Structure of 946426-88-6
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CAS No. : | 946426-88-6 |
Formula : | C14H11Cl2NO3 |
M.W : | 312.15 |
SMILES Code : | O=C(C1=C(C2CC2)ON=C1C3=C(Cl)C=CC=C3Cl)OC |
MDL No. : | MFCD12964218 |
* 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 |
---|---|---|
87% | To a 50 mL round bottom flask containing <strong>[32249-35-7]methyl 3-cyclopropyl-3-oxopropanoate</strong> (1.3 g, 8.9 mmol) was added triethylamine (2.5 mL, 17.8 mmol). The resulting clear solution was stirred at room temperature for 15 minutes and was cooled in an ice water bath. To the stirring solution was added a solution of 2,6-dichloro-N-hydroxybenzimidoyl chloride (2.0 g, 8.9 mmol) in EtOH (4 mL) over the space of 10 minutes giving a white suspension. After addition, the resulting suspension was stirred at room temperature overnight. The reaction mixture was concentrated in vacuo and the residue was purified by flash chromatography on S1O2 (0-10% EtOAc/hexanes, Isco 80 g column) to give methyl 5- cyclopropyl-3-(2,6-dichlorophenyl)isoxazole-4-carboxylate (2.4 g, 7.7 mmol, 87% yield) as a white solid. NMR (500 MHz, CDCh) δ 7.45-7.39 (m, 2H), 7.39-7.33 (m, 1H), 3.71 (s, 3H), 2.93 (tt, J=8.5, 5.2 Hz, 1H), 1.47-1.40 (m, 2H), 1.34-1.27 (m, 2H). | |
87% | To a 50 mL round bottom flask containing <strong>[32249-35-7]methyl 3-cyclopropyl-3-oxopropanoate</strong> (1.3 g, 8.9 mmol) was added triethylamine (2.5 mL, 17.8 mmol). The resulting clear solution was stirred at room temperature for 15 minutes and was cooled in an ice water bath. To the stirring solution was added a solution of 2,6-dichloro-N-hydroxybenzimidoyl chloride (2.0 g, 8.9 mmol) in EtOH (4 mL) over the space of 10 minutes giving a whitesuspension. After stirring at room temperature overnight, the reaction mixture was concentrated in vacuo and the residue was purified by flash chromatography on 5i02 (0- 10% EtOAc/hexanes, Isco 80 g column) to give methyl 5-cyclopropyl-3-(2,6- dichlorophenyl)isoxazole-4-carboxylate (2.4 g, 7.7 mmol, 87% yield) as a white solid. ‘H NMR (500 MI-Tz, CDC13) ö 7.45-7.39 (m, 2H), 7.39-7.33 (m, 1H), 3.71 (s, 3H), 2.93 (if,J=8.5, 5.2 Hz, 1H), 1.47-1.40 (m, 2H), 1.34-1.27 (m, 2H). | |
87% | With triethylamine; In ethanol; at 20℃;Cooling with ice; | To a 50 mL round bottom flask containing <strong>[32249-35-7]methyl 3-cyclopropyl-3-oxopropanoate</strong> (1.3 g, 8.9 mmol) was added triethylamine (2.5 mL, 17.8 mmol). The resulting clear solution was stirred at room temperature for 15 minutes and was cooled in an ice water bath. To the stirring solution was added a solution of 2,6-dichloro-N-hydroxybenzimidoyl chloride (2.0 g, 8.9 mmol, synthesis described in General Method A) in EtOH (4 mL) over the space of 10 minutes giving a white suspension. After addition, the resulting suspension was stirred at room temperature overnight. The reaction mixture was concentrated in vacuo and the residue was purified by flash chromatography on SiO2 (0-10% EtOAc/hexanes, Isco 80 g column) to give methyl 5-cyclopropyl-3-(2,6-dichlorophenyl)isoxazole-4-carboxylate (2.4 g, 7.7 mmol, 87% yield) as a white solid. 1H NMR (500 MHz, CDCl3) δ 7.45-7.39 (m, 2H), 7.39-7.33 (m, 1H), 3.71 (s, 3H), 2.93 (tt, J=8.5, 5.2 Hz, 1H), 1.47-1.40 (m, 2H), 1.34-1.27 (m, 2H). |
84% | Triethylamine (8.2g) was added to <strong>[32249-35-7]methyl 3-cyclopropyl-3-oxopropionate</strong> (82mmol), Stir for 30 minutes. Then cool to 10C, Then add a solution of III-1 (18.3g, 82mmol) in absolute ethanol (80mL) dropwise (internal temperature does not exceed 30C), The reaction was overnight at room temperature. Add ethyl acetate (100mL) to dilute the reaction solution, wash with water, The aqueous phase was extracted with ethyl acetate (100 mL each time, 3 times in total). Mix the organic phase, Wash with saturated brine and concentrate. Add 100mL ether to the concentrate and stir, The solvent was removed under vacuum to obtain the solid product IV-1 (21.6 g, yield 84%). | |
