester of the formula:Preparation method: under an argon atmosphere, add 0.2 mmol of N-pyrimidine porphyrin compound, 0.24 mmol of ethylene cyclopropane compound to a 35 mL Shrek tube.0.003 mmol of [Cp*Rh(CH3CN)3](SbF6)2,0.06 mmol of 1-adamantanic acid, 0.04 mmol of silver hexafluoroantimonate, 1 mL of methanol, and reacted at 100 ° C for 12 hours; after completion of the reaction, it was rinsed with ethyl acetate, concentrated under reduced pressure and then chromatographed (200-300 mesh silica gel, Eluent: Ethyl acetate/petroleum ether gradient elution, ratio: 0/100 to 100/0), dried to pale yellow oil, yield 76%, E/Z > 20:1. |
76% | With silver hexafluoroantimonate; [ruthenium(II)(η6-1-methyl-4-isopropyl-benzene)(chloride)(μ-chloride)]2; mesitylenecarboxylic acid at 50℃; for 2h; Microwave irradiation; | 9 Example 9 Compound (E)-2-(4-(5-methoxy-1-(2-pyrimidinyl)-7-indolinyl)-2-buten-1-yl)malonic acid diethyl ester The structural formula of the ester is: Preparation method: In air atmosphere,Add 0.2 mmol of N-pyrimidindolline compound to the microwave reaction tube,0.24 mmol of ethylene cyclopropane compound,0.003 mmol of [Ru (p-cymene) Cl2] 2, 0.06 mmol of 1-adamantanic acid,0.04 mmol of silver hexafluoroantimonate,Microwave at 50 ° C for 2 hours;After completion of the reaction, rinse with ethyl acetate.Chromatographic separation after concentration under reduced pressure (silica gel 200-300 mesh, eluent: ethyl acetate / petroleum ether gradient elution, ratio from 0/100 to 100/0)Dried to a pale yellow oil,The yield was 76% and E / Z> 20: 1. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90% | With silver hexafluoroantimonate; [ruthenium(II)(η6-1-methyl-4-isopropyl-benzene)(chloride)(μ-chloride)]2; mesitylenecarboxylic acid at 25℃; for 2h; Microwave irradiation; diastereoselective reaction; | |
80% | With silver hexafluoroantimonate; tris(acetonitrile)(η5-pentamethylcyclopentadienyl)rhodium(III) hexafluoroantimonate; 1-Adamantanecarboxylic acid In methanol at 90℃; for 12h; Inert atmosphere; diastereoselective reaction; | |
80% | With silver hexafluoroantimonate; tris(acetonitrile)(η5-pentamethylcyclopentadienyl)rhodium(III) hexafluoroantimonate; 1-Adamantanecarboxylic acid In methanol at 90℃; for 12h; Inert atmosphere; Sealed tube; Glovebox; regioselective reaction; |
70% | With silver hexafluoroantimonate; 1-Adamantanecarboxylic acid; tris(acetonitrile)pentamethylcyclopentadienylrhodium(III) hexafluoroantimonate In methanol at 90℃; for 12h; Inert atmosphere; Schlenk technique; | 10 Example 10: The compound (E)-2-(4-(5-chloro-1-(2-pyrimidinyl)7-indolyl)2-buten-1-yl)malonate diethyl ester of the present exampleThe structural formula is: Preparation method: Under an argon atmosphere, add 0.2 mmol of N-pyrimidine porphyrin compound, 0.36 mmol of ethylene cyclopropane compound, 0.02 mmol of [Cp*Rh(CH3CN)3] (SbF6) to a 35 mL Shrek tube. 2, 0.1 mmol of 1-adamantanic acid, 0.08 mmol of silver hexafluoroantimonate, 1 mL of methanol, and reacted at 90 ° C for 12 hours; after completion of the reaction, it was rinsed with ethyl acetate, concentrated under reduced pressure and chromatographed (silica gel 200- 300 mesh, eluent: ethyl acetate / petroleum ether gradient elution, ratio from 0/100 to 100/0), dried to pale yellow oil, yield 70%, E / Z > 20:1. |
70% | With silver hexafluoroantimonate; [ruthenium(II)(η6-1-methyl-4-isopropyl-benzene)(chloride)(μ-chloride)]2; mesitylenecarboxylic acid at 40℃; for 2h; Microwave irradiation; | 10 Example 10 Compound (E)-2-(4-(5-chloro-1-(2-pyrimidinyl)-7-indolinyl)-2-buten-1-yl)malonic acid diethyl ester of this example The structural formula is: Preparation method: In air atmosphere,Add 0.2 mmol of N-pyrimidindolline compound to the microwave reaction tube,0.36 mmol of ethylene cyclopropane compound, 0.02 mmol of [Ru (p-cymene) Cl2] 2, 0.1 mmol of mesitylene,0.08 mmol of silver hexafluoroantimonate,Microwave reaction at 40 ° C for 2 hours;After completion of the reaction, rinse with ethyl acetate.Chromatographic separation after concentration under reduced pressure (silica gel 200-300 mesh, eluent: ethyl acetate / petroleum ether gradient elution, ratio from 0/100 to 100/0)Dried to a pale yellow oil,Yield: 70%, E / Z> 20: 1. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
78% | With silver hexafluoroantimonate; 1-Adamantanecarboxylic acid; tris(acetonitrile)pentamethylcyclopentadienylrhodium(III) hexafluoroantimonate In methanol at 90℃; for 12h; Inert atmosphere; Schlenk technique; | 11 Example 11: The compound (E) 2-(4-(5-bromo-1-(2-pyrimidinyl)7-indolyl)2-buten-1-yl)malonate of the present example The structural formula is: Preparation method: under an argon atmosphere, add 0.2 mmol of N-pyrimidine porphyrin compound, 0.3 mmol of ethylene cyclopropane compound to a 35 mL Shrek tube.0.006 mmol of [Cp*Rh(CH3CN)3](SbF6)2,0.06 mmol of 1-adamantanic acid, 0.04 mmol of silver hexafluoroantimonate, 1 mL of methanol, and reacted at 90 ° C for 12 hours; after completion of the reaction, it was rinsed with ethyl acetate, concentrated under reduced pressure, and then chromatographed (200-300 mesh silica gel, Eluent: Ethyl acetate / petroleum ether gradient elution, ratio from 0/100 to 100/0), dried to pale yellow oil, yield 78%, E/Z > 20:1. |
78% | With silver hexafluoroantimonate; [ruthenium(II)(η6-1-methyl-4-isopropyl-benzene)(chloride)(μ-chloride)]2; mesitylenecarboxylic acid at 50℃; for 2h; Microwave irradiation; | 11 Example 11 Compound (E) -2- (4- (5-bromo-1- (2-pyrimidinyl) 7- indolinyl) 2- buten-1-yl) Malonic acid Diethyl ester of this example The structural formula is: Preparation method: In air atmosphere,Add 0.2 mmol of N-pyrimidindolline compound to the microwave reaction tube,0.3mmol of ethylene cyclopropane compound,0.006mmol of [Ru (p-cymene) Cl2] 2,0.06 mmol of mesitylene,0.04mmol of silver hexafluoroantimonate, microwave reaction at 50 ° C for 2 hours;After completion of the reaction, rinse with ethyl acetate.Chromatographic separation after concentration under reduced pressure (silica gel 200-300 mesh, eluent: ethyl acetate / petroleum ether gradient elution, ratio from 0/100 to 100/0)Dried to a pale yellow oil,Yield 78%, E / Z> 20: 1. |
73% | With silver hexafluoroantimonate; [ruthenium(II)(η6-1-methyl-4-isopropyl-benzene)(chloride)(μ-chloride)]2; mesitylenecarboxylic acid at 25℃; for 2h; Microwave irradiation; diastereoselective reaction; |
56% | With silver hexafluoroantimonate; tris(acetonitrile)(η5-pentamethylcyclopentadienyl)rhodium(III) hexafluoroantimonate; 1-Adamantanecarboxylic acid In methanol at 90℃; for 12h; Inert atmosphere; diastereoselective reaction; | |
56% | With silver hexafluoroantimonate; tris(acetonitrile)(η5-pentamethylcyclopentadienyl)rhodium(III) hexafluoroantimonate; 1-Adamantanecarboxylic acid In methanol at 90℃; for 12h; Inert atmosphere; Sealed tube; Glovebox; regioselective reaction; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
