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CAS No. : | 1603-79-8 | MDL No. : | MFCD00009120 |
Formula : | C10H10O3 | Boiling Point : | - |
Linear Structure Formula : | - | InChI Key : | QKLCQKPAECHXCQ-UHFFFAOYSA-N |
M.W : | 178.18 | Pubchem ID : | 15349 |
Synonyms : |
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Signal Word: | Warning | Class: | N/A |
Precautionary Statements: | P261-P305+P351+P338 | UN#: | N/A |
Hazard Statements: | H315-H319-H335 | 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 |
---|---|---|
98% | With hydrogen; In ethanol; at 20℃; under 3000.3 Torr; for 3h;Autoclave; | (3) Intermediate 1 (89g,475mmol) was added to the hydrogenation autoclave,Add ethanol (400g),Raney Nickel (2.2g),Nitrogen and hydrogen were replaced three times at room temperature,Pressurize hydrogen to 0.4MPa,Stir at room temperature for 3 hours.Properly supplement the hydrogen to maintain pressure during the process,Sampling for liquid chromatography analysis,After passing the test, the catalyst is recovered by filtration.The filter cake is washed with ethanol.Combine the filtrate and the washing liquid to carry out distillation to recover methanol.The inside of the kettle was a pale yellow viscous liquid (Intermediate 2) (90 g, yield 98%); |
93% | With Na(1+)*C12H33AlNO4Si2(1-); In tetrahydrofuran; toluene; at 0℃; for 1h;Inert atmosphere; | General procedure: A dry and argon-flushed flask, equipped with a magnetic stirring bar and septum, was charged with 4-acetylbenzaldehyde (1.0 mmol) and THF (10 mL). After cooling to 0 C, the modified Red-Al (0.5 M, 2.2 mL in THF) was added dropwise and the mixture was stirred for 1 h at 0 C. The reaction was quenched with 1 N aqueous HCl (10 mL) and the product was extracted with diethylether (10 mL). The organic layer was dried over anhydrous magnesium sulfate, the solvent was removed under reduced pressure and the crude residue was purified by column chromatography (SiO2, ethyl acetate/hexane, 1:5 v/v) to affording the desired alcohol (123 mg, 83% yield). |
91% | With methanol; benzaldehyde; 1,3-bis(mesityl)imidazolium chloride; triethylamine; at 25℃; for 5h;Inert atmosphere; | General procedure: To a mixture of imidazolium salt A (48 mg, 0.14 mmol) and distilled benzaldehyde (300 mg, 2.83 mmol) in MeOH (9.0 mL) was added triethylamine (21.5 mg, 0.21 mmol) followed by methyl 2-(2-chlorophenyl)-2-oxoacetate (842 mg, 4.24 mmol) under nitrogen atmosphere. The mixture was then stirred at 25 C for 5 h until benzaldehyde was consumed (monitored by TLC). After completion of the reaction the mixture was concentrated under vacuum and the residue was purified by flash chromatography on silica gel (230-400 mesh) using 10-15% EtOAc-hexane; spectral data of 4a: IR (film) 3467, 2954, 1741, 1222, 756 cm-1; 1H NMR (400 MHz, DMSO-d6): delta 7.43-7.53 (2H, m, CHarom), 7.32-7.39 (2H, m, CHarom), 6.36 (1H, d, J = 5.6 Hz, OH), 5.44 (1H, d, J = 6.0 Hz, C6H4CHOH); 3.62 (3H, s, OCH3); 13C NMR (100 MHz, CDCl3): delta 52.8, 70.1, 126.9, 128.6, 129.5, 129.6, 133.2, 135.9, 173.3; mass (ES) m/z 223 (M+Na)+; HRMS calculated for C9H10O3Cl [M+H]+ 201.0318. Found 201.0323. Compound 4f: IR (film) 3460, 2954, 1741, 1215, 772 cm-1; 1H NMR (400 MHz, CDCl3): delta 7.26-7.43 (4H, m, CHarom), 5.15 (1H, d, J = 5.6 Hz, C6H4CHOH), 3.77 (3H, s, OCH3), 3.55 (1H, d, J = 5.6 Hz, OH); 13C NMR (50 MHz, CDCl3): delta 53.1, 72.2, 124.7, 126.6, 128.5, 129.7, 134.4, 140.0, 173.4; mass (ES) m/z 223 (M+Na)+; HRMS calculated for C9H10O3Cl [M+H]+ 201.0318. Found 201.0327. |
85% | With potassium diisobutyl-tert-butoxyaluminum hydride; In tetrahydrofuran; at 0℃; for 1h;Inert atmosphere; | General procedure: A dry and argon-flushed flask, equipped with a magnetic stirring bar and a septum, was charged with dicarbonyl compound (1.0 mmol) and 10 mL THF. After cooling to 0C, PDBBA (1.3 mmol) was added dropwise and stirred for 1h at same temperature. The reaction was stopped by the aqueous 1N HCl (10mL) and extracted with diethyl ether (2×10mL). The combined organic layers were dried over MgSO4, filtered and concentrated under reduced pressure. Purification of the residue by column chromatography on silica gel afforded the desired product. |
In dichloromethane; | To a solution of ethyl benzoylformate (0.1106 g, 0.621 mmol) and the product of Example 3 (0.0123 g, 0.019 mmol) in dichloromethane (2 ml) was added an aqueous solution of sodium dithionite (85%; 0.430 g, 2.10 mmol) in 0.25M aqueous phosphate buffer (pH 7, 2.5 ml). The mixture was stirred vigorously under nitrogen in the dark at ambient temperature. After 20 h the yield of ethyl mandelate (as determined by gas chromatography) was 75%, which corresponds to 25 catalytic cycles. | |
The aqueous layer was replaced a second time by a fresh solution of sodium dithionite (85%; 0.397 g, 1.94 mmol) in 0.25M phosphate buffer (pH 7, 2.5 ml) and ethyl benzoylformate (0.0843 g, 0.474 mmol) was added. After a further 24 h the yield of ethyl mandelate was 85%, which corresponds to 63 catalytic cycles. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
89% | With 1,2-diphenyl-1,1,2,2-tetrahydroperoxyethane; hydrogen bromide; acetic acid; In water; at 40℃; for 0.333333h; | General procedure: A solution of alcohol (1 mmol), HOAc (0.1 mmol), HBr (0.5 mmol) and THPDPE (1 mmol) was stirred at 40 oC. After the completion of the reaction as followed by TLC, the mixture was quenched with Na2SO3 (3M, 1mL) and the products were extracted using CH3Cl (35 mL). For more purification, silica- packed column chromatography (hexane-EtOAc) was applied. Products were characterized on the basis of their melting points, elemental analysis and IR, 1H-NMR, and 13C-NMR spectral analysis. |
88% | With bismuth(III) bromide; dihydrogen peroxide; In water; at 70℃; for 0.166667h;Green chemistry; | General procedure: To a solution of the alcohol (1.0 mmol) and hydrogen peroxide(5.0 mmol, 30% aq) was added BiBr3 (10 mol%). The reactionmixture was stirred at 70 C for 10-40 min, and thereaction mixture was extracted with dichloromethane (2 × 5mL). The combined organic layers were washed with saturatedbrine (2 × 5 mL) and dried with anhydrous MgSO4. After evaporationof the solvent, the residue was purified by flash columnchromatography (SiO2; CH2Cl2-hexane, 3:2) to afford the purecarbonyl compound. |
70% | With benzeneseleninic acid; In water; acetone; at 40℃; for 6h; | 1mmol of theMandelic acid methyl ester0.05 mmolBenzene selenite(CAS: 6996-92-5)Mixed in2 mL of acetone,The reaction was stirred at a temperature of 60 C for 6 hours at a mixed system.After the reaction, the solvent was evaporated to dryness, separated by preparative thin layer chromatography,The oxidation product, methyl benzoylformate, was obtained in a yield of 73%. |
In zinc (II) bromide; | Radial chromatography (1 mm thick silica gel plate) gave unreacted ethyl benzoylformate (on elution with 20% diethyl ether/hexane) followed by <strong>[774-40-3]ethyl mandelate</strong> (on elution with 40% diethyl ether/hexane) (8.7 mg, 29%) which was pure by gas chromatography; 1 H n.m.r. 7.47-7.30 (5H, m, Ph), 5.17 (1H, s, CHOH), 4.32-4.12 (2H, m, OCH2 CH3, 3.63 (1H, bs, CHOH), 1.23 (3H, t, 3 JHH 7.1 Hz, OCH2 CH3): Identical to that of an authentic sample. In a similar reaction conducted in the presence of 1 equivalent of zinc (II) bromide instead of magnesium (II) perchlorate, the yield of <strong>[774-40-3]ethyl mandelate</strong> determined by gas chromatography was 35%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
99% | With tetrabutylammomium bromide; oxygen In water at 80℃; for 24h; | |
94% | With aluminum oxide; potassium permanganate; water In 1,2-dichloro-ethane for 161h; Ambient temperature; | |
86% | With 2,6-dimethylpyridine; N-hydroxyphthalimide; tetrabutylammonium perchlorate; oxygen In water; acetonitrile at 60℃; Electrochemical reaction; | 2.2. Procedures for synthesis of products 3 a-n General procedure: A 20 mL two-necked round-bottomed flask was charged with the substrate (0.50 mmol), NHPI (0.20 mmol), 2,6-lutidine (0.30 mmol) and n-Bu 4 NClO 4 (1.0 mmol). The flask was then equipped with a condenser, a carbon paper (1.0 cm ×1.0 cm) an- ode and a platinum net (1.0 cm ×1.0 cm) cathode, and flushed with oxygen. Acetonitrile (9.5 mL) and water (0.5 mL) were then added. The electrolysis was carried out at 60 °C using a constant current of 5 mA until cell voltage at 3.0 V. The reaction mixture was cooled to room temperature and concentrated under reduced pressure. The residue was chromatographed through silica gel elut- ing with ethyl acetate/petroleum ether (4:1) to give the desired product. |
