| 79% |
Stage #1: ortho-nitrobenzoic acid With 1,1'-carbonyldiimidazole In acetonitrile at 20℃; for 4h;
Stage #2: ethyl potassium malonate With triethylamine; magnesium chloride In acetonitrile at 20℃; for 1.5h; |
1 Example 1 Preparation of ethyl 3- (2-nitrophenyl) -3-oxopropionate (1)
A:O-nitrobenzoic acid (3.0 g, 18 mmol) and 30 mL of acetonitrile were mixed,20 ° C,N, N-carbonyldiimidazole (3.2 g, 19.8 mmol) was added portionwise,The reaction was carried out for 4 hours.Solution yellowish,clarify. B:takeA three neck flask was charged with monoethylammonium malonate (15.3 g, 90 mmol) in 60 mL of acetonitrile,Stirring.installationthermometer,MgCl2 (1.85 g, 19.44 mmol) was added in portions over about 15 min.The temperature of the reaction solution was slightly elevated.After the addition was complete, the mixture was stirred at 35 ° C for 30 min, then cooled to 25 ° C,Triethylamine (5.46 g, 54 mmol, 7.52 mL) was slowly added dropwise with stirring,With the addition of triethylamine,The reaction solution was thickened,A white lump appears.After stirring for 30 min. C:The reaction solution in A was added to B,The temperature is slightly elevated.Followed by stirring at 20 ° C for 1.5 hours. D:The pH of the reaction solution was adjusted to 2 to 5 by the dropwise addition of 3 mol / L HCl to the reaction solution,The reaction solution was maintained at a temperature of less than 20 ° C.After stirring for 20 min,A portion of acetonitrile (60 mL) was concentrated under reduced pressure,Then, 100 mL of ethyl acetate was added,Then 20 mL of water was added,Stirring,Liquid separation,The organic phase was washed with 50 mL of saturated NaHCO3 solution and 50 mL of saturated NaCl solution,Dispensing.Organic phase separation,Concentrated under reduced pressure,To give 3.4 g of ethyl 3- (2-nitrophenyl) -3-oxopropionate,Yield 79%As a light yellow liquid,20 ° C for 12h into a light yellow solid. |
| 78% |
Stage #1: ortho-nitrobenzoic acid With 1,1'-carbonyldiimidazole In acetonitrile at 20℃; for 4.5h;
Stage #2: ethyl potassium malonate With magnesium chloride In acetonitrile at 35℃; for 1.58333h;
Stage #3: With triethylamine In acetonitrile at 25℃; for 2.5h; |
Take the first three-necked flask with a capacity of 100 mL, put a magnetic stirrer into the bottle, and install a 100° C. thermometer, a three-way adapter, and a feeding funnel on the three ports, respectively. Add o-nitrobenzoic acid (3.00g, 17.95mmol, 1eq) and 30mL acetonitrile into the first three-necked flask, set the stirring temperature to 20°C, and heat up while stirring. Then N,N'-carbonyldiimidazole (3.20g, 19.75mmol, 1.1eq) was added to the three-necked flask in about 30 minutes. After the addition, the reaction solution A was stirred at 20°C for 4 hours. Take the second three-necked flask with a capacity of 250 mL, put a magnetic stirrer into the bottle, and install a 100°C thermometer, a three-way adapter, and a feeding funnel on the three ports. Respectively add monoethyl malonate potassium salt (15.28g, 89.75mmol, 5eq), 60mL acetonitrile into the second three-necked flask, set the stirring temperature to 35°C, heat up while stirring, and then add MgCl2 (1.85 g, 19.39 mmol, 1.08 eq) into the second three-necked flask in about 15 minutes. After the addition, the reaction solution B was stirred at an oil bath temperature of 35°C for 1 hour. After 1 hour, the stirring was turned off, and the reaction solution was naturally cooled to 25°C. When the temperature dropped to 25°C, triethylamine (5.45g, 53.85mmol, 3eq) was slowly added dropwise to the reaction solution B under stirring. During the dropping process, white lumps were formed, and the reaction solution became turbid. After the addition, the reaction solution B was stirred at 25°C for 30 min. After reaction solution A reacted for 4 hours, the solution changed from a turbid milky white liquid to a light yellow clear liquid. Dilute 1 drop of the reaction solution to 0.5 mL with ethyl acetate, monitor it with a TLC (Petroleum ether: Ethyl acetate = 2/1) point plate, and click three points, which are the raw material point, the cross point of the raw material and the reaction solution, and the reaction liquid point, observed under a dark box ultraviolet analyzer, it was found that the raw material (Rf=0.3) had reacted completely, and new spots were formed at (Rf=0.4, Rf=0.5). After the reaction of the reaction liquid B was completed, the reaction liquid B was a turbid white liquid. Take 1 drop of the reaction solution diluted with ethyl acetate to 0.5mL, monitor with TLC (Petroleum ether: Ethyl acetate = 2/1) point plate, point three points, namely the raw material point, the intersection of the raw material and the reaction liquid and the reaction liquid point were observed under a dark box ultraviolet analyzer, and it was found that the raw material (Rf=0.4) had reacted completely, and a new point was formed at (Rf=0.6). After the reaction is completed, the reaction solution A is slowly poured into the second three-necked flask containing the reaction solution B to obtain the reaction solution C, and the reaction solution C is stirred at 25° C for 2 hours. After two hours, take a 500 mL conical flask and fill it with 100 mL of water, and pour the reaction solution C into the conical flask to quench the reaction. Then, the pH of the reaction solution C was adjusted to pH=4 with 3 mol/L (90 mL) hydrochloric acid. After the reaction solution C was rotated away most of the acetonitrile with a rotary evaporator, it was extracted with ethyl acetate 3 times, with 100 mL each time. After three extractions, the water phase and the organic phase were plated, and the plate was climbed with (Petroleum ether: Ethyl acetate = 2/1). The TLC plate showed that the water phase had been completely extracted. The organic phase was washed twice with a saturated aqueous NaHCO3 solution, with 100 mL each time. After the washing is completed, the organic phase is washed twice with a saturated NaCl aqueous solution, 100 mL each time. Finally, the organic phase was dried with anhydrous sodium sulfate and spin-dried with a rotary evaporator. The temperature of the rotary evaporator was set to 50°C. After spin-drying, the weight was weighed to obtain 3.20g of a light yellow oily liquid. The spin-dried organic phase was subjected to nuclear magnetic identification using deuterated chloroform as a solvent, and it was determined that ethyl 3-(2-nitrophenyl)-3-oxopropionate (Compound II) was obtained with a yield of 78%. |
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