81% | With silver hexafluoroantimonate; 1-Adamantanecarboxylic acid; tris(acetonitrile)pentamethylcyclopentadienylrhodium(III) hexafluoroantimonate In methanol at 90℃; for 12h; Inert atmosphere; Schlenk technique; | 12 Example 12: The compound (E)-2-(4-(5-methylformate-1-(2-pyrimidinyl)7-indolyl)2-buten-1-yl)malonic acid diethyl ether of this example The structural formula of the ester is: Preparation method: under an argon atmosphere, add 0.2 mmol of N-pyrimidine porphyrin compound, 0.36 mmol of ethylene cyclopropane compound to a 35 mL Shrek tube.0.008 mmol of [Cp*Rh(CH3CN)3](SbF6)2, 0.08 mmol of 1-adamantanic acid, 0.04 mmol of silver hexafluoroantimonate, methanol 0.5 mL, reacted at 90 ° C for 12 hours; after the reaction, using acetic acid Ethyl ester was rinsed, concentrated under reduced pressure, and then chromatographed on silica gel (200-300 mesh, eluent: ethyl acetate / petroleum ether gradient elution, ratio: 0/100 to 100/0). The yield was 81% and E/Z > 20:1. |
81% | With silver hexafluoroantimonate; [ruthenium(II)(η6-1-methyl-4-isopropyl-benzene)(chloride)(μ-chloride)]2; mesitylenecarboxylic acid at 60℃; for 1h; Microwave irradiation; | 12 Example 12 Compound (E) -2- (4- (5-carboxylic acid methyl ester-1- (2-pyrimidinyl) 7-indololinyl) 2-buten-1-yl) malonate The structural formula of the ester is: Preparation method: In air atmosphere,Add 0.2 mmol of N-pyrimidindolline compound to the microwave reaction tube,0.36 mmol of ethylene cyclopropane compound,0.008mmol of [Ru (p-cymene) Cl2] 2,0.08 mmol mesitylene,0.04mmol of silver hexafluoroantimonate, microwave reaction at 60 ° C for 1 hour;After completion of the reaction, rinse with ethyl acetate.Chromatographic separation after concentration under reduced pressure (silica gel 200-300 mesh, eluent: ethyl acetate / petroleum ether gradient elution, ratio from 0/100 to 100/0)Dried to a pale yellow oil,Yield: 81%, E / Z> 20: 1. |
72% | With silver hexafluoroantimonate; tris(acetonitrile)(η5-pentamethylcyclopentadienyl)rhodium(III) hexafluoroantimonate; 1-Adamantanecarboxylic acid In methanol at 90℃; for 12h; Inert atmosphere; diastereoselective reaction; |
72% | With silver hexafluoroantimonate; tris(acetonitrile)(η5-pentamethylcyclopentadienyl)rhodium(III) hexafluoroantimonate; 1-Adamantanecarboxylic acid In methanol at 90℃; for 12h; Inert atmosphere; Sealed tube; Glovebox; regioselective reaction; | |
71% | With silver hexafluoroantimonate; tris(acetonitrile)(η5-pentamethylcyclopentadienyl)rhodium(III) hexafluoroantimonate at 80℃; for 2h; Microwave irradiation; diastereoselective reaction; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
79% | With silver hexafluoroantimonate; 1-Adamantanecarboxylic acid; tris(acetonitrile)pentamethylcyclopentadienylrhodium(III) hexafluoroantimonate In methanol at 90℃; for 12h; Inert atmosphere; Schlenk technique; | 13 Example 13: The compound (E) 2-(4-(6-chloro-1-(2-pyrimidinyl) 7-carbolinyl) 2-buten-1-yl)malonate of the present example The structural formula is: Preparation method: under an argon atmosphere, add 0.2 mmol of N-pyrimidine porphyrin compound, 0.3 mmol of ethylene cyclopropane compound to a 35 mL Shrek tube.0.02 mmol of [Cp*Rh(CH3CN)3](SbF6)2,0.06 mmol of 1-adamantanic acid, 0.04 mmol of silver hexafluoroantimonate, 1 mL of methanol, and reacted at 90 ° C for 12 hours; after completion of the reaction, it was rinsed with ethyl acetate, concentrated under reduced pressure, and then chromatographed (200-300 mesh silica gel, Eluent: Ethyl acetate / petroleum ether gradient elution, ratio from 0/100 to 100/0), dried to pale yellow oil, yield 79%, E/Z > 20:1. |
79% | With silver hexafluoroantimonate; [ruthenium(II)(η6-1-methyl-4-isopropyl-benzene)(chloride)(μ-chloride)]2; mesitylenecarboxylic acid at 70℃; for 1h; Microwave irradiation; | 13 Example 13 Compound (E) -2- (4- (6-chloro-1- (2-pyrimidinyl) 7-indolyl) 2-butene-1-yl) Malonic acid Diethyl ester in this example The structural formula is: Preparation method: In air atmosphere,Add 0.2 mmol of N-pyrimidindolline compound to the microwave reaction tube,0.3mmol of ethylene cyclopropane compound,0.02mmol of [Ru (p-cymene) Cl2] 2,0.06 mmol of mesitylene,0.04 mmol of silver hexafluoroantimonate,Microwave reaction at 70 for 1 hour;After completion of the reaction, rinse with ethyl acetate.Chromatographic separation after concentration under reduced pressure (silica gel 200-300 mesh, eluent: ethyl acetate / petroleum ether gradient elution, ratio from 0/100 to 100/0)Dried to a pale yellow oil,Yield: 79%, E / Z> 20: 1. |
71% | With silver hexafluoroantimonate; tris(acetonitrile)(η5-pentamethylcyclopentadienyl)rhodium(III) hexafluoroantimonate at 80℃; for 2h; Microwave irradiation; diastereoselective reaction; |
60% | With silver hexafluoroantimonate; tris(acetonitrile)(η5-pentamethylcyclopentadienyl)rhodium(III) hexafluoroantimonate; 1-Adamantanecarboxylic acid In methanol at 90℃; for 12h; Inert atmosphere; diastereoselective reaction; | |
60% | With silver hexafluoroantimonate; tris(acetonitrile)(η5-pentamethylcyclopentadienyl)rhodium(III) hexafluoroantimonate; 1-Adamantanecarboxylic acid In methanol at 90℃; for 12h; Inert atmosphere; Sealed tube; Glovebox; regioselective reaction; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
88% | With silver hexafluoroantimonate; 1-Adamantanecarboxylic acid; tris(acetonitrile)pentamethylcyclopentadienylrhodium(III) hexafluoroantimonate In methanol at 90℃; for 12h; Inert atmosphere; Schlenk technique; | 1 Example 1: Compound of this example (E) 2-(4-(1-(2-pyrimidinyl)7-indolyl)2-buten-1-yl)malonate The structural formula is The preparation method is: In an argon-protected environment, 0.2 mmol of N-pyrimidine porphyrin compound, 0.3 mmol of ethylene cyclopropane compound, was added to a 35 mL Shrek tube. 0.002 mmol of [Cp*Rh(CH3CN)3](SbF6)2, 0.04 mmol 1-adamantanic acid, 0.02 mmol of silver hexafluoroantimonate, 2mL of methanol, Reaction at 90 ° C for 12 hours; After completion of the reaction, the mixture was washed with ethyl acetate, concentrated under reduced pressure, and then chromatographed (silica gel 200-300 mesh, eluent: ethyl acetate / petroleum ether gradient elution, ratio: 0/100 to 100/0), dried Light yellow oil, The yield was 88% and E/Z = 20:1. |
88% | With silver hexafluoroantimonate; tris(acetonitrile)(η5-pentamethylcyclopentadienyl)rhodium(III) hexafluoroantimonate; 1-Adamantanecarboxylic acid In methanol at 90℃; for 12h; Inert atmosphere; diastereoselective reaction; | |
88% | With silver hexafluoroantimonate; tris(acetonitrile)(η5-pentamethylcyclopentadienyl)rhodium(III) hexafluoroantimonate; 1-Adamantanecarboxylic acid In methanol at 90℃; for 12h; Inert atmosphere; Sealed tube; Glovebox; regioselective reaction; |
87% | With silver hexafluoroantimonate; [ruthenium(II)(η6-1-methyl-4-isopropyl-benzene)(chloride)(μ-chloride)]2; mesitylenecarboxylic acid at 25℃; for 2h; Microwave irradiation; diastereoselective reaction; | |
70% | With silver hexafluoroantimonate; [ruthenium(II)(η6-1-methyl-4-isopropyl-benzene)(chloride)(μ-chloride)]2; mesitylenecarboxylic acid at 25℃; for 2h; Microwave irradiation; | 1 Example 1 Compound (E)-2-(4-(1-(2-pyrimidinyl)-7-indolinyl)-2-buten-1-yl)malonic acid diethyl ester The structural formula is: The preparation method is:In an air atmosphere,Add 0.2 mmol of N-pyrimidindolline compound to the microwave reaction tube,0.4mmol of ethylene cyclopropane compound,0.003mmol of [Ru (p-cymene) Cl2] 2,0.04mmol are trimethylbenzoic acid,0.02mmol of silver hexafluoroantimonate, microwave reaction at 25 ° C for 2 hours;After completion of the reaction, rinse with ethyl acetate.Chromatographic separation after concentration under reduced pressure (silica gel 200-300 mesh, eluent: ethyl acetate / petroleum ether gradient elution, ratio from 0/100 to 100/0),Dried to a pale yellow oil,Yield: 70%, E / Z = 20: 1. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