82% | With tert.-butylhydroperoxide; C45H52CuN4O3 In decane; acetonitrile at 70℃; for 36h; Reflux; | |
72% | Stage #1: Ethyl 2-phenylethanoate With tert.-butylhydroperoxide; copper(II) oxide In water at 110℃; for 4.5h; Stage #2: With pyridine In water at 50℃; for 4h; | Typical procedure for the synthesis of α-ketoesters General procedure: Aryl acetate 1a (2.0 mmol, 1.0 equiv.), CuO (0.2 mmol, 0.1equiv.) and aq TBHP (6.0 mmol, 3.0 equiv.) were added to aflask connected to a reflux condenser. The flask was heated at 110 °C for 4.5 h and then cooled to room temperature.Pyridine (0.5 mL, 3.0 equiv.) was added and the mixture washeated to 50 °C and stirred for 4.0 h. Thereafter, an aqueoussolution of Na2S2O3 (0.5 mol L-1, 10.0 mL) was added, andthe mixture was extracted with EtOAc (×3). The organiclayers were combined, washed with brine, dried overanhydrous Na2SO4, filtered, concentrated and purified byflash column chromatography over silica gel (200-300 mesh) using petroleum ether/EtOAc (25:1) to afford thedesired compound 2a (172.3 mg, 53% yield) as a colourlessoil. |
31% | With iron(III) chloride; oxygen In N,N-dimethyl-formamide at 100℃; for 12h; | |
With air; cobalt(II) benzoate at 110 - 115℃; | ||
With selenium(IV) oxide at 150℃; | ||
81 % Chromat. | With oxygen; cobalt(II) acetate; 3-fluoro-N-hydroxyphthalimide In acetic acid at 40℃; for 24h; | |
82 % Chromat. | With dihydrogen peroxide In acetonitrile at 80℃; for 5h; | |
84 % Chromat. | With dihydrogen peroxide In water; acetonitrile at 80℃; for 5h; | |
Multi-step reaction with 3 steps 1: 4-acetamidobenzenesulfonyl azide; 1,8-diazabicyclo[5.4.0]undec-7-ene / acetonitrile / 0 - 25 °C / Inert atmosphere 2: Iron(III) nitrate nonahydrate / ethyl acetate / 3 h / 20 °C 3: triethylamine / ethyl acetate / 20 °C | ||
Multi-step reaction with 2 steps 1: 4-acetamidobenzenesulfonyl azide; 1,8-diazabicyclo[5.4.0]undec-7-ene / acetonitrile / 12 h / 20 °C / Inert atmosphere 2: oxygen; copper nanoparticles on activated carbon / 1,2-dichloro-ethane / 36 h / 30 °C / Schlenk technique | ||
Multi-step reaction with 2 steps 1: 4-acetamidobenzenesulfonyl azide; 1,8-diazabicyclo[5.4.0]undec-7-ene / acetonitrile / 0 - 23 °C / Inert atmosphere 2: acetic acid; tetra-(n-butyl)ammonium iodide / acetonitrile / 12 h / 20 °C / Electrochemical reaction; Green chemistry |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
72% | In tetrahydrofuran; diethyl ether at 0 - 20℃; for 3.75h; | A 250 mL round-bottom flask was charged with anhydrous THF (120 mL) at room temperature and then cooled to 0 0C with water/ice bath. Cyclohexylmagnesium chloride solution (2.0 M in ethyl ether) (56 mL, 112 mmol) was added. A solution of ethyl benzoylformate (14.89 g, 79.41 mmol) in THF (20 mL) was added dropwise over 30 minutes. More of THF (10 mL) was added to wash the addition funnel. The resulting mixture was stirred at 0 0C for 15 minutes, and then at room temperature for three hours. The reaction mixture was poured into saturated aqueous ammonium chloride (150 mL). Water (15 mL) was added. The mixture was concentrated to remove the organic solvents. The remaining solution was extracted with EtOAc (2 x 100 mL). The extraction was washed with brine, dried over sodium sulfate, concentrated to afford a slight green residue. The residue was purified with flash column chromatography on silica gel using 0-8% EtOAc/hexane (20 CV, 40 M column, biotage) to afford 14.955 g of product in 72 % yield. 1H-NMR (400 MHz, CDCl3). |
In diethyl ether | ||
In tetrahydrofuran at 0 - 20℃; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With hydrogen;RuBr2{(S)-2,2'-bis(diphenylphosphino)-1,1'-dinaphthyl};Product distribution / selectivity; | TABLE 2 below shows a comparison of the results of the hydrogenation of different substrates obtained on the one hand with the ruthenium complexes according to the invention and on the other hand with complexes of the type Ru-Binap, under the same operating conditions (temperature, pressure and solvent). [0235] TABLE 2 shows a comparison of the results obtained in TABLE 1 with the complexes according to the invention and the results obtained with the corresponding complexes in which the ligand (1) according to the invention has been replaced by the ligand BINAP. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With bis(1,5-cyclooctadiene)diiridium(I) dichloride; (R)-N-(3-methylpyridine-2-methyl)-7-bis-(3,5-di-tert-butylphenyl)phosphino-7?-amino-1,1?-spirodihydroindane; potassium tert-butylate; hydrogen; In ethanol; at 20℃; under 6080.41 - 7600.51 Torr; for 4h;Inert atmosphere; Sealed tube; | Example 11: Application of chiral spiro-pyridylamidophosphine ligand (R)-Ii (prepared in Example 9) in the asymmetric catalytic hydrogenation reaction of carbonyl compounds[0059] [0060] Under the protection of nitrogen atmosphere, 0.5 mg (0.74mumol) [Ir(COD)]Cl2, 1.2 mg (1.6mumol) (R)-Ii were added to the inner hydrogenation tube. Subsequently, 1 ml absolute ethyl alcohol was added and stirred for 1 h at room temperature. The inner reaction tube was placed into the hydrogenation reactor. After substitution by hydrogen, the reaction was stirred for 1 h at a hydrogen pressure of 1 atmosphere. The reactor was opened, and 7.5-150 mmol substrate (solid substrate, added after dissolved by ethanol) was added, followed by 0.05-25 mmol potassium tert-butoxide solution in ethanol (0.5 ml (0.1 mmol/mL)-25 ml (1 mmol/mL)) added with a syringe. The reactor was sealed, and hydrogen was filled to a pressure of 8-10 atm, and the reaction was stirred under the hydrogen pressure at room temperature for a while ranging from 10 minutes to 24 hours. After the hydrogenation was finished, the reaction solution was filtered through a short silica gel column to remove the catalyst, and the conversion rate and yield of the reaction were analyzed by gas chromatography or nuclear magnetic resonance (NMR); and the optical purity of the product was analyzed by gas chromatography or high performance liquid chromatography. The results of the hydrogenation experiments were listed in Table 1. | |
With tetraethylammonium iodide; water; Cinchonidin; In acetonitrile;Electrochemical reaction; | General procedure: The synthesis of Cu (Pt) NPs was performed as follows. 5 g of CuSO4*5H2O (2.07 g H2PtCl6*6H2O) was dissolved in 100 mL deionized water. 8 mL of ethylene glycol was then added into the solution. After 10 min of stirring, 50 mL of hydrazine hydrate solution (10%) was slowly added. The mixture was then stirred at 25 C for 4 h. Cu (Pt) was precipitated immediately. The precipitate was filtered, washed with 10 mL water and 10 mL anhydrous ethanol for 4 times each, and dried for 12 h under vacuum. The electrohydrogenation procedure is as follows. Cu NP powder was pressed into a coin and used as a cathode. Typical galvanostatic electrohydrogenation was conducted in a mixture of 50mM substrate, certain concentration of alkaloid and 0.1M tetraethylammonium iodide (TEAI) in a 20mL co-solvent (MeCN/H2O=9/1) in an undivided glass cell with a Cu NP cathode and sacrificial magnesium (Mg) anode. | |
With tetraethylammonium iodide; water; In acetonitrile; at 20℃;Electrochemical reaction; | General procedure: Typical electrochemical hydrogenation was conducted in a mixtureof 50 mM substrate, 0.1 M tetraethylammonium iodide (TEAI) in a20 mL co-solvent (MeCN/H2O = 9/1) in an undivided glass cell withan alkaloidCu cathode and sacrificialmagnesium(Mg) anode. The currentdensitywas 10mAcm-2 and the chargewas 300 C. The electrolytewas bubbled with high purity N2 throughout the electrolysis. All theprocedure was performed at room temperature. |
With Kluyveromyces polysporus alcohol dehydrogenase S237E mutant; isopropyl alcohol; NADPH; In aq. phosphate buffer; at 30℃;pH 7.0;Enzymatic reaction; | General procedure: Bioconversion was conducted with 20 mM 1a-10a,20 U·mL-1KpADH variants, 40 mM isopropanol in PBS buffer (pH 7.0,100 mM) in total volume of 2 mL at 30 C and 180 rpm overnight. Then,1 mL of the reaction mixture was withdrawn and extracted with ethylacetate. The organic phase was isolated by centrifugation and driedover anhydrous MgSO4. The conversion rate and enantioselectivity ofthe products were analyzed as described in supporting information. | |