65% | 3-Cyclopropyl-3-oxo-propionic acid methyl ester (31.7g, 0.223mol) was dissolved by adding triethylamine (45.1g, 62mL, 0.446mol),Stir at room temperature. After 30 minutes, cool down to 10 C.Slowly add 2,6-dichloro-benzaldehyde-chloro-oxime (50.0g, 0.223mol, dissolved in 300mL ethanol), the temperature during the dropwise addition does not exceed 24 C,After dripping, stir overnight at room temperature, monitor the reaction by thin layer chromatography (TLC), and add 200 mL of water after the reaction.Extracted with 500 mL of ethyl acetate (EA), extracted the aqueous layer three times with 200 mL of ethyl acetate, combined the organic layers, washed the organic layer with 200 mL of saturated brine, and dried over anhydrous Na2SO4.Concentrated in vacuo to 10% solution, a large amount of solids precipitated,The crude product was obtained by suction filtration, followed by grinding with 100 ml of hexane, suction filtration, and drying to obtain 45.0 g of a white solid with a yield of 65%. | |
54% | Triethylamine (10.91 g, 0.11 mol, 2.0 eq) was added to a mixture of <strong>[32249-35-7]methyl 3-cyclopropyl-3-oxopropionate</strong> (7.66 g, 0.054 mol, 1.0 eq) and stirred at room temperature for 30 min, And then cooled to 10 C.The intermediate 1-9 (12.10 g,0.054 mol, 1.0 eq) was dissolved in 24.2 mL of ethanol and slowly added to the above reaction solution, and the internal temperature did not exceed 24 C. In addition,Stir overnight at room temperature.After completion of the reaction, the reaction solution was diluted with 45 ml of ether, washed with 15 ml of water, separated, and the aqueous layer was extracted once with ethyl acetate.And the organic layer was washed with brine, dried over anhydrous sodium sulfate, filtered and the filtrate was concentrated to 10% of the total to form a precipitate which was washed with etherMashing beating, filtering, filter cake vacuum dry,To give intermediate 1-10, 8.48 g of a white solid,the yield was 54%. | |
54% | Triethylamine (10.91 g, 0.11 mol, 2.0 eq) was added to <strong>[32249-35-7]methyl 3-cyclopropyl-3-oxopropanoate</strong>(7.66 g, 0.054 mol, 1.0 eq) mixture was stirred at room temperature for 30 min and then cooled to 10 C.Intermediate 1-9 (12.10 g, 0.054 mol, 1.0 eq) was dissolved in 24.2 mL of ethanol.The reaction solution was slowly added thereto, and the internal temperature did not exceed 24 C. Further, the reaction was stirred at room temperature overnight. After the reaction, the reaction solution was diluted with 45 ml of EA, washed with 15 ml of water, and the mixture was evaporated.The organic layers were combined, washed with brine and dried over anhydrous sodium sulfateFilter and concentrate the filtrate to 10% of the total amount.A precipitate formed, which was beaten with ether and filtered, and the cake was vacuum dried.Intermediate 1-10 was obtained as a white solid, 8.48 g, yield 54%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
58% | With triethylamine; In ethanol; at 10 - 20℃; | At room temperature,to3-cyclopropyl-3-Oxypropionic acidMethyl ester (15.8 g, 111 mmol)Triethylamine (32 mL) was added dropwise. 10 C was added (Z) -2,6-dichlorobenzyl to the above system(0.5 g, 111 mmol, dissolved in 60 mL of ethanol) was added and the mixture was stirred overnight at room temperature. plusThe reaction was quenched with water (20 mL) and the reaction system was extracted with ethyl acetate (50 mL x 3)The crude phase was dried and concentrated to a crude product which was recrystallized from ethyl acetate / petroleum ether (1:10)5-cyclopropyl-3- (2,6-dichlorophenyl) isoxazole-4-carboxylate (1-4) (20 g, 58%) was whitesolid |
Tags: 946426-88-6 synthesis path| 946426-88-6 SDS| 946426-88-6 COA| 946426-88-6 purity| 946426-88-6 application| 946426-88-6 NMR| 946426-88-6 COA| 946426-88-6 structure
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