64% | With (5,5',6,6',7,7',8,8'-octahydro-1,1'-binaphthyl)-2,2'-diyl (R)-bis(1-phenylethyl)-phosphoramidite; bis(dibenzylideneacetone)-palladium(0) In toluene at 20℃; for 48h; Inert atmosphere; | 21 Example 21 Synthesis of optically active cyclopentane-3-imine 3u, the reaction formula of which is: Drying of the test tube is added Pd (dba)2 (5.8 Mg, 0 . 010 mmol), chiral asian phosphine amide ligand (7.2 mg, 0 . 012 mmol), replace the nitrogen after the air in the test tube, add 1 ml oxygen free of toluene, room temperature stirring 30 minutes later, to injected cyclized aza conjugated diene 1 a and vinyl cyclopropane dicarboxylic acid ethyl ester 2 b. The reaction mixture stirring at room temperature 48 h, the reaction mixture by adding 5 ml saturated ammonium chloride solution, ethyl acetate extraction reaction solution three times, each time the 10 ml, combined with the organic phase, dried by anhydrous sodium sulfate. Off the solvent after purification by column chromatography (petroleum ether: ethyl acetate=10:1), to obtain the cyclopentane -3 - imine 3 u. Yield 64%, colorless oily, 83% ee (IA, hexane: isopropanol=90:10, wavelength 254 nm, |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
91% | With tetrakis(triphenylphosphine) palladium(0) In tetrahydrofuran at 20℃; for 12h; Inert atmosphere; Schlenk technique; | 7 4.2.7.1. Diethyl 3-benzyl-3-vinyl-2,3-dihydrobenzo[e]pyrrolo[1,2-c][1,2,3]oxathiazine-1,1(10bH)-dicarboxylate 5,5-dioxide (15aa1 and 15aa2). Representative procedure A. General procedure: A flame-dried 10 mL flask equipped with a stir bar was charged with vinylcyclopropane 14a (32 mg, 0.13 mmol), the Pd(PPh3)4 (15 mg, 0.013 mmol) and the cyclic N-sulfonyl imine 4a (29 mg, 0.16 mmol). Then 1.5mL of dried THF was added, the yellow mixture was stirred at room temperature for 12 h. The reaction was quenched with 1M HCl (2 mL). The aqueous layer was extracted with CH2Cl2 (3*5 mL), the combined organic layers were washed with brine (5 mL), dried over MgSO4, filtered, and concentrated under vacuum. Expected compounds were isolated by silica gel chromatography using pentane (100 %) to pentane/AcOEt (7:3) as eluent. The solvent was removed under reduced pressure and afford two colorless oils (15aa1: 29 mg, 15aa2: 28 mg, combined yield: 90%); dr: 1:1 (determined by 1H NMR of the crude product). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
60% | Stage #1: Methyltriphenylphosphonium bromide With potassium hexamethylsilazane In tetrahydrofuran; toluene at 0℃; for 0.25h; Inert atmosphere; Schlenk technique; Stage #2: diethyl 2-formylcyclopropane-1,1-dicarboxylate In tetrahydrofuran; toluene at 0℃; for 0.5h; Inert atmosphere; Schlenk technique; | 5 4.2.6.5. Diethyl 2-vinylcyclopropane-1,1-dicarboxylate (14e) General procedure: KHMDS in toluene (0.5 M, 11.8 mL, 5.92 mmol) was added to an ice-cooled (0 °C) solution of methyltriphenylphosphonium bromide (2.35 g, 6.60 mmol) in THF (18 mL). After 15 min of stirring, a solution of the corresponding aldehyde (1.0 g, 3.30 mmol) in THF (10 mL plus 2*1 mL rinse) was added, and the mixture was stirred for 30 min at 0°C. The reaction was quenched with saturated aqueous NH4Cl (10 mL), and the resulting mixture was extracted with AcOEt (3*20 mL). The combined organic layers were washed with brine (15 mL), and dried over anhydrous MgSO4. Filtration and evaporation under vacuum furnished the crude product, which was purified by column chromatography using pentane/AcOEt (9.8:0.2 to 7.5:2.5) as eluent. The expected fractions were combined and the solvent was removed under vacuum to afford 450 mg of colorless oil (yield: 45%). The title compound was prepared according to the representative procedure 2 from the corresponding aldehyde (0.500 mg, 1.30 mmol) to give colorless oil (300 mg, yield: 60 %). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
83% | With [4,4′-bis(1,1-dimethylethyl)-2,2′-bipyridine-N1,N1′]bis{3,5-difluoro-2-[5-(trifluoromethyl)-2-pyridinyl-κN]phenyl-κC}iridium(III) hexafluorophosphate In water; 1,2-dichloro-ethane for 6h; Inert atmosphere; Sealed tube; Irradiation; | General procedure for the allylic trifluoromethylation of vinylcyclopropanes General procedure: To an oven dried borosilicate test tube equipped with a magnetic stir bar, was added VCP (0.15mmol, 1 eq.), CF3SO2Na (0.45 mmol, 3 eq.) and 2 mol% photocatalyst [Ir{dF(CF3)ppy}2(dtbpy)]PF6 (3.4mg, 0.02 equiv.). The reaction tube was vacuumed and backfilled with Argon (3 times) and sealed with a septum. To this, 3mL of DCE was added using a syringe, and the reaction tube placed ∼5 cm distance from the light setup. After 6 h, 10 mL of water was added and extracted with DCM (3×20mL). The combined organic layer was dried over Na2SO4 and solvent was removed under reduced pressure. The crude product was then purified by flash column chromatography on silica gel mesh 230-400 using hexane and EtOAc as eluent to give the trifluoromethylated product. |
79% | With 2,4,6-tris(4-methylphenyl)pyrylium tetrafluoroborate; acetic acid In 1,2-dichloro-ethane at 20℃; for 6h; Inert atmosphere; Irradiation; chemoselective reaction; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With ammonia at 120 - 130℃; for 16h; | ||
0.65 kg | With ammonium hydroxide at 110℃; for 19h; Large scale; | 1; 2; 4 1 kg of intermediate 1 and 6.5 L of formamide were pumped into the pressure reactor. Nitrogen replacement 2 times;Vacuum was again introduced into the liquid ammonia, the temperature was raised to 110 ° C, and the pressure in the kettle was maintained at 0.6-0.8 MPa for 19 hours.The reaction is completed, the temperature is lowered, and the pressure is released; the reaction solution is transferred to the enamel reactor;Concentrate under reduced pressure until the mass of the concentrated liquid is 1/2 of the mass of the reaction liquid at the end of the reaction;Discharge, transfer the material to the cold storage; crystallize for 8h; centrifuge, filter cake with isopropyl alcohol, centrifuge,Drying yields 0.65 kg of intermediate 2 (AX-2). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
93% | With tris-(dibenzylideneacetone)dipalladium(0); (-)-1(R),2(R)-bis<2'-(diphenylphosphino)benzamido>-1,2-diphenylethane; N-ethyl-N,N-diisopropylamine In acetonitrile at -20℃; for 10h; Inert atmosphere; enantioselective reaction; | General Procedure and Spectral Data of Products General procedure: To a solution of 0.13 mmol of 2-vinylcyclopropane-1,1-dicarboxylate 1 and 0.10 mmol of azlactone 2 in 1.0 mL of dried CH3CN was added 0.01 mmol of catalyst C5 at room temperature. The reaction was monitored by TLC. After the reaction was completed, the reaction mixture was concentrated under reduced pressure. The crude product was then purified by chromatography on silica gel. Elution with 6 : 1 PE-EtOAc. The enantiomeric purity of the product was determined by using HPLC and the d.r. value was determined by 1H NMR. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