With bis(acetylacetonato)palladium(II); hydrogen; Cinchonidin; In methanol; toluene;Autoclave; | General procedure: Hydrogenation reaction was performed in a Picoclave GlassUster cyclone 075 BUCHI autoclave. A solution of the precursor and the modifier: 0.0304 g (1×10-4 mol) of palladium acetylacetonate, ~10-4 mol of the modifier, 3 mL of toluene, and 19 mL of methanol was transferred to a 100 mL vessel being bubbled with hydrogen. The pale-yellow solution was stirred under hydrogen pressure of 5 atm during 30 min, then 0.5 mL of the substrate in 8 mL of methanol was added, and the ?zero sample? was withdrawn. The mixture of hydrogenation products was then analyzed each 30 or 60 min using the chromato-mass spectrometer. Configuration of the prevailing enantiomer was determined by comparison with the reference data [43]. | |
With diiodo(p-cymene)ruthenium(II) dimer; C17H13FeN; hydrogen; samarium(III) trifluoromethanesulfonate; In 1,4-dioxane; at 65℃; under 37503.8 Torr; for 48h; | The compound 10 (18 mg, 0 . 10 mmol), 5 a (2.9 mg, 0 . 01 mmol), Sm (OTf)3(12 Mg, 0 . 02 mmol), [Ru (p - cymene) I2]2(0.5 Mg, 0 . 0005 mmol) is dissolved in dioxane 2mL1, 4 -. Stir at room temperature 10 min after, the reaction system is transferred to the high-pressure reaction kettle and hydrogen is charged into the (50 bar). 65 C stirring for 48 h after, carefully release the remaining hydrogen, column chromatography to obtain compound 11, yield 55%, 35% ee. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
97% | With acrylic acid methyl ester; triphenylphosphine In ethanol at 20℃; for 9.5h; | |
92% | With triethylamine at 20℃; for 48h; | |
80% | With triethylamine at 20℃; for 48h; |
67% | With triethylamine at 20℃; for 48h; | 1.A Step-A: To a stirred solution of ethyl 2-oxo-2-phenylacetate (1.0 g, 5.612 mmol) in nitromethane (0.601 mL, 11.224 mmol) was added triethylamine (0.156 mL, 1.122 mmol). After being stirred at room temperature for 48h, the reaction mixture was concentrated under reduced pressure to dryness. The crude compound was purified by flash chromatography (Silica, 80 g Reveleris column; 0-50% ethyl acetate in hexane) to afford ethyl 2-hydroxy-3-nitro-2-phenylpropanoate as an off white solid (900 mg, 67%). 1H-NMR (500 MHz, DMSO-d6) δ = 7.55-7.54 (d, 2H), 7.41-7.34 (m, 3H), 6.80 (s, 1H), 5.59 - 5.57 (d, 1H), 4.83-4.80 (d, 1H), 4.21-4.15 (m, 2H), 1.19 - 1.17 (t, 3H). |
67% | With triethylamine at 20℃; for 48h; | 1.A Step-A: To a stirred solution of ethyl 2-oxo-2-phenylacetate (1.0 g, 5.612 mmol) in nitromethane (0.601 mL, 11.224 mmol) was added triethylamine (0.156 mL, 1.122 mmol). After being stirred at room temperature for 48h, the reaction mixture was concentrated under reduced pressure to dryness. The crude compound was purified by flash chromatography (Silica, 80 g Reveleris column; 0-50% ethyl acetate in hexane) to afford ethyl 2-hydroxy-3-nitro-2-phenylpropanoate as an off white solid (900 mg, 67%). 1H-NMR (500 MHz, DMSO-d6) δ = 7.55-7.54 (d, 2H), 7.41-7.34 (m, 3H), 6.80 (s, 1H), 5.59 - 5.57 (d, 1H), 4.83-4.80 (d, 1H), 4.21-4.15 (m, 2H), 1.19 - 1.17 (t, 3H). |
12% | Stage #1: nitromethane With anhydrous silver perchlorate In tetrahydrofuran at -10℃; for 0.5h; Inert atmosphere; Stage #2: phenylglyoxylic acid ethyl ester With 4-methyl-morpholine In tetrahydrofuran at -10℃; for 24h; Inert atmosphere; | |
With Amberlyst A-21 resin cooling; | ||
With copper(II) bis(trifluoromethanesulfonate); 2,2'-isopropylidenebis[(4S)-4-tert-butyl-2-oxazoline]; triethylamine at 20℃; | ||
With triethylamine at 20℃; for 72h; Inert atmosphere; | ||
With triethylamine at 20℃; | ||
With triethylamine at 20℃; Schlenk technique; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Stage #1: bromobenzene With magnesium In diethyl ether Stage #2: oxalic acid diethyl ester In diethyl ether at -78℃; | ||
Stage #1: bromobenzene With magnesium In tetrahydrofuran Stage #2: oxalic acid diethyl ester In tetrahydrofuran | ||
Stage #1: bromobenzene With iodine; magnesium In tetrahydrofuran Inert atmosphere; Stage #2: oxalic acid diethyl ester In tetrahydrofuran at -78 - 20℃; for 14h; Inert atmosphere; |
96 %Chromat. | Stage #1: bromobenzene With n-butyllithium In tetrahydrofuran; hexane at -60℃; for 0.00261667h; Flow reactor; Stage #2: oxalic acid diethyl ester In tetrahydrofuran; hexane at -60℃; for 0.000466667h; Flow reactor; Stage #3: With water; acetic acid In tetrahydrofuran; hexane | |
Stage #1: bromobenzene With magnesium In tetrahydrofuran Inert atmosphere; Reflux; Stage #2: oxalic acid diethyl ester In tetrahydrofuran at -78 - 10℃; for 1h; Inert atmosphere; | ||
Stage #1: bromobenzene With magnesium In tetrahydrofuran at 20℃; for 1h; Stage #2: oxalic acid diethyl ester In tetrahydrofuran at -78 - -10℃; for 1h; | ||
Stage #1: bromobenzene With magnesium In diethyl ether for 2h; Inert atmosphere; Schlenk technique; Reflux; Stage #2: oxalic acid diethyl ester In diethyl ether at -78℃; for 1h; Inert atmosphere; Schlenk technique; | ||
Stage #1: bromobenzene With magnesium In tetrahydrofuran at 20℃; for 0.5h; Inert atmosphere; Stage #2: oxalic acid diethyl ester In tetrahydrofuran at -78℃; for 1h; Inert atmosphere; | General Experimental Procedure for the Preparation of a-Ketoesters General procedure: Magnesium (5.5 mmol) was heated at reduced pressure for 5 min. THF (2 mL) was addedafter cooling to room temperature and aryl bromide (5.5 mmol) in THF (3 mL) was addeddropwise and stirred for 30 min. Grignard reagent was added dropwise to a solution of diethyloxalate (5 mmol) in THF (10 mL) at -78 oC. After 1 h at -78 oC, the mixture was warmed to room temperature, added with 2N HCl (10 mL). The aqueous layer was extracted with Et2Oand the combined organic layers were washed with brine and dried over Na2SO4. Afterremoval of the solvent, the crude product was purified by flash chromatography on silica gelto afford corresponding a-ketoester. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
85% | Stage #1: carbon tetrabromide With triphenylphosphine In dichloromethane at 0℃; for 0.5h; Inert atmosphere; Stage #2: phenylglyoxylic acid ethyl ester In dichloromethane at 0 - 20℃; for 12h; Inert atmosphere; | Ethyl 3,3-Dibromo-2-phenylpropenoate (10); General Procedurefor the Preparation of gem-Dibromoalkenes PPh3 (3.28 g, 12.5 mmol) was dissolved in anhyd CH2Cl2 (3 mL) in an oven-dried three-neck flask under argon. The mixture was cooled to 0 °C and CBr4 (2.07 g, 6.25 mmol) in solution in anhyd CH2Cl2 (2 mL) was added dropwise. The mixture was stirred at 0 °C for 30 min and a solution of ethyl mandelate (9, 0.559 g, 3.12 mmol) in anhyd CH2Cl2 (1.5 mL) was added dropwise. The mixture was allowed to warm to r.t. and stirred for 12 h or until completion was observed by TLC (Et2O/hexanes 10:90). Pentane (50 mL) was added to the mixture, which was stirred for 30 min. After filtration, the solvent was evaporated in vacuo and the crude product was purified by column chromatography (silica gel, Et2O/hexanes 10:90, Rf 0.43) yielding 1019b(0.880 g, 85%) as a colorless oil. IR (ATR, ZnSe): 1722, 1284, 1199, 1037, 1021, 794, 693 cm-1. 1H NMR (400 MHz, CDCl3): δ = 7.40-7.38 (m, 5 H), 4.27 (q, J = 7.2 Hz, 2H), 1.31 (t, J = 7.2 Hz, 3 H). 13C NMR (100 MHz, CDCl3): δ = 165.9, 141.6, 135.7, 129.0, 128.6, 128.2, 95.4, 62.3, 14.0. HRMS (ESI): m/z [M]+ calcd for C11H10O2Br: 334.9056; found: 334.9091. |
77% | With triphenylphosphine In dichloromethane at 0 - 20℃; for 15h; | |
58% | Stage #1: carbon tetrabromide With triphenylphosphine In dichloromethane at 0℃; for 0.5h; Stage #2: phenylglyoxylic acid ethyl ester In dichloromethane at 25℃; for 12h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
77% | With [Rh(BIPHEP)(NBD)]SbF6; triphenylacetic acid; hydrogen In 1,2-dichloro-ethane at 45℃; for 42h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
93% | With triphenylacetic acid; hydrogen; 2,2'-bis(diphenylphosphino)biphenyl In 1,2-dichloro-ethane at 80℃; for 3h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
93% | With 1,1'-bis-(diphenylphosphino)ferrocene; triphenylacetic acid; hydrogen In toluene at 60℃; for 1h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
94% | With 1,1'-bis-(diphenylphosphino)ferrocene; triphenylacetic acid; deuterium In toluene at 60℃; for 1.5h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
78% | Stage #1: 6-amino-5-nitroso-1-phenyl-1,3-dihydropyrimidine-2,4-dione With hydrogen In ethanol; water at 60℃; Stage #2: phenylglyoxylic acid ethyl ester for 0.5h; Heating / reflux; | 43 EXAMPLE 43; Preparation of 7-hydroxy-1,6-diphenyllumazine A suspension of 6-diamino-5-nitroso-1-phenyluracil (2.32 g, 0.01 moles) in H2O (50 ml) and EtOH (20 ml) was reduced by means of hydrogen in the presence of a platinum oxide catalyst in a shaking apparatus till about 450 ml of hydrogen was consumed. The mixture was heated up to 60 C., the catalyst filtered off and the filtrate treated with ethyl phenylglyoxylate (2.5 g, 0.014 mmoles) by heating under reflux for 30 minutes. The warm solution was acidified by HCl to pH 1 and the resulting precipitate was collected after cooling and re-crystallized from DMF, yielding 2.59 (78%) of a compound characterized as follows: m.p. 330 C.; UV (MeOH): 204 (4.54); [222 (4.37)]; 284 (4.17); 346 (4.25); 1H-NMR (DMSO): 11.81 (s, 1H); 8.01 (m, 2H); 7.50 (m, 8H). |