84 % ee | With tris-(dibenzylideneacetone)dipalladium(0); (-)-1(R),2(R)-bis<2'-(diphenylphosphino)benzamido>-1,2-diphenylethane; triethylamine In acetonitrile at -20℃; for 10h; Inert atmosphere; Overall yield = 70 percent; enantioselective reaction; | General Procedure and Spectral Data of Products General procedure: To a solution of 0.13 mmol of 2-vinylcyclopropane-1,1-dicarboxylate 1 and 0.10 mmol of azlactone 2 in 1.0 mL of dried CH3CN was added 0.01 mmol of catalyst C5 at room temperature. The reaction was monitored by TLC. After the reaction was completed, the reaction mixture was concentrated under reduced pressure. The crude product was then purified by chromatography on silica gel. Elution with 6 : 1 PE-EtOAc. The enantiomeric purity of the product was determined by using HPLC and the d.r. value was determined by 1H NMR. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With tris-(dibenzylideneacetone)dipalladium(0); O,O′-(1,1′-dinaphthyl-2,2′-diyl)-N,N-di-iso-propylethylphosphoramidite; N-ethyl-N,N-diisopropylamine In acetonitrile at -20℃; for 10h; Inert atmosphere; | General Procedure and Spectral Data of Products General procedure: To a solution of 0.13 mmol of 2-vinylcyclopropane-1,1-dicarboxylate 1 and 0.10 mmol of azlactone 2 in 1.0 mL of dried CH3CN was added 0.01 mmol of catalyst C5 at room temperature. The reaction was monitored by TLC. After the reaction was completed, the reaction mixture was concentrated under reduced pressure. The crude product was then purified by chromatography on silica gel. Elution with 6 : 1 PE-EtOAc. The enantiomeric purity of the product was determined by using HPLC and the d.r. value was determined by 1H NMR. The racemic product 3 was obtained, using rac-D99 instead of L7. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
88 % ee | With tris-(dibenzylideneacetone)dipalladium(0); (-)-1(R),2(R)-bis<2'-(diphenylphosphino)benzamido>-1,2-diphenylethane; N-ethyl-N,N-diisopropylamine In acetonitrile at -20℃; for 10h; Inert atmosphere; Overall yield = 89 percent; enantioselective reaction; | General Procedure and Spectral Data of Products General procedure: To a solution of 0.13 mmol of 2-vinylcyclopropane-1,1-dicarboxylate 1 and 0.10 mmol of azlactone 2 in 1.0 mL of dried CH3CN was added 0.01 mmol of catalyst C5 at room temperature. The reaction was monitored by TLC. After the reaction was completed, the reaction mixture was concentrated under reduced pressure. The crude product was then purified by chromatography on silica gel. Elution with 6 : 1 PE-EtOAc. The enantiomeric purity of the product was determined by using HPLC and the d.r. value was determined by 1H NMR. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With tris-(dibenzylideneacetone)dipalladium(0); O,O′-(1,1′-dinaphthyl-2,2′-diyl)-N,N-di-iso-propylethylphosphoramidite; N-ethyl-N,N-diisopropylamine In acetonitrile at -20℃; for 10h; Inert atmosphere; | General Procedure and Spectral Data of Products General procedure: To a solution of 0.13 mmol of 2-vinylcyclopropane-1,1-dicarboxylate 1 and 0.10 mmol of azlactone 2 in 1.0 mL of dried CH3CN was added 0.01 mmol of catalyst C5 at room temperature. The reaction was monitored by TLC. After the reaction was completed, the reaction mixture was concentrated under reduced pressure. The crude product was then purified by chromatography on silica gel. Elution with 6 : 1 PE-EtOAc. The enantiomeric purity of the product was determined by using HPLC and the d.r. value was determined by 1H NMR. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
93% | With tris-(dibenzylideneacetone)dipalladium(0); (-)-1(R),2(R)-bis<2'-(diphenylphosphino)benzamido>-1,2-diphenylethane; N-ethyl-N,N-diisopropylamine In acetonitrile at -20℃; for 10h; Inert atmosphere; enantioselective reaction; | General Procedure and Spectral Data of Products General procedure: To a solution of 0.13 mmol of 2-vinylcyclopropane-1,1-dicarboxylate 1 and 0.10 mmol of azlactone 2 in 1.0 mL of dried CH3CN was added 0.01 mmol of catalyst C5 at room temperature. The reaction was monitored by TLC. After the reaction was completed, the reaction mixture was concentrated under reduced pressure. The crude product was then purified by chromatography on silica gel. Elution with 6 : 1 PE-EtOAc. The enantiomeric purity of the product was determined by using HPLC and the d.r. value was determined by 1H NMR. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With tris-(dibenzylideneacetone)dipalladium(0); O,O′-(1,1′-dinaphthyl-2,2′-diyl)-N,N-di-iso-propylethylphosphoramidite; N-ethyl-N,N-diisopropylamine In acetonitrile at -20℃; for 10h; Inert atmosphere; | General Procedure and Spectral Data of Products General procedure: To a solution of 0.13 mmol of 2-vinylcyclopropane-1,1-dicarboxylate 1 and 0.10 mmol of azlactone 2 in 1.0 mL of dried CH3CN was added 0.01 mmol of catalyst C5 at room temperature. The reaction was monitored by TLC. After the reaction was completed, the reaction mixture was concentrated under reduced pressure. The crude product was then purified by chromatography on silica gel. Elution with 6 : 1 PE-EtOAc. The enantiomeric purity of the product was determined by using HPLC and the d.r. value was determined by 1H NMR. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
89% | With tris-(dibenzylideneacetone)dipalladium(0); (-)-1(R),2(R)-bis<2'-(diphenylphosphino)benzamido>-1,2-diphenylethane; N-ethyl-N,N-diisopropylamine In acetonitrile at -20℃; for 10h; Inert atmosphere; enantioselective reaction; | General Procedure and Spectral Data of Products General procedure: To a solution of 0.13 mmol of 2-vinylcyclopropane-1,1-dicarboxylate 1 and 0.10 mmol of azlactone 2 in 1.0 mL of dried CH3CN was added 0.01 mmol of catalyst C5 at room temperature. The reaction was monitored by TLC. After the reaction was completed, the reaction mixture was concentrated under reduced pressure. The crude product was then purified by chromatography on silica gel. Elution with 6 : 1 PE-EtOAc. The enantiomeric purity of the product was determined by using HPLC and the d.r. value was determined by 1H NMR. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With tris-(dibenzylideneacetone)dipalladium(0); O,O′-(1,1′-dinaphthyl-2,2′-diyl)-N,N-di-iso-propylethylphosphoramidite; N-ethyl-N,N-diisopropylamine In acetonitrile at -20℃; for 10h; Inert atmosphere; | General Procedure and Spectral Data of Products General procedure: To a solution of 0.13 mmol of 2-vinylcyclopropane-1,1-dicarboxylate 1 and 0.10 mmol of azlactone 2 in 1.0 mL of dried CH3CN was added 0.01 mmol of catalyst C5 at room temperature. The reaction was monitored by TLC. After the reaction was completed, the reaction mixture was concentrated under reduced pressure. The crude product was then purified by chromatography on silica gel. Elution with 6 : 1 PE-EtOAc. The enantiomeric purity of the product was determined by using HPLC and the d.r. value was determined by 1H NMR. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90% | With tris-(dibenzylideneacetone)dipalladium(0); (-)-1(R),2(R)-bis<2'-(diphenylphosphino)benzamido>-1,2-diphenylethane; N-ethyl-N,N-diisopropylamine In acetonitrile at -20℃; for 10h; Inert atmosphere; enantioselective reaction; | General Procedure and Spectral Data of Products General procedure: To a solution of 0.13 mmol of 2-vinylcyclopropane-1,1-dicarboxylate 1 and 0.10 mmol of azlactone 2 in 1.0 mL of dried CH3CN was added 0.01 mmol of catalyst C5 at room temperature. The reaction was monitored by TLC. After the reaction was completed, the reaction mixture was concentrated under reduced pressure. The crude product was then purified by chromatography on silica gel. Elution with 6 : 1 PE-EtOAc. The enantiomeric purity of the product was determined by using HPLC and the d.r. value was determined by 1H NMR. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With tris-(dibenzylideneacetone)dipalladium(0); O,O′-(1,1′-dinaphthyl-2,2′-diyl)-N,N-di-iso-propylethylphosphoramidite; N-ethyl-N,N-diisopropylamine In acetonitrile at -20℃; for 10h; Inert atmosphere; | General Procedure and Spectral Data of Products General procedure: To a solution of 0.13 mmol of 2-vinylcyclopropane-1,1-dicarboxylate 1 and 0.10 mmol of azlactone 2 in 1.0 mL of dried CH3CN was added 0.01 mmol of catalyst C5 at room temperature. The reaction was monitored by TLC. After the reaction was completed, the reaction mixture was concentrated under reduced pressure. The crude product was then purified by chromatography on silica gel. Elution with 6 : 1 PE-EtOAc. The enantiomeric purity of the product was determined by using HPLC and the d.r. value was determined by 1H NMR. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
88% | With tris-(dibenzylideneacetone)dipalladium(0); (-)-1(R),2(R)-bis<2'-(diphenylphosphino)benzamido>-1,2-diphenylethane; N-ethyl-N,N-diisopropylamine In acetonitrile at -20℃; for 10h; Inert atmosphere; enantioselective reaction; | General Procedure and Spectral Data of Products General procedure: To a solution of 0.13 mmol of 2-vinylcyclopropane-1,1-dicarboxylate 1 and 0.10 mmol of azlactone 2 in 1.0 mL of dried CH3CN was added 0.01 mmol of catalyst C5 at room temperature. The reaction was monitored by TLC. After the reaction was completed, the reaction mixture was concentrated under reduced pressure. The crude product was then purified by chromatography on silica gel. Elution with 6 : 1 PE-EtOAc. The enantiomeric purity of the product was determined by using HPLC and the d.r. value was determined by 1H NMR. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With tris-(dibenzylideneacetone)dipalladium(0); O,O′-(1,1′-dinaphthyl-2,2′-diyl)-N,N-di-iso-propylethylphosphoramidite; N-ethyl-N,N-diisopropylamine In acetonitrile at -20℃; for 10h; Inert atmosphere; | General Procedure and Spectral Data of Products General procedure: To a solution of 0.13 mmol of 2-vinylcyclopropane-1,1-dicarboxylate 1 and 0.10 mmol of azlactone 2 in 1.0 mL of dried CH3CN was added 0.01 mmol of catalyst C5 at room temperature. The reaction was monitored by TLC. After the reaction was completed, the reaction mixture was concentrated under reduced pressure. The crude product was then purified by chromatography on silica gel. Elution with 6 : 1 PE-EtOAc. The enantiomeric purity of the product was determined by using HPLC and the d.r. value was determined by 1H NMR. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
77 % ee | With tris-(dibenzylideneacetone)dipalladium(0); (-)-1(R),2(R)-bis<2'-(diphenylphosphino)benzamido>-1,2-diphenylethane; N-ethyl-N,N-diisopropylamine In acetonitrile at -20℃; for 10h; Inert atmosphere; Overall yield = 85 percent; enantioselective reaction; | General Procedure and Spectral Data of Products General procedure: To a solution of 0.13 mmol of 2-vinylcyclopropane-1,1-dicarboxylate 1 and 0.10 mmol of azlactone 2 in 1.0 mL of dried CH3CN was added 0.01 mmol of catalyst C5 at room temperature. The reaction was monitored by TLC. After the reaction was completed, the reaction mixture was concentrated under reduced pressure. The crude product was then purified by chromatography on silica gel. Elution with 6 : 1 PE-EtOAc. The enantiomeric purity of the product was determined by using HPLC and the d.r. value was determined by 1H NMR. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With tris-(dibenzylideneacetone)dipalladium(0); O,O′-(1,1′-dinaphthyl-2,2′-diyl)-N,N-di-iso-propylethylphosphoramidite; N-ethyl-N,N-diisopropylamine In acetonitrile at -20℃; for 10h; Inert atmosphere; | General Procedure and Spectral Data of Products General procedure: To a solution of 0.13 mmol of 2-vinylcyclopropane-1,1-dicarboxylate 1 and 0.10 mmol of azlactone 2 in 1.0 mL of dried CH3CN was added 0.01 mmol of catalyst C5 at room temperature. The reaction was monitored by TLC. After the reaction was completed, the reaction mixture was concentrated under reduced pressure. The crude product was then purified by chromatography on silica gel. Elution with 6 : 1 PE-EtOAc. The enantiomeric purity of the product was determined by using HPLC and the d.r. value was determined by 1H NMR. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
88 % ee | With tris-(dibenzylideneacetone)dipalladium(0); (-)-1(R),2(R)-bis<2'-(diphenylphosphino)benzamido>-1,2-diphenylethane; N-ethyl-N,N-diisopropylamine In acetonitrile at -20℃; for 10h; Inert atmosphere; Overall yield = 84 percent; enantioselective reaction; | General Procedure and Spectral Data of Products General procedure: To a solution of 0.13 mmol of 2-vinylcyclopropane-1,1-dicarboxylate 1 and 0.10 mmol of azlactone 2 in 1.0 mL of dried CH3CN was added 0.01 mmol of catalyst C5 at room temperature. The reaction was monitored by TLC. After the reaction was completed, the reaction mixture was concentrated under reduced pressure. The crude product was then purified by chromatography on silica gel. Elution with 6 : 1 PE-EtOAc. The enantiomeric purity of the product was determined by using HPLC and the d.r. value was determined by 1H NMR. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With tris-(dibenzylideneacetone)dipalladium(0); O,O′-(1,1′-dinaphthyl-2,2′-diyl)-N,N-di-iso-propylethylphosphoramidite; N-ethyl-N,N-diisopropylamine In acetonitrile at -20℃; for 10h; Inert atmosphere; | General Procedure and Spectral Data of Products General procedure: To a solution of 0.13 mmol of 2-vinylcyclopropane-1,1-dicarboxylate 1 and 0.10 mmol of azlactone 2 in 1.0 mL of dried CH3CN was added 0.01 mmol of catalyst C5 at room temperature. The reaction was monitored by TLC. After the reaction was completed, the reaction mixture was concentrated under reduced pressure. The crude product was then purified by chromatography on silica gel. Elution with 6 : 1 PE-EtOAc. The enantiomeric purity of the product was determined by using HPLC and the d.r. value was determined by 1H NMR. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With tris-(dibenzylideneacetone)dipalladium(0); O,O′-(1,1′-dinaphthyl-2,2′-diyl)-N,N-di-iso-propylethylphosphoramidite; N-ethyl-N,N-diisopropylamine In acetonitrile at -20℃; for 10h; Inert atmosphere; | General Procedure and Spectral Data of Products General procedure: To a solution of 0.13 mmol of 2-vinylcyclopropane-1,1-dicarboxylate 1 and 0.10 mmol of azlactone 2 in 1.0 mL of dried CH3CN was added 0.01 mmol of catalyst C5 at room temperature. The reaction was monitored by TLC. After the reaction was completed, the reaction mixture was concentrated under reduced pressure. The crude product was then purified by chromatography on silica gel. Elution with 6 : 1 PE-EtOAc. The enantiomeric purity of the product was determined by using HPLC and the d.r. value was determined by 1H NMR. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90% | With tris-(dibenzylideneacetone)dipalladium(0); (-)-1(R),2(R)-bis<2'-(diphenylphosphino)benzamido>-1,2-diphenylethane; N-ethyl-N,N-diisopropylamine In acetonitrile at -20℃; for 10h; Inert atmosphere; enantioselective reaction; | General Procedure and Spectral Data of Products General procedure: To a solution of 0.13 mmol of 2-vinylcyclopropane-1,1-dicarboxylate 1 and 0.10 mmol of azlactone 2 in 1.0 mL of dried CH3CN was added 0.01 mmol of catalyst C5 at room temperature. The reaction was monitored by TLC. After the reaction was completed, the reaction mixture was concentrated under reduced pressure. The crude product was then purified by chromatography on silica gel. Elution with 6 : 1 PE-EtOAc. The enantiomeric purity of the product was determined by using HPLC and the d.r. value was determined by 1H NMR. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