In ethanol; water; hydrogen | 43 Preparation of 7-hydroxy-1,6-diphenyllumazine EXAMPLE 43 Preparation of 7-hydroxy-1,6-diphenyllumazine A suspension of 6-diamino-5-nitroso-1-phenyluracil (2.32 g, 0.01 moles) in H2O (50 ml) and EtOH (20 ml) was reduced by means of hydrogen in the presence of a platinum oxide catalyst in a shaking apparatus till about 450 ml of hydrogen was consumed. The mixture was heated up to 60° C., the catalyst filtered off and the filtrate treated with ethyl phenylglyoxylate (2.5 g, 0.014 mmoles) by heating under reflux for 30 minutes. The warm solution was acidified by HCl to pH 1 and the resulting precipitate was collected after cooling and re-crystallized from DMF, yielding 2.59 (78%) of a compound characterized as follows: m.p. 330° C.; UV (MeOH): 204 (4.54); [222 (4.37)]; 284 (4.17); 346 (4.25); 1H-NMR (DMSO): 11.81 (s, 1H); 8.01 (m, 2H); 7.50 (m, 8H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
80% | With diphenyl(methyl)phosphine at 20℃; for 48h; |
Yield | Reaction Conditions | Operation in experiment |
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83% | With boric acid In 1,4-dioxane at 60℃; for 3h; |
Yield | Reaction Conditions | Operation in experiment |
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25% | With magnesium sulfate; acetic acid; In dichloromethane; at 20℃; for 20h; | A mixture of <strong>[30866-24-1]ethyl 3-hydrazino-3-oxopropionate</strong> (1.46 g, 10.0 mmol), ethyl benzoylformate (2.14 g, 12.0 mmol), acetic acid (0.5 mL, 8.3 mmol) and dichloromethane (10 mL) was stirred at room temperature with excess anhydrous magnesium sulfate for 20 h, then filtered and the cake washed with ethyl acetate. The filtrate was evaporated under reduced pressure, azeotroped 3 times with toluene and chromatographed (silica gel, 10-3- % ethyl acetate/hexane) to give the title compound (0.773 g, 25%). IH NMR (400 MHz, OMSO-d6) delta ppm 1.15 (t, J=7.07 Hz, 3 H) 1.30 (t, J=7.07 Hz, 3 H) 3.74 (s, 2 H) 4.08 (q, J=7.07 Hz, 2 H) 4.40 (q, J=7.18 Hz, 2 H) 7.42 - 7.49 (m, 3 H) 7.55 - 7.59 (m, 2 H) 11.57 (s, I H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
94% | With (diethylamino)sulfur trifluoride In ethanol; hexane; ethyl acetate | 2.6 6. 6. 2,2-Difluoro-2-phenylacetamide To a stirred 2.46 mL (15.5 mmol) of ethyl benzoylformate was added (diethylamino)sulfur trifluoride (5.0 g, 31 mmol) in one portion. After stirring for 4 hours under nitrogen, the reaction mixture was carefully poured into ice-water, extracted with dichloromethane (*3). The combined organic layers were washed with brine, dried over Na2SO4, and concentrated to give a pale amber oil. The oil was dissolved in anhydrous ethanol (25 mL) and saturated with gaseous ammonia for 0.5 hours in a pressure flask. The flask was then stopped and allowed to stand overnight. The solvent was removed to give a yellow solid that was crystallized by dissolving in 10 mL of warm ethyl acetate, and adding 30 mL of hot hexane. After cooling for several hours, the crystals were collected by filtration, washed with 1:4 ethyl acetate:hexane, and dried under high vacuum to give the title compound as a tan solid (2.5 g, 94%). 1H NMR (400 MHz, CDCl3) δ 7.61 (m, 2H), 7.47 (m, 3H), 6.40 (s(br), 1H), 6.34 (s(br), 1H). |
Multi-step reaction with 2 steps 1: 92 percent / (diethylamino)sulfur trifluoride / Ambient temperature 2: 89 percent / NH3 / 25 °C | ||
Stage #1: phenylglyoxylic acid ethyl ester With (bis-(2-methoxyethyl)amino)sulfur trufluoride In dichloromethane at 10 - 20℃; for 20h; Stage #2: With ammonia In methanol; dichloromethane at 60℃; for 2h; | 67.1-2 67Step 1. To a solution of ethyl benzoylformate (0.36 g, 2 mmol) in CH2Cl2 (10 mL) is added Deoxo- Fluor (1.1 mL, 6 mmol) at 1O0C. After 20 h at 200C, the mixture is quenched with water (10 mL), and poured into Chem-Elut with CH2Cl2 washing (10 mL). The filtrate is concentrated to give difluoro- phenyl-acetic acid ethyl ester, which is used for next step without further purification.Step 2. A solution of the above difluoro-phenyl-acetic acid ethyl ester and NH3 in MeOH (7 M, 10 mL) is heated to 6O0C for 2 h in a pressure tube. The mixture is cooled to room temperature, and concentrated to afford 2.2-difluoro-2-phenyl-acetamide (0.33 g). LCMS: Rx = 1.7 minutes; MS: 172 (M+H). |
Multi-step reaction with 2 steps 1: (bis-(2-methoxyethyl)amino)sulfur trufluoride / 20 h / 10 - 20 °C 2: ammonia / methanol / 2 h / 60 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With ammonium chloride; In tetrahydrofuran; ethyl acetate; | Step 1. To a stirred solution of <strong>[120363-13-5]tert-butyl 4-iodobenzoate</strong> (0.304 g, 1.0 mmol) in 10 mL THF at 40 C was added a solution of isopropylmagnesium bromide (1.05 ml, 1.05 mmol, 1M in THF) dropwise under argon. After stirring for 1 hour at -40 C., ethyl benzoylformate (0.175 ml, 1.1 mmol) was added dropwise and the cold bath allowed to warm to room temperature over a 40 min. period. The reaction was quenched by the addition of an aqueous solution of 20% ammonium chloride. The reaction mixture was extracted twice with ether, the combined organic layers washed with brine, dried over Na2SO4 and was evaporated to give an oil that was chromatographed on 10 g silica gel using a gradient elution from 0-40% EtOAc in Hexanes. Product containing fractions were combined and concentrated to give (0.078 g, 22%) ethyl (4-tert-butyloxycarbonylphenyl)(hydroxy)phenylacetate as a colorless oil. NMR, 400 MHz (CDCl3) 7.95 ppm (d, J=8.55 Hz, 2H), 7.52 ppm (d, J=8.55 Hz, 2H), 7.30-7.40 ppm (m, SH), 4.33 ppm (q, J=7.08 Hz, 2H), 4.29 ppm (s, OH, 1H), 1.59 ppm (s, 9H), 1.28ppm (t, J=7.08 Hz, 3H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
68% | With sodium hydride In tetrahydrofuran at 0℃; for 24h; | |
68% | Stage #1: phenylglyoxylic acid ethyl ester; 4-sulfamoylphenylacetamide With sodium hydride In tetrahydrofuran at 0℃; for 24h; Stage #2: With hydrogenchloride In tetrahydrofuran; water at 0℃; | 10 Example 10: Preparation of 3-(4-aminosulfonyrphenyl)-4-phenyl-lH-pyrrole-2.5dione (MCR-3015). To a solution of ethyl phenyloxoacetate(463 mg) and aminosulfonylphenylacetamide(355 mg) obtained in Example 9 dissolved in anhydrous THF(IO ml) at 0 0C was added NaH(60%, 133 mg), and the reaction mixture was stirred for 24 hours. Concentrated HC1(5 ml) was slowly added at O0C, and the reaction mixture was diluted with water and extracted with ethyl acetate three times. The organic phase was dried with anhydrous magnesium sulfate(MgSO4) and distilled under reduced pressure. The4 resulting residue was recrystallized with ethanol to give the target compound as a yellow solid(037 g, 68 %). [110] 1H NMR(400 MHz, DMSO-d6) δ 11.3(1H, s, -NH), 7.82(2H, d, J = 8.2 Hz, PhSO2NH2), 7.53(2H, d, J = 8.2 Hz, PhSO2NH2), 7.44(1H, s, PhSO2NH2), 7.44-7.36(5H, m, Ph): 13C NMR (IOO MHz, DMSO-d6) δ 171.3, 172.0, 144.5, 137.9, 135.4, 132.2, 130.2,129.8, 129.7, 129.6, 128.5, 128.3, 128.0, 125.9, 125.6, 62.0. |
With sodium hydride In tetrahydrofuran at 0℃; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
85% | With acetic acid In water at 20℃; for 24h; | |
81% | In water at 50℃; for 0.25h; | |
80% | With caesium carbonate In methanol at 78℃; for 0.5h; Inert atmosphere; | 1 2.2.1.1 Preparation of 3-Phenyl-1H-quinoxalin-2-one (3a) o-Phenelene diamine 1 (1 g, 9.25 mmol) and ethyl 2-oxo-2-phenylacetate 2a (2.47 g 13.8 mmol) in methanol was refluxed for 30 min at 78 °C. White solids were started forming during the course of the reaction under refluxing condition. After completion of the reaction the solid precipitate was filtered to get compound 3a in good yield (1.28 g, 80%). Similar procedure was followed for the synthesis of compounds 3b. |
With acetic acid In water at 20℃; for 24h; | ||
In ethanol | ||
In water at 50℃; for 0.25h; Inert atmosphere; | ||
With (R)-3,3'-bis(9-anthracenyl)-1,1'-binaphthyl phosphate In tetrahydrofuran at 50℃; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
40.3% | Stage #1: 2-amino-6-methoxy-3-nitro-benzoic acid methyl ester With hydrogen In ethyl acetate Stage #2: phenylglyoxylic acid ethyl ester In acetonitrile at 20℃; | 115.a 115(a) methyl 6-(methyloxy)-2-oxo-3-phenyl-1,2-dihydro-5-quinoxalinecarboxylate. To a solution of methyl 2-amino-6-(methyloxy)-3-nitrobenzoate (example 1(b), 4.0 g, 17.68 mmol) in ethyl acetate (25 mL) was added 10% palladium on charcoal (0.941 g, 0.884 mmol) followed by evacuation of the reaction vessel and purging with 50 psi of hydrogen. Following hydrogenation in the Parr Shaker overnight, the reaction mixture was filtered through Celite, washed through with ethyl acetate, and concentrated in vacuo. The resulting residue was dissolved in acetonitrile (25.00 mL), treated with ethyl oxo(phenyl)acetate (3.47 g, 19.45 mmol), and stirred at room temperature overnight. The resulting solid was filtered and dried in vacuo to obtain methyl 6-(methyloxy)-2-oxo-3-phenyl-1,2-dihydro-5-quinoxalinecarboxylate (2.21 g, 7.12 mmol, 40.3% yield) as a bright yellow solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 12.58 (br. s., 1H), 8.30 (d, J=1.5 Hz, 1H), 8.27-8.29 (m, 1H), 7.47-7.54 (m, 3H), 7.45 (d, J=9.1 Hz, 1H), 7.38 (d, J=9.1 Hz, 1H), 3.89 (s, 3H), 3.85 (s, 3H). MS (ES+) m/e 311 [M+H]+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
51.2% | Stage #1: 2-amino-6-methoxy-3-nitro-benzoic acid methyl ester With hydrogen In ethyl acetate Stage #2: phenylglyoxylic acid ethyl ester In acetonitrile Reflux; | 123.a 123(a) methyl 6-(methyloxy)-3-oxo-2-phenyl-3,4-dihydro-5-quinoxalinecarboxylate. To a solution of methyl 2-amino-6-(methyloxy)-3-nitrobenzoate (1.0 g, 4.42 mmol) in ethyl acetate (10.0 mL) was added 10% palladium on charcoal (0.235 g, 0.221 mmol) followed by evacuation of the reaction vessel and purging with 50 psi of hydrogen. Following hydrogenation in the Parr Shaker overnight, the reaction mixture was filtered through Celite, washed through with ethyl acetate, and concentrated in vacuo. The resulting residue was dissolved in acetonitrile (10.00 mL), treated with ethyl oxo(phenyl)acetate (0.867 g, 4.86 mmol), and stirred under reflux overnight. After cooling, the reaction mixture was filtered and washed with acetonitrile to obtain methyl 6-(methyloxy)-3-oxo-2-phenyl-3,4-dihydro-5-quinoxalinecarboxylate (0.703 g, 2.266 mmol, 51.2% yield) as a pale yellow solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 12.04 (br. s., 1H), 8.28 (d, J=2.0 Hz, 1H), 8.23-8.27 (m, 1H), 7.96 (d, J=9.1 Hz, 1H), 7.45-7.54 (m, 3H), 7.19 (d, J=9.1 Hz, 1H), 3.92 (s, 3H), 3.88 (s, 3H). MS (ES+) m/e 311 [M+H]+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
81% | With 1,3-bis(mesityl)imidazolium chloride; triethylamine In tetrahydrofuran at 25℃; for 6h; Inert atmosphere; Combinatorial reaction / High throughput screening (HTS); regioselective reaction; | 11 A typical procedure for hydroacylation reaction: General procedure: To a mixture of imidazolium salt A (48 mg, 0.14 mmol) and 2-thiophene-2-carbaldehyde (317 mg, 2.83 mmol) in THF (9.0 mL) was added triethylamine (21.5 mg, 0.21 mmol) followed by methyl 2-(2-chlorophenyl)-2-oxoacetate (842 mg, 4.24 mmol) under nitrogen atmosphere. The mixture was then stirred at 25 °C for 6 h until the aldehyde was consumed (monitored by TLC). After completion of the reaction the mixture was concentrated under vacuum and the residue was purified by flash chromatography on silica gel (230-400 mesh) using 5-10% EtOAc-hexane; spectral data of 3a: IR (film): 2949, 1750, 1719, 1253, 746 cm-1; 1H NMR (400 MHz, DMSO-d6): δ 8.04 (1H, m, CHthiophene), 7.91 (1H, m, CHthiophene), 7.44-7.62 (4H, m, C6H4), 7.25 (1H, m, CHthiophene), 6.57 (1H, s, CH), 3.73 (3H, s, OCH3); 13C NMR (50 MHz, DMSO-d6): δ 52.9, 71.3, 127.9, 128.6, 129.9, 130.0, 131.2, 131.3, 131.5, 133.1, 134.9, 135.1, 160.3, 167.8; mass (ES) m/z 328.4 (M+NH4)+; HRMS: calculated for C14H12O4SCl [M+H]+ 311.0145. Found 311.0153. Compound 3h: IR (film): 2952, 1751, 1708, 1289, 763 cm-1; 1HNMR (400 MHz, DMSO-d6); δ 7.82 (1H, d, J = 4.0 Hz, CHthiophene), 7.44-7.60 (4H, m, o-ClC6H4), 7.32 (1H, d, J = 4.0 Hz, CHthiophene), 6.67 (1H, s, CH), 3.73 (3H, s, OCH3); 13C NMR (50 MHz, DMSO-d6): δ 52.9, 71.5, 127.9, 128.9, 129.7, 129.9, 130.2, 131.2, 131.4, 133.2, 135.0, 159.2, 167.6; mass (ES) m/z 362 (M+NH4)+; HRMS calculated for C14H11O4SCl2 [M+H]+ 344.9755. Found 344.9753. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
72% | With Zr(OtBu)2-[(R)-3,3'-(3,5-bis(trifluoromethyl)phenyl)2-BINOL] In toluene at 20℃; for 20h; Inert atmosphere; optical yield given as %ee; enantioselective reaction; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
83.2% | Weigh 215 mg of methyltriphenylphosphonium bromide,Place in a 25 mL three-necked flask and add 5 mL of anhydrous tetrahydrofuran.Under nitrogen protection,Add 1 M bis(trimethylsilyl)amino potassium tetrahydrofuran 0.5 mL at -78 C.After reacting at -78 C for 1 hour,After moving to room temperature and continuing the reaction at room temperature for 1 hour,Move again to -78 C,Add at -78 CEthyl benzophenonecarboxylate 566mg,After reacting at -78 C for 1 hour, the reaction was again carried out to room temperature for 3 hours.Add 2 mL of 2M hydrochloric acid, extract three times with ethyl acetate, dry over anhydrous sodium sulfate, and isolate by column chromatography to obtain a pale yellow oily liquid, yield 83.2% |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
220 mg | With tert.-butylhydroperoxide; palladium diacetate; In tetrahydrofuran; at 110℃; for 96h;Sealed tube; | Step 1): Compound 23 (500 mg, 2.64 mmol), compound 24 (704 mg, 3.96 mmol), t-butyl hydroperoxide (0.72 mL, 3.96 mmol), palladium acetate (29.6 mg, 0.132 mmol) and Anhydrous tetrahydrofuran (10 mL) was sequentially added to the sealed tube, and the mixed system was heated to 110 C and stirred for 96 hours.It was concentrated under reduced pressure, and the residue was purified by silica gel chromatography.Eluted with petroleum ether / ethyl acetate = 5: 1,Concentration gave compound 25 (220 mg) as a yellow oil. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90% | With oxygen In tetrahydrofuran at 20℃; for 24h; Irradiation; | General remarks General procedure: alcohols0.6 mmolbenzoylacetonitrile0.4 mmolTHF2 mLwere added to grass tube. The reaction mixture was irradiated byone halogen tungsten lamp (500W) for 24 h accompanied with a fan beingsufficient to allow reaction temperature down to room temperature. After thereaction was completed (monitored by TLC), the reaction liquid was purifiedby chromatography on silica gel (20:1 petroleum ether/EtOAc) to give theproduct 3a-3s. |
86% | With [bis(acetoxy)iodo]benzene In dichloromethane for 0.5h; Reflux; | General procedure A for a-keto esters 3a-o General procedure: β-Oxo-benzenepropanenitrile 1(1.0 mmol),PIDA (2.2 mmol) were dissolved in EtOH (8 mL) and stirred under refluxing for 0.5h. After the reaction was completed (monitored by TLC), thereaction mixture was concentrated under vacuum. The residue was purified by chromatographyon silica gel (20:1 petroleum ether/EtOAc) to give the product 3a-o .Thesolvent for the synthesis of 3o was MeOH. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
82% | With titanium(IV) tetraethanolate In tetrahydrofuran at 60℃; for 6h; | 3 4.4 General procedure for the preparation of ketimines 3c-e General procedure: To a solution of the corresponding ketoester 2c-d (5.5mmol) in dry THF (15mL) was added (SS)-tert-butanesulfinamide (1, 0.605g, 5.0mmol) and titanium tetraethoxide (2.280g, 2.095mL, 10.0mmol). The resulting mixture was stirred at 60°C for 6h, and after that quenched with brine (4.0mL), and diluted with ethyl acetate (3×10mL). The resulting suspension was filtered through a short plug of Celite and concentrated (15Torr). The residue was purified by column chromatography (hexane/ethyl acetate) to yield pure compounds 3c-e. Yields for these compounds 3 are given on Scheme 2. Physical and spectroscopic data follow. |
72% | With titanium(IV) isopropylate In tetrahydrofuran at 65℃; for 6h; Inert atmosphere; | |
68.9% | With titanium(IV) tetraethanolate In tetrahydrofuran at 65℃; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