89 % ee | With tris-(dibenzylideneacetone)dipalladium(0); (-)-1(R),2(R)-bis<2'-(diphenylphosphino)benzamido>-1,2-diphenylethane; N-ethyl-N,N-diisopropylamine In acetonitrile at -20℃; for 10h; Inert atmosphere; Overall yield = 54 percent; enantioselective reaction; | General Procedure and Spectral Data of Products General procedure: To a solution of 0.13 mmol of 2-vinylcyclopropane-1,1-dicarboxylate 1 and 0.10 mmol of azlactone 2 in 1.0 mL of dried CH3CN was added 0.01 mmol of catalyst C5 at room temperature. The reaction was monitored by TLC. After the reaction was completed, the reaction mixture was concentrated under reduced pressure. The crude product was then purified by chromatography on silica gel. Elution with 6 : 1 PE-EtOAc. The enantiomeric purity of the product was determined by using HPLC and the d.r. value was determined by 1H NMR. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With tris-(dibenzylideneacetone)dipalladium(0); O,O′-(1,1′-dinaphthyl-2,2′-diyl)-N,N-di-iso-propylethylphosphoramidite; N-ethyl-N,N-diisopropylamine In acetonitrile at -20℃; for 10h; Inert atmosphere; | General Procedure and Spectral Data of Products General procedure: To a solution of 0.13 mmol of 2-vinylcyclopropane-1,1-dicarboxylate 1 and 0.10 mmol of azlactone 2 in 1.0 mL of dried CH3CN was added 0.01 mmol of catalyst C5 at room temperature. The reaction was monitored by TLC. After the reaction was completed, the reaction mixture was concentrated under reduced pressure. The crude product was then purified by chromatography on silica gel. Elution with 6 : 1 PE-EtOAc. The enantiomeric purity of the product was determined by using HPLC and the d.r. value was determined by 1H NMR. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
91% | With tris-(dibenzylideneacetone)dipalladium(0); (-)-1(R),2(R)-bis<2'-(diphenylphosphino)benzamido>-1,2-diphenylethane; N-ethyl-N,N-diisopropylamine In acetonitrile at -20℃; for 10h; Inert atmosphere; enantioselective reaction; | General Procedure and Spectral Data of Products General procedure: To a solution of 0.13 mmol of 2-vinylcyclopropane-1,1-dicarboxylate 1 and 0.10 mmol of azlactone 2 in 1.0 mL of dried CH3CN was added 0.01 mmol of catalyst C5 at room temperature. The reaction was monitored by TLC. After the reaction was completed, the reaction mixture was concentrated under reduced pressure. The crude product was then purified by chromatography on silica gel. Elution with 6 : 1 PE-EtOAc. The enantiomeric purity of the product was determined by using HPLC and the d.r. value was determined by 1H NMR. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With tris-(dibenzylideneacetone)dipalladium(0); O,O′-(1,1′-dinaphthyl-2,2′-diyl)-N,N-di-iso-propylethylphosphoramidite; N-ethyl-N,N-diisopropylamine In acetonitrile at -20℃; for 10h; Inert atmosphere; | General Procedure and Spectral Data of Products General procedure: To a solution of 0.13 mmol of 2-vinylcyclopropane-1,1-dicarboxylate 1 and 0.10 mmol of azlactone 2 in 1.0 mL of dried CH3CN was added 0.01 mmol of catalyst C5 at room temperature. The reaction was monitored by TLC. After the reaction was completed, the reaction mixture was concentrated under reduced pressure. The crude product was then purified by chromatography on silica gel. Elution with 6 : 1 PE-EtOAc. The enantiomeric purity of the product was determined by using HPLC and the d.r. value was determined by 1H NMR. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
72% | With tris-(dibenzylideneacetone)dipalladium(0); (-)-1(R),2(R)-bis<2'-(diphenylphosphino)benzamido>-1,2-diphenylethane; N-ethyl-N,N-diisopropylamine In acetonitrile at -20℃; for 10h; Inert atmosphere; enantioselective reaction; | General Procedure and Spectral Data of Products General procedure: To a solution of 0.13 mmol of 2-vinylcyclopropane-1,1-dicarboxylate 1 and 0.10 mmol of azlactone 2 in 1.0 mL of dried CH3CN was added 0.01 mmol of catalyst C5 at room temperature. The reaction was monitored by TLC. After the reaction was completed, the reaction mixture was concentrated under reduced pressure. The crude product was then purified by chromatography on silica gel. Elution with 6 : 1 PE-EtOAc. The enantiomeric purity of the product was determined by using HPLC and the d.r. value was determined by 1H NMR. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With tris-(dibenzylideneacetone)dipalladium(0); O,O′-(1,1′-dinaphthyl-2,2′-diyl)-N,N-di-iso-propylethylphosphoramidite; N-ethyl-N,N-diisopropylamine In acetonitrile at -20℃; for 10h; Inert atmosphere; | General Procedure and Spectral Data of Products General procedure: To a solution of 0.13 mmol of 2-vinylcyclopropane-1,1-dicarboxylate 1 and 0.10 mmol of azlactone 2 in 1.0 mL of dried CH3CN was added 0.01 mmol of catalyst C5 at room temperature. The reaction was monitored by TLC. After the reaction was completed, the reaction mixture was concentrated under reduced pressure. The crude product was then purified by chromatography on silica gel. Elution with 6 : 1 PE-EtOAc. The enantiomeric purity of the product was determined by using HPLC and the d.r. value was determined by 1H NMR. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
77% | With tris-(dibenzylideneacetone)dipalladium(0); (-)-1(R),2(R)-bis<2'-(diphenylphosphino)benzamido>-1,2-diphenylethane; N-ethyl-N,N-diisopropylamine In acetonitrile at -20℃; for 10h; Inert atmosphere; enantioselective reaction; | General Procedure and Spectral Data of Products General procedure: To a solution of 0.13 mmol of 2-vinylcyclopropane-1,1-dicarboxylate 1 and 0.10 mmol of azlactone 2 in 1.0 mL of dried CH3CN was added 0.01 mmol of catalyst C5 at room temperature. The reaction was monitored by TLC. After the reaction was completed, the reaction mixture was concentrated under reduced pressure. The crude product was then purified by chromatography on silica gel. Elution with 6 : 1 PE-EtOAc. The enantiomeric purity of the product was determined by using HPLC and the d.r. value was determined by 1H NMR. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With tris-(dibenzylideneacetone)dipalladium(0); O,O′-(1,1′-dinaphthyl-2,2′-diyl)-N,N-di-iso-propylethylphosphoramidite; N-ethyl-N,N-diisopropylamine In acetonitrile at -20℃; for 10h; Inert atmosphere; | General Procedure and Spectral Data of Products General procedure: To a solution of 0.13 mmol of 2-vinylcyclopropane-1,1-dicarboxylate 1 and 0.10 mmol of azlactone 2 in 1.0 mL of dried CH3CN was added 0.01 mmol of catalyst C5 at room temperature. The reaction was monitored by TLC. After the reaction was completed, the reaction mixture was concentrated under reduced pressure. The crude product was then purified by chromatography on silica gel. Elution with 6 : 1 PE-EtOAc. The enantiomeric purity of the product was determined by using HPLC and the d.r. value was determined by 1H NMR. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