13% | [0521j Step A: Preparation of ethyl 2-( 1 ,6-dimethyl- 1H-benzo [dlimidazol-2-yl)-2- hydroxy-2-phenylacetate: To a solution of 1 ,6-dimethylbenzimidazole (0.35 g, 2.39 mmol)THF (5 mL) was added n-BuLi (2.5 M in hexane, 1.0 mL, 2.5 mmol) at -78 C. The reaction mixture was stirred at -78 C for 30 minutes. Ethyl 2-oxo-2-phenyl-acetate (0.47 g, 2.63 mmol) in THF (5 mL) was added at -78 C. After the addition, the reaction mixture was warmed to ambient temperature and stirred at ambient temperature for 1 hour. Saturated aqueous ammonium chloride solution (10 mL) and ethyl acetate (20 mL) were added. The organic layer was separated, washed with brine, dried (sodium sulfate), filtered and concentrated under reduced pressure. The residue obtained was purified by flash chromatography on silica gel with 3:1 hexane/ethyl acetate to give ethyl 2-( 1,6- dimethylbenzimidazol-2-yl)-2-hydroxy-2-phenyl-acetate (0.10 g, 13%) as oil. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95% | With N,N,N,N,N,N-hexamethylphosphoric triamide In dichloromethane at -78 - 20℃; for 22h; | 1 In a 25 mL Schlenk flask with magnetic stir bar,Followed by the addition of 1.5 mL of dichloromethane,(0.21 mmol) of the α, β-unsaturated oxindole compound (R3 = H, R4 = Ph, R5 = Bn) in 36 mg (0.20 mmol) of α-ketoester (R1 = Ph, R2 = OEt) The reaction mixture was stirred at -78 ° C for 10 minutes,Followed by 0.5 mLDichloromethane diluted hexamethylphosphoric triamide38 [mu] L (0.21 mmol),Concentration of 0.42mol / L,Was added dropwise to the above reaction mixture over 5 minutes,Upon completion of the addition, the reaction was gradually warmed to room temperature,Stirring was continued for 22 hours,After completion of the reaction, the solvent was removed by rotary evaporation,The crude product was purified by 200-300 mesh silica gel column chromatography to obtain oxindole spirocyclopropane target compound. The eluent was petroleum ether (boiling range: 60-90 degrees Celsius): ethyl acetate, the volume ratio was 10: 1 ~ 5: 1, gradient washing; get pure white solid 95mg, 95% yield. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
99% | With N,N,N,N,N,N-hexamethylphosphoric triamide In dichloromethane at -78 - 20℃; for 24h; | 2 The synthesis steps of the embodiment 1 is basically the same, the difference-listed as follows:The α, β-unsaturated oxindole compound R3= 5-Me, R4=Ph, R5=Bn, the amount of 75 mg (0.21mmol), room temperature and the reaction time is 24 hours, to obtain strawcoloured solid pure product 102 mg, yield is 99%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
96% | With N,N,N,N,N,N-hexamethylphosphoric triamide In dichloromethane at -78 - 20℃; for 21h; | 3 The synthesis steps of the embodiment 1 is basically the same, the difference-listed as follows:The α, β-unsaturated oxindole compound R3= 5-MeO, R4=Ph, R5=Bn, consumption is 77 mg (0.21mmol), the reaction mixture at -70 ° C stirring 15 minutes, phosphorus reagent in 15 minutes of the completion of the dropping, the reaction time at room temperature for 21 hours, to obtain white solid pure product 102 mg, yield is 96%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
99% | With N,N,N,N,N,N-hexamethylphosphoric triamide In toluene at -78 - 20℃; for 5h; | 5 The synthesis steps of the embodiment 1 is basically the same, the difference-listed as follows:The α, β-unsaturated oxindole compound R3= 6-Br, R4=Ph, R5=Bn, consumption is 88 mg (0.21mmol), the reaction solvent is toluene, phosphorus reagent using phosphorous acid triethyl ester 36 μ L (0.21mmol), room temperature and the reaction time is 5 hours, to obtain strawcoloured solid pure product 115 mg, yield is 99%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
85% | With triethyl phosphite In dichloromethane at -78 - 20℃; for 21h; | 6 The synthesis steps of the embodiment 1 is basically the same, the difference-listed as follows:The α, β-unsaturated oxindole compound R3=H, R4= 4-MeOPh, R5=Bn, consumption is 81 mg (0.22mmol), the amount of diethyl triamine six methyl Asia phosphine acid radical 40 μ L (0.22mmol), concentration is 0.44mol/L, room temperature and the reaction time is 24 hours, to obtain strawcoloured solid pure product 90 mg, yield is 85%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
99% | With phosphorous acid trimethyl ester In dichloromethane at -78 - 20℃; for 21h; | 7 The synthesis steps of the embodiment 1 is basically the same, the difference-listed as follows:The α, β-unsaturated oxindole compound R3=H, R4= 3-pyridyl, R5=Bn, consumption is 72 mg (0.21mmol), phosphorus reagent using trimethyl phosphite 25 μ L (0.21mmol), reaction time at room temperature for 21 hours, to obtain strawcoloured solid pure product 99 mg, yield is 99%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95% | With N,N,N,N,N,N-hexamethylphosphoric triamide In dichloromethane at -68 - 20℃; for 20h; | 8 The synthesis steps of the embodiment 1 is basically the same, the difference-listed as follows:The α, β-unsaturated oxindole compound R3=H, R4=Ph, R5=Me, the amount of 56 mg (0.21mmol), the reaction solvent is diethyl ether, the reaction mixture at -68 ° C stirring 15 minutes, the reaction time at room temperature for 20 hours, to obtain strawcoloured solid pure product 81 mg, yield is 95%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
41% | With caesium carbonate; In dimethyl amine; at 20℃;Glovebox; | In the glove box,Cs2CO3 (0.6 mmol) and ethyl benzoylformate (0.2 mmol) were weighed into 25 mL of the reaction tube,Measure the amount of DMA (1 mL) into the reaction tube.A bromodifluoromethylphosphonium salt (0.6 mmol) was weighed,Treated with DMA (2 mL)Inhalation into the syringe.Stirred at room temperature,A DMA solution of bromodifluoromethylphosphonium salt was injected into the reaction tube at a rate of 0.5 mL / h with a syringe pump.After the injection, the reaction is over. The solution in the reaction tube was transferred to a separatory funnel, 15 mL of water was added, extracted three times with dichloromethane (10 mL x 3), and the organic phases were combined and washed three times with water (10 mL x 3). The final obtained organic phase was dried over anhydrous sodium sulfate, and the solid was filtered off, the solvent removed by rotary evaporation, on a silica gel column with n-pentane and ethyl acetate as eluent, to give the final isolated product difluoromethyl, yield 41%, purity> 99.9% (NMR purity). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95% | With tert.-butylhydroperoxide; iodine; sodium carbonate In 1,2-dichloro-ethane at 60℃; for 7h; | General experimental procedure for the synthesis of α-ketoesters General procedure: To a mixture of trifluoromethyl β-diketones 1 (0.5 mmol, 1.0 equiv), alcohols 2 (1.5 mmol, 3.0 equiv), I2S2(0.55 mmol, 1.1 equiv), tert-butyl hydroperoxide (1.25 mmol, 2.5 equiv) and Na2CO3 (0.5 mmol, 1.0 equiv) wasadded 1,2-dichloroethane (1.5 mL) at room temperature. The reaction mixture was then stirred at 60 oC for 7.0 h.When the reaction was completed (monitored by TLC), the reaction was quenched with 2 mL of saturated NH4Claqueous and 4 mL of saturated Na2S2O3 aqueous. After extraction with EtOAc and drying with Na2SO4, theorganic layer was concentrated under reduced pressure and the residue was purified by column chromatography onsilica gel using hexanes/EtOAc (100:1 to 50:1) as eluent to afford the desired products 3. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
97.2% | With [pentamethylcyclopentadienyl*Ir(N-phenyl-2-pyridinecarboxamidate)Cl]; ammonium formate In methanol at 37℃; for 6h; chemoselective reaction; | General Procedure for Reductive Amination of α-Ketoacids General procedure: α-Ketoacid (0.2 mmol) and Ir1 (1 mol%) were added to a 1.5-dram vial equipped with amagnetic stir bar in methanol (1 mL). Solid HCOONH4 (2 mmol, 10 equiv.) was added to thevial and the solution was stirred at 37 °C for 6 h. The precipitate was filtered, washed with asmall amount of cold methanol, and dried under vacuum to give the desired α-amino acid. (±)-2-Amino-2-phenylacetic acid (10g)This amino acid was synthesized from 2-oxo-2-phenylacetic acid (9g) according to the general procedure above. The product was isolated as white solid in 97% yield.1H NMR (500 MHz, DMSO-d6 + 1 drop of HCl): δ 8.89 (s, 3H), 7.50 - 7.39 (m,5H), 5.02 (s, 1H) ppm; 13C NMR (126 MHz, DMSO-d6 + 1 drop of HCl): δ 170.0, 133.4, 129.8,129.4, 128.5, 56.0 ppm. The characterization data for this compound matched those reported. |
80 %Chromat. | With ammonia; hydrogen In tetrahydrofuran at 120℃; for 24h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
82.1% | With lanthanum(lll) triflate; In methanol;Inert atmosphere; | (2) Under nitrogen atmosphere, add o-nitrobenzenesulfonylhydrazide (2.17 g, 10 mmol) to the reaction flask in this order,The catalyst lanthanum triflate (117 mg, 0.2 mmol) and 20 ml of methanol as solvent,Then ethyl benzoyl formate (1.96 g, 11 mmol) was added slowly to the system, and as the reaction progressed, the system was gradually solid-precipitated. 20 mL of ether was added to keep itGood mixing, the reaction was detected by TLC o-nitrobenzene sulfonyl hydrazide disappeared. Filtration, recrystallization and drying in vacuo afforded a yellow solidO-Nitrobenzenesulfonylhydrazone (3.10 g, yield: 82.1%) of ethyl benzoylformate |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