87 % ee | With tris-(dibenzylideneacetone)dipalladium(0); (-)-1(R),2(R)-bis<2'-(diphenylphosphino)benzamido>-1,2-diphenylethane; N-ethyl-N,N-diisopropylamine In acetonitrile at -20℃; for 10h; Inert atmosphere; Overall yield = 91 percent; enantioselective reaction; | General Procedure and Spectral Data of Products General procedure: To a solution of 0.13 mmol of 2-vinylcyclopropane-1,1-dicarboxylate 1 and 0.10 mmol of azlactone 2 in 1.0 mL of dried CH3CN was added 0.01 mmol of catalyst C5 at room temperature. The reaction was monitored by TLC. After the reaction was completed, the reaction mixture was concentrated under reduced pressure. The crude product was then purified by chromatography on silica gel. Elution with 6 : 1 PE-EtOAc. The enantiomeric purity of the product was determined by using HPLC and the d.r. value was determined by 1H NMR. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With tris-(dibenzylideneacetone)dipalladium(0); O,O′-(1,1′-dinaphthyl-2,2′-diyl)-N,N-di-iso-propylethylphosphoramidite; N-ethyl-N,N-diisopropylamine In acetonitrile at -20℃; for 10h; Inert atmosphere; | General Procedure and Spectral Data of Products General procedure: To a solution of 0.13 mmol of 2-vinylcyclopropane-1,1-dicarboxylate 1 and 0.10 mmol of azlactone 2 in 1.0 mL of dried CH3CN was added 0.01 mmol of catalyst C5 at room temperature. The reaction was monitored by TLC. After the reaction was completed, the reaction mixture was concentrated under reduced pressure. The crude product was then purified by chromatography on silica gel. Elution with 6 : 1 PE-EtOAc. The enantiomeric purity of the product was determined by using HPLC and the d.r. value was determined by 1H NMR. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
89 % ee | With tris-(dibenzylideneacetone)dipalladium(0); (-)-1(R),2(R)-bis<2'-(diphenylphosphino)benzamido>-1,2-diphenylethane; N-ethyl-N,N-diisopropylamine In acetonitrile at -20℃; for 10h; Inert atmosphere; Overall yield = 82 percent; enantioselective reaction; | General Procedure and Spectral Data of Products General procedure: To a solution of 0.13 mmol of 2-vinylcyclopropane-1,1-dicarboxylate 1 and 0.10 mmol of azlactone 2 in 1.0 mL of dried CH3CN was added 0.01 mmol of catalyst C5 at room temperature. The reaction was monitored by TLC. After the reaction was completed, the reaction mixture was concentrated under reduced pressure. The crude product was then purified by chromatography on silica gel. Elution with 6 : 1 PE-EtOAc. The enantiomeric purity of the product was determined by using HPLC and the d.r. value was determined by 1H NMR. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With tris-(dibenzylideneacetone)dipalladium(0); O,O′-(1,1′-dinaphthyl-2,2′-diyl)-N,N-di-iso-propylethylphosphoramidite; N-ethyl-N,N-diisopropylamine In acetonitrile at -20℃; for 10h; Inert atmosphere; | General Procedure and Spectral Data of Products General procedure: To a solution of 0.13 mmol of 2-vinylcyclopropane-1,1-dicarboxylate 1 and 0.10 mmol of azlactone 2 in 1.0 mL of dried CH3CN was added 0.01 mmol of catalyst C5 at room temperature. The reaction was monitored by TLC. After the reaction was completed, the reaction mixture was concentrated under reduced pressure. The crude product was then purified by chromatography on silica gel. Elution with 6 : 1 PE-EtOAc. The enantiomeric purity of the product was determined by using HPLC and the d.r. value was determined by 1H NMR. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
83% | With (4,4'-di-tert-butyl-2,2'-dipyridyl)-bis-(2-phenylpyridine(-1H))-iridium(III) hexafluorophosphate; toluene-4-sulfonic acid isopropylidenehydrazide; potassium carbonate In acetonitrile at 20℃; Irradiation; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
73% | With dichloro(pentamethylcyclopentadienyl)rhodium (III) dimer; copper diacetate; sodium acetate; silver(I) triflimide In 1,2-dichloro-ethane at 100℃; for 12h; Schlenk technique; | 2 Under an atmosphere of atmospheric pressure, in a 15mL Schlenk reaction tube was added N-nitrosyl compound 2b (15.4mg, 0.10mmol), vinylcyclopropane 3a (42.4mg, 0.20mmol), trivalent rhodium catalyst [Cp* RhCl2]2 (0.6mg), bistrifluoromethanesulfonimide silver salt (2.3mg), sodium acetate (4.9mg), copper acetate (12.0mg), 1,2-dichloroethane (DCE, 1mL) , React for 12 hours at a temperature of 100°C. After the reaction is over, it is cooled to room temperature, filtered through celite and concentrated to obtain a crude product. The crude product was separated by chromatography on a prepared silica gel plate. The selected developing solvent or eluent was petroleum ether and ethyl acetate with a volume ratio of 50:1. The product (E)-2-(3-(5- Ethyl fluoro-2-(methyl(nitroso)amino)phenyl)but-1-en-1-yl)dicarboxylate (1b), 26.7 mg, yield 73%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
64% | With dichloro(pentamethylcyclopentadienyl)rhodium (III) dimer; copper diacetate; sodium acetate; silver(I) triflimide In 1,2-dichloro-ethane at 100℃; for 12h; Schlenk technique; | 3 Under an atmosphere of atmospheric pressure, in a 15mL Schlenk reaction tube was added N-nitrosyl compound 2c (17.0 mg, 0.10 mmol), vinyl cyclopropane 3a (42.4 mg, 0.20 mmol), trivalent rhodium catalyst [Cp* RhCl2]2 (0.6mg), bistrifluoromethanesulfonimide silver salt (2.3mg), sodium acetate (4.9mg), copper acetate (12.0mg), 1,2-dichloroethane (DCE, 1mL) , React for 12 hours at a temperature of 100°C. After the reaction is over, it is cooled to room temperature, filtered through celite and concentrated to obtain a crude product. The crude product is separated by chromatography on a prepared silica gel plate. The selected developing solvent or eluent is petroleum ether and ethyl acetate in a volume ratio of 50:1, and the product (E)-2-(3-(5- Ethyl chloro-2-(methyl(nitroso)amino)phenyl)but-1-en-1-yl)dicarboxylate (1c), 24.0mg, yield 64%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
58% | With dichloro(pentamethylcyclopentadienyl)rhodium (III) dimer; copper diacetate; sodium acetate; silver(I) triflimide In 1,2-dichloro-ethane at 100℃; for 12h; Schlenk technique; | 4 In an atmosphere of atmospheric pressure, in a 15mL Schlenk reaction tube was added N-nitrosyl compound 2d (21.3mg, 0.10mmol), vinyl cyclopropane 3a (42.4mg, 0.20mmol), trivalent rhodium catalyst [Cp* RhCl2]2 (0.6mg), bistrifluoromethanesulfonimide silver salt (2.3mg), sodium acetate (4.9mg), copper acetate (12.0mg), 1,2-dichloroethane (DCE, 1mL) , React for 12 hours at a temperature of 100°C. After the reaction is over, it is cooled to room temperature, filtered through celite and concentrated to obtain a crude product. The crude product was separated by chromatography on a prepared silica gel plate. The selected developing solvent or eluent was petroleum ether and ethyl acetate with a volume ratio of 50:1. The product (E)-2-(3-(5- Ethyl bromo-2-(methyl(nitroso)amino)phenyl)but-1-en-1-yl)dicarboxylate (1d), 24.2mg, yield 58%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
67% | With dichloro(pentamethylcyclopentadienyl)rhodium (III) dimer; copper diacetate; sodium acetate; silver(I) triflimide In 1,2-dichloro-ethane at 100℃; for 12h; Schlenk technique; | 5 Under an atmosphere of atmospheric pressure, in a 15mL Schlenk reaction tube was added N-nitrosyl compound 2e (20.4mg, 0.10mmol), vinylcyclopropane 3a (42.4mg, 0.20mmol), trivalent rhodium catalyst [Cp* RhCl2]2 (0.6mg), bistrifluoromethanesulfonimide silver salt (2.3mg), sodium acetate (4.9mg), copper acetate (12.0mg), 1,2-dichloroethane (DCE, 1mL) , React for 12 hours at a temperature of 100°C. After the reaction is over, it is cooled to room temperature, filtered through celite and concentrated to obtain a crude product. The crude product was separated by chromatography on a prepared silica gel plate. The selected developing solvent or eluent was petroleum ether and ethyl acetate with a volume ratio of 50:1. The product (E)-2-(3-(5- Ethyl trifluoromethyl-2-(methyl(nitroso)amino)phenyl)but-1-en-1-yl)dicarboxylate (1e), 27.9 mg, yield 67%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