85% | Stage #1: phenylglyoxylic acid ethyl ester; 1,3-diphenyl-2,3-diazaprop-2-en-1-one In dichloromethane at -78℃; for 0.25h; Schlenk technique; Stage #2: With N,N,N,N,N,N-hexamethylphosphoric triamide In dichloromethane at 20℃; for 8h; | 1 Example 1Synthesis of 2,2,5-trisubstituted 1,3,4-oxadiazole derivatives,In the general formula I R1 = Ph, R2 = Ph, R3 = Ph, R4 = OEt. In a 25 mL schlenk flask with a magnetic stir bar,Followed by adding 1.5mL dichloromethane,N-acyl bisazepines(R1 = Ph, R2 = Ph) (84 mg, 0.40 mmol),And a-keto ester (R3 = Ph, R4 = OEt) (36 mg, 0.2 mmol),The resulting reaction mixture was stirred at -78 ° C for 15 minutes,It will be 0.5 mL later55 μL (0.3 mmol) of hexamethylphosphoric triamide diluted with dichloromethane at a concentration of 0.6 mol / L,Was added dropwise to the above reaction mixture over 10 minutes,After the addition was completed, the reaction was slowly warmed to room temperature and stirred for 8 hours,After completion of the reaction, the solvent was removed by rotary evaporation,The crude product was purified by silica gel column chromatography (200-300 mesh) to obtain the target compound of oxadiazole with petroleum ether (boiling range 60-90 ° C):Ethyl acetate in a volume ratio of 10: 1; pure orange oil obtained 63mg,The yield is 85%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
77% | With acetic acid; In ethanol; for 3h;Inert atmosphere; Reflux; | General procedure: Photochromic hydrazone switches are directly synthesized from the corresponding alpha -keto ester and phenylhydrazine derivatives using a modified reported procedures. [Qian, H.; Aprahamian, I. Chem. Commun. 2015, 51, 11158-11161.] Phenylhydrazine derivatives (1 mmol) and catalytic amount of acetic acid (HO Ac) are added to an ethanol solution of alpha -keto ester (1 equiv.) derivatives under N2 atmosphere. The resulting mixture is stirred and refluxed for 3 hrs, and then cooled to room temperature. Ethanol is removed under vacuum. The crude residue is redissolved in methylene chloride, washed with water, saturated sodium bicarbonate, and brine, dried over magnesium sulfate, and subject to column chromatography |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
87% | With 1,3-bis(3,5-bis(trifluoro-ethyl)phenyl)thiourea In toluene at 20℃; for 24h; | 3.1. General Procedure for the Synthesis of Racemic Azocompounds (±)-1-6b General procedure: The corresponding -ketoester 1-6a (5.0 mmol) was dissolved at room temperature in toluene(8.0 mL) and N-tert-butyl formaldehyde hydrazone (10 mmol) was added. For the ethyl benzoylformate,catalyst I (0.5 mmol, 10 mol%) was added prior to the hydrazone. Reactions were stirred at roomtemperature for 24 h until consumption of the starting material (TLC). The solvent was eliminatedunder reduced pressure and the obtained crudes were purified by column chromatography usingtoluene/EtOAc mixtures as the eluent in order to obtain the corresponding racemic azocompounds(±)-1-6b with yields between 80 and 92%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
80.7% | With hydrazine hydrate In ethanol at 0 - 30℃; for 16h; | 1 Example 1 0.31 g (5 mmol) of 80% hydrazine hydrate was dissolved in 20 ml of absolute ethanol and placed in a constant pressure dropping funnel. 1.78 g (10 mmol) of benzoylformate was weighed into a 250 ml three-necked flask, and added to 50 ml of absolute ethanol, and the hydrazine hydrate solution was slowly added dropwise while stirring at 0 ° C. After the completion of the dropwise addition, the reaction was further stirred at room temperature (25 to 30 ° C) for 16 hours. The residue after evaporation of the solvent, Recrystallization from absolute ethanol gave 1.42 g of pale yellow crystals. The yield was 80.7% (based on the amount of ethyl benzoylformate). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
88% | With tert.-butylhydroperoxide; tetra-(n-butyl)ammonium iodide In water at 60℃; for 2h; Sealed tube; | Experimental procedure for the synthesis of 3aa General procedure: A sealed tube equipped with a magnetic stirring bar is charged with α-carbonyl aldehyde 1a (1.0 eq.) and alkyl halide 2a (1.0 eq.) in TBHP (2.0 eq.) along with TBAI (1.0 eq.). The resulting mixture was stirred at 60 °C for 2 h. After completion of the reaction (monitored using TLC), 10 mL of saturated Na2S2O3 solution and ethyl acetate (10 mL) were added to the reaction mixture. The organic layer after separation was washed with water (10 mL), dried over anhydrous Na2SO4 and concentrated under reduced pressure. The residue was purified by column chromatography on 100:200 mesh silica gel by using n-hexane:ethyl acetate (95:5) as an eluent to obtain the corresponding α-ketoester 3aa. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
98% | Stage #1: pinacol benzylboronate With 1,4-diaza-bicyclo[2.2.2]octane; sec.-butyllithium In tetrahydrofuran; hexane at -78℃; for 0.5h; Inert atmosphere; Stage #2: phenylglyoxylic acid ethyl ester In tetrahydrofuran at -78 - 20℃; for 3.25h; Inert atmosphere; chemoselective reaction; | General Procedure for Benzyl Addition to Ketones General procedure: A flame dried 25 mL round-bottom flask was charged with a magnetic stir bar, DABCO (0.50 mmol, 1equiv.), covered with a new septum and sealed thoroughly with Parafilm. The flask was allowed to coolunder vacuum and purged three times with argon before adding benzylboronic acid pinacol ester (178 μL,0.8 mmol, 1.6 equiv.) and 5 mL of THF. The contents were cooled to -78 C under increased argon flowbefore addition of sec-butyllithium (0.7 mmol, 1.4 equiv., 1.3 M in hexanes) and allowed to stir at thattemperature for 30 minutes. Subsequently, ketone (0.50 mmol, 1 equiv.) was added at -78 C neat or as asolution in THF (2 mL). The reaction was removed from the bath after an additional 15 minutes andallowed to warm to room temperature while stirring for 3 hours. The reaction was quenched with 0.2 mlsat. NH4Cl and concentrated under reduced pressure and isolated by column chromatography, elutingwith hexanes/ethyl acetate. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
92% | Stage #1: phenylglyoxylic acid ethyl ester; acetic acid hydrazide In ethanol at 25℃; for 1h; Stage #2: With ethylenediaminetetraacetic acid In ethanol at 25℃; for 3.33333h; Further stages; | 1-10 (Example 1)The method for preparing fentrazone by the one-pot method of this embodiment is specifically as follows: When equipped with a thermometer,Add 178.18g ethyl benzoylformate (1.0mol) into the 1000mL reaction flask of the reflux condenser,Temperature control 25,Drop 194.5g,40wt% acethydrazine in ethanol solution (1.05mol),After about 1h, add 11.7g of EDTA (0.04mol), keep it at 25 and react for 3h.Then add 14.6g of EDTA (0.05mol),After stirring for 20 minutes, a solid precipitated out.Continue to incubate at 25°C for 5h,Sampling control is qualified,Stop the reaction.Then add 147g of ethanol to dilute the reaction solution, then add sodium carbonate to adjust the pH of the reaction solution to 7, and stir for 30 min.Cool the reaction solution of step to 15°C, add 63.8g, 80wt% hydrazine hydrate (1.02mol) dropwise for about 1h, keep the temperature at 15°C and react for 7h, the sampling is qualified and stop the reaction.Add 49.2g of anhydrous sodium acetate (0.6mol) and 1.61g of tetrabutylammonium bromide (0.005mol) to the reaction solution of step , stir evenly, and heat to reflux (95±3) for 8h. The sampling is qualified and the reaction is stopped.Slowly lower the temperature of the reaction liquid of step to 0°C, precipitate solids, stir for 30min, and filter with suctionA light yellow solid wet product is obtained,Beat with ice water,Suction filtration,Dry at 60,Get pale yellowcrystalbodyFentrazone186.0g,HPLC purity is 99.2%,The yield was 92.0%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sodium hydrogencarbonate at 100℃; Overall yield = 78 percent; | Ethyl benzoylformate (1.1 equiv, 1.96 g, 0.011 mol) was added to a suspension of 4-hydrazinobenzenesulfonic acid hemihydrate (1 equiv, 1.88 g, 0.01 mol) in water (5 mL) at 100 °C. Heating was stopped once all the solids were dissolved. Then sodium bicarbonate was added until the pH of the solution turned 7 followed by the addition of sodium chloride to precipitate the product. Overall yield: 78% (Z/E=8/2)after reversed-phase column chromatography (water: ethanol=1: 1).1-Z 1H NMR (500 MHz, D2O) 7.68 (d, J = 8.7 Hz, 2H), 7.61 (d, J = 6.5 Hz, 2H), 7.43 - 7.35 (m, 3H), 7.32(d, J = 7.2 Hz, 2H), 4.31 (q, J = 7.2 Hz, 2H), 1.24 (t, J = 7.1 Hz, 3H) ppm; 13C NMR (126 MHz, D2O) δ163.19, 144.94, 135.79, 135.40, 130.09, 128.37, 128.16, 127.99, 126.87, 113.63, 62.06, 13.17. m.p. 96.0- 96.7 °C. High Res ESI-MS: C16H15N2O5S-: 347.0705 (calculated: 347.0702).1-E 1H NMR (500 MHz, D2O) δ 7.64 (d, J = 8.9 Hz, 2H), 7.58 - 7.38 (m, 3H), 7.37 - 7.31 (m, 2H), 7.19 (d,J = 8.9 Hz, 2H), 4.26 (q, J = 7.1 Hz, 2H), 1.24 (t, J = 7.1 Hz, 3H) ppm; 13C NMR (126 MHz, D2O) δ 166.17,144.96, 135.93, 135.66, 130.17, 129.67, 129.50, 129.11, 126.90, 114.03, 62.73, 13.35. High Res ESI-MS:C16H15N2O5S-: 347.0703 (calculated: 347.0702). The melting point is not reported because of thermalrelaxation when heating above 120 °C. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1: 48% 2: 7% | With 2,6-dimethylpyridine; tetrabutylammonium perchlorate; oxygen In water; acetonitrile at 20℃; Electrochemical reaction; | 2.2. Procedures for synthesis of products 3 a-n General procedure: A 20 mL two-necked round-bottomed flask was charged with the substrate (0.50 mmol), NHPI (0.20 mmol), 2,6-lutidine (0.30 mmol) and n-Bu 4 NClO 4 (1.0 mmol). The flask was then equipped with a condenser, a carbon paper (1.0 cm ×1.0 cm) an- ode and a platinum net (1.0 cm ×1.0 cm) cathode, and flushed with oxygen. Acetonitrile (9.5 mL) and water (0.5 mL) were then added. The electrolysis was carried out at 60 °C using a constant current of 5 mA until cell voltage at 3.0 V. The reaction mixture was cooled to room temperature and concentrated under reduced pressure. The residue was chromatographed through silica gel elut- ing with ethyl acetate/petroleum ether (4:1) to give the desired product. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
94% | With methanol; sodium methylate; C42H38Br2Sn; sodium iodide In hexane at 0℃; for 3h; Inert atmosphere; Optical yield = 72 percent ee; stereoselective reaction; | General Experimental Procedure for the Asymmetric Aldol Reaction of Alkenyl Esterswith a-Ketoesters (Tables 2-4): General procedure: A mixture of chiral tin dibromide 4a (16.5 mg, 0.02 mmol), NaI (6.0 mg, 0.04 mmol), andMeOH (25 μL, 0.625 mmol) in dry hexane (3 mL) was stirred for 10 min. Then, 1MNaOMe in MeOH (20 μL, 0.02 mmol) was added and the resulting mixture was stirred for 30min. Subsequently, a-ketoester 2a-2l (0.25 mmol) and alkenyl ester 1a-1l (0.375 mmol)were added to the mixture at 0 °C. After being stirred for 3 h at this temperature, thereaction mixture was treated with solid KF (0.5 g) and brine (3 mL) at ambient temperaturefor 5 min. The resulting precipitate was filtered off and the filtrate was extracted withAcOEt three times. The combined organic extracts were washed with brine and dried overNa2SO4 and then concentrated in vacuo. The residual crude product was purified by columnchromatography on silica gel to give corresponding b-hydroxy ketone 3aa-3la. Then, themixture was filtered with a glass filter funnel filled with Celite and washed with EtOAc, andthe combined filtrate and washes were concentrated in vacuo. The residual crude productwas purified by column chromatography on silica gel to give corresponding b-hydroxy ketone3aa-3la. The diastereomeric ratio was determined by 1H NMR analysis. Theenantioselectivity of the major diastereomer was determined by HPLC analysis using a chiralcolumn. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
92% | With Hexamethylphosphorous triamide In dichloromethane at -78 - 20℃; for 8h; | 2 Example 2 A 25ml reaction test tube was added with a magneton, and then 0.0178g (0.1mmol) of the compound represented by the formula I-1 and 0.0124g (0.1mmol) of the compound represented by the formula II-1 were dissolved in 1ml of dichloromethane. Add 0.0179 g (0.1 mmol) of catalyst tris(dimethylamino)phosphine at -78°C into the test tube, then slowly raise to room temperature for reaction, and the reaction is complete after 8 h. Remove the organic solvent under reduced pressure, carry out column chromatography elution, column chromatography petroleum ether (PE): ethyl acetate (EA)=6:1 to obtain the target product shown in formula III-1, the product III-1 is Liquid, the yield is 92%, and its reaction formula is as follows: |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
99% | With Hexamethylphosphorous triamide In dichloromethane at -78 - 20℃; for 8h; | 3 Example 3 A 25ml reaction test tube was added with magneton, and then 0.0178g (0.1mmol) of the compound represented by formula I-2 and 0.0111g (0.1mmol) of the compound represented by formula II-2 were weighed and dissolved in 1ml of dichloromethane. Add 0.0179 g (0.1 mmol) of catalyst tris(dimethylamino)phosphine at -78°C and add it to the test tube, then slowly raise to room temperature for reaction, the reaction is complete after 8 h, the organic solvent is removed under reduced pressure, eluted by column chromatography, column Chromatography petroleum ether (PE): ethyl acetate (EA)=6:1 to obtain the product that is the target product shown in formula III-2, and this product III-2 is a liquid with a yield of 99%, and its reaction formula is as follows: |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95% | With Hexamethylphosphorous triamide In dichloromethane at -78 - 20℃; for 8h; | 4 Example 4 A 25ml reaction test tube was added with a magneton, and then 0.0178g (0.1mmol) of the compound represented by formula I-3 and 0.0100g (0.1mmol) of the compound represented by formula II-3 were weighed and dissolved in 1ml of dichloromethane. Add 0.0179 g (0.1 mmol) of tris(dimethylamino) phosphine at -78°C and add it to the test tube, then slowly raise to room temperature for reaction, the reaction is complete after 8 h, remove the organic solvent under reduced pressure, elute by column chromatography, and then column chromatography Petroleum ether (PE): ethyl acetate (EA)=6:1 obtains the product that is the target product shown in formula III-3, this product III-3 is liquid, and productive rate is 95%, and its reaction formula is as follows: |
Tags: 1603-79-8 synthesis path| 1603-79-8 SDS| 1603-79-8 COA| 1603-79-8 purity| 1603-79-8 application| 1603-79-8 NMR| 1603-79-8 COA| 1603-79-8 structure
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H261 | In contact with water releases flammable gas |
H270 | May cause or intensify fire; oxidizer |
H271 | May cause fire or explosion; strong oxidizer |
H272 | May intensify fire; oxidizer |
H280 | Contains gas under pressure; may explode if heated |
H281 | Contains refrigerated gas; may cause cryogenic burns or injury |
H290 | May be corrosive to metals |
Health hazards | |
Code | Phrase |
H300 | Fatal if swallowed |
H301 | Toxic if swallowed |
H302 | Harmful if swallowed |
H303 | May be harmful if swallowed |
H304 | May be fatal if swallowed and enters airways |
H305 | May be harmful if swallowed and enters airways |
H310 | Fatal in contact with skin |
H311 | Toxic in contact with skin |
H312 | Harmful in contact with skin |
H313 | May be harmful in contact with skin |
H314 | Causes severe skin burns and eye damage |
H315 | Causes skin irritation |
H316 | Causes mild skin irritation |
H317 | May cause an allergic skin reaction |
H318 | Causes serious eye damage |
H319 | Causes serious eye irritation |
H320 | Causes eye irritation |
H330 | Fatal if inhaled |
H331 | Toxic if inhaled |
H332 | Harmful if inhaled |
H333 | May be harmful if inhaled |
H334 | May cause allergy or asthma symptoms or breathing difficulties if inhaled |
H335 | May cause respiratory irritation |
H336 | May cause drowsiness or dizziness |
H340 | May cause genetic defects |
H341 | Suspected of causing genetic defects |
H350 | May cause cancer |
H351 | Suspected of causing cancer |
H360 | May damage fertility or the unborn child |
H361 | Suspected of damaging fertility or the unborn child |
H361d | Suspected of damaging the unborn child |
H362 | May cause harm to breast-fed children |
H370 | Causes damage to organs |
H371 | May cause damage to organs |
H372 | Causes damage to organs through prolonged or repeated exposure |
H373 | May cause damage to organs through prolonged or repeated exposure |
Environmental hazards | |
Code | Phrase |
H400 | Very toxic to aquatic life |
H401 | Toxic to aquatic life |
H402 | Harmful to aquatic life |
H410 | Very toxic to aquatic life with long-lasting effects |
H411 | Toxic to aquatic life with long-lasting effects |
H412 | Harmful to aquatic life with long-lasting effects |
H413 | May cause long-lasting harmful effects to aquatic life |
H420 | Harms public health and the environment by destroying ozone in the upper atmosphere |
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