75% | With dichloro(pentamethylcyclopentadienyl)rhodium (III) dimer; copper diacetate; sodium acetate; silver(I) triflimide In 1,2-dichloro-ethane at 100℃; for 12h; Schlenk technique; | 6 Under an atmosphere of atmospheric pressure, in a 15mL Schlenk reaction tube was added N-nitrosyl compound 2f (18.1 mg, 0.10 mmol), vinyl cyclopropane 3a (42.4 mg, 0.20 mmol), trivalent rhodium catalyst [Cp* RhCl2]2 (0.6mg), bistrifluoromethanesulfonimide silver salt (2.3mg), sodium acetate (4.9mg), copper acetate (12.0mg), 1,2-dichloroethane (DCE, 1mL) , React for 12 hours at a temperature of 100°C. After the reaction is over, it is cooled to room temperature, filtered through celite and concentrated to obtain a crude product. The crude product was separated by chromatography on a prepared silica gel plate. The selected developing solvent or eluent was petroleum ether and ethyl acetate with a volume ratio of 50:1. The product (E)-2-(3-(5- Nitro-2-(methyl(nitroso)amino)phenyl)but-1-en-1-yl)ethyl dicarboxylate (1f), 31.0 mg, yield 75%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
71% | With dichloro(pentamethylcyclopentadienyl)rhodium (III) dimer; copper diacetate; sodium acetate; silver(I) triflimide In 1,2-dichloro-ethane at 100℃; for 12h; Schlenk technique; | 7 Under an atmosphere of atmospheric pressure, in a 15mL Schlenk reaction tube was added 2g (19.4mg, 0.20mmol) of N-nitrosyl compound to a 15mL Schlenk reaction tube, Me in 2g of N-nitrosyl compound is -CH3, vinylcyclopropane 3a( 42.4mg, 0.20mmol), trivalent rhodium catalyst [Cp*RhCl2]2 (0.6mg), bistrifluoromethanesulfonimide silver salt (2.3mg), sodium acetate (4.9mg), copper acetate (12.0mg) , 1,2-Dichloroethane (DCE, 1mL), react at 100°C for 12 hours. After the reaction is over, it is cooled to room temperature, filtered through celite and concentrated to obtain a crude product. The crude product was separated by chromatography on a prepared silica gel plate. The selected developing solvent or eluent was petroleum ether and ethyl acetate with a volume ratio of 50:1. The product (E)-2-(3-(5- Ethyl formate-2-(methyl(nitroso)amino)phenyl)but-1-en-1-yl)dicarboxylate (1 g), 28.8 mg, yield 71%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
70% | With dichloro(pentamethylcyclopentadienyl)rhodium (III) dimer; copper diacetate; sodium acetate; silver(I) triflimide In 1,2-dichloro-ethane at 100℃; for 12h; Schlenk technique; | 8 Under an atmosphere of atmospheric pressure, in a 15mL Schlenk reaction tube was added N-nitrosyl compound 2a (16.2mg, 0.10mmol), vinylcyclopropane 3a (42.4mg, 0.20mmol), trivalent rhodium catalyst [Cp* RhCl2]2 (0.6mg), bistrifluoromethanesulfonimide silver salt (2.3mg), sodium acetate (4.9mg), copper acetate (12.0mg), 1,2-dichloroethane (DCE, 1mL) , React for 12 hours at a temperature of 100°C. After the reaction is over, it is cooled to room temperature, filtered through celite and concentrated to obtain a crude product. The crude product was separated by chromatography on a prepared silica gel plate. The volume ratio of petroleum ether and ethyl acetate was 50:1 as the developing solvent or eluent. The product (E)-2-(3-(1- Nitroso-1,2,3,4-tetrahydroquinolin-8-yl)but-1-en-1-yl)ethyl dicarboxylate (1h), 26.2mg, yield 70%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
76% | With dichloro(pentamethylcyclopentadienyl)rhodium (III) dimer; copper diacetate; sodium acetate; silver(I) triflimide In 1,2-dichloro-ethane at 100℃; for 12h; Schlenk technique; | 1 Under an atmosphere of atmospheric pressure, in a 15mL Schlenk reaction tube was added N-nitrosyl compound 2a (13.6 mg, 0.10 mmol), vinyl cyclopropane 3a (42.4 mg, 0.20 mmol), trivalent rhodium catalyst [Cp* RhCl2]2 (0.6mg), bistrifluoromethanesulfonimide silver salt (2.3mg), sodium acetate (4.9mg), copper acetate (12.0mg), 1,2-dichloroethane (DCE, 1mL) , React for 12 hours at a temperature of 100°C. After the reaction is over, it is cooled to room temperature, filtered through celite and concentrated to obtain a crude product. The crude product was separated by chromatography on a prepared silica gel plate. The selected developing solvent or eluent was petroleum ether and ethyl acetate at a volume ratio of 50:1, and the product (E)-2-(3-(2- (Methyl(nitroso)amino)phenyl)but-1-en-1-yl)ethyl dicarboxylate (1a), 26.4mg, yield 76%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
72% | With copper(II) nitrate trihydrate; potassium iodide In 1,4-dioxane at 65℃; for 2h; Inert atmosphere; | 1 In a nitrogen atmosphere, 6.4 g of diethyl 2-vinylcyclopropane-1,1-dicarboxylate (30 mmol), 21.7 g of copper nitrate trihydrate (90 mmol), and 14.9 g of potassium iodide (90 mmol) were added to a 500 ml three-necked flask. ), 150 ml of 1,4-dioxane, heated to 65°C; followed the reaction by thin layer chromatography, and reacted for 2 hours until the raw material disappeared; After the reaction, the reaction system was cooled to room temperature, and the solvent was removed to obtain a crude product; using a developing solvent with a volume ratio of petroleum ether and ethyl acetate of 20:1, the crude product was directly separated and purified by column chromatography to obtain 5.6 Gram 2-(trans-2-nitrovinyl)cyclopropane-1,1-dicarboxylate diethyl ester, its structural formula is: the yield is 72%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
82.62% | With triphenylphosphine; Palladium(0) bis(dibenzylideneacetone) In tetrahydrofuran at 20℃; for 0.5h; Sealed tube; Inert atmosphere; | 1 Example 1 Combine (E)-N'-benzylidene-4-toluenesulfonylhydrazide (1 mmol, 1.0 equiv), bis(dibenzylideneacetone)palladium (0.05 mmol, 0.05 equiv) and triphenylphosphine (0.2 mmol, 0.2 equiv) to an oven-dried 25 mL tube with a standard grinding adapter and equipped with a stir bar. After sealing the tube with a rubber stopper and tape, the air inside the tube was evacuated with a vacuum pump and then injected with argon (repeated 3 times). Diethyl 2-vinylcyclopropane-1,1-dicarboxylate (1 mmol, 1 equiv) was then dissolved in THF (5 mL) and injected into the tube with a syringe. The reaction was stirred at high speed at room temperature. When the reaction was complete, the reaction mixture was quenched by adding saturated NaCl solution (10 mL) as detected by TCL. The reaction mixture was extracted with ethyl acetate (15 mL×3). The combined organic phases were dried over MgSO4, filtered and concentrated under reduced pressure on a rotary evaporator. The obtained residue was purified by column chromatography eluting with petroleum ether/EA=10:1 to give 1-((4-methylphenyl)sulfonamido)-2-phenyl-1,2,4,7 -Diethyl tetrahydro-3H-aza-3,3-dicarboxylate as a colorless gummy solid in 82.62% yield. |
Tags: 7686-78-4 synthesis path| 7686-78-4 SDS| 7686-78-4 COA| 7686-78-4 purity| 7686-78-4 application| 7686-78-4 NMR| 7686-78-4 COA| 7686-78-4 structure
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