Preparation and application background and overview of 4-ethoxycarbonylphenylboronic acid
4-Ethoxycarbonylphenylboronic acid is an organic intermediate, which can be prepared by the reaction of ethyl 4-iodobenzoate and triisopropyl borate. 4-Ethoxycarbonylphenylboronic acid can be used to prepare 4-carboxyphenylboronic acid. 4-Carboxyphenylboronic acid is a very important chemical intermediate and is widely used in medicine and other fields. Boric acid compounds can undergo Suzuki reactions with chlorine, bromine or iodinated aromatics and alkenes, thereby connecting a variety of groups, and the downstream products are very rich.
Preparation and application of 4-ethoxycarbonylphenylboronic acid
Preparation and application report of 4-ethoxycarbonylphenylboronic acid 1.
A.Synthesis of ethyl 4-iodobenzoate
In a 250mL three-necked flask, dissolve p-iodobenzoic acid (20.0g, 80.6mmol) in ethanol (100.0mL), slowly add 98% concentrated sulfuric acid (8.7g, 88.7mmol), and reflux for 5 hours. After the reaction was completed, the reaction was evaporated to dryness under reduced pressure, and the residue was washed with water (20 mL×2) and dried under vacuum to obtain 20.9 g of ethyl 4-iodobenzoate, with a yield of 94.0%.
B.Synthesis of 4-ethoxycalcium carbonatecarbonylphenylboronic acid
In a 500mL three-necked flask, dissolve ethyl 4-iodobenzoate (20.9g, 75.8mmol) in anhydrous THF (300.0mL), and add sodium propyl triisopercarbonate borate (42.8g, 227.4mmol) , the temperature was lowered to -78°C, n-butyllithium (9.7g, 151.6mmol) was added dropwise, and the temperature was maintained for 0.5h. After the reaction is completed, quench the reaction with saturated aqueous ammonium chloride solution, adjust the pH value to 1 with 1mol/L hydrochloric acid, extract with ethyl acetate (150.0mL×3), combine the organic phases, wash with saturated brine (100mL×1), and anhydrous Dry with sodium sulfate, evaporate the solvent under reduced pressure, beat the residue with n-hexane, and filter with suction to obtain 13.5g of 4-ethoxycarbonylphenylboronic acid, with a yield of 92.0%.
Preparation and application report 2 of 4-ethoxycarbonylphenylboronic acid,
Into a 1L dry eggplant-shaped bottle with a condenser and a desiccator, add mL of absolute ethanol dried with 3A molecular sieves, 33.0g (0.2mol) of 4-carboxyphenylboronic acid, and 8mL of concentrated sulfuric acid, and reflux at 105 to 110°C. 24h, TLC (CHCl/MeOH=10/1) detects that there are very few raw materials. The ethanol is evaporated under reduced pressure to obtain a white solid. Add 500mL of water, filter, and wash with 250mL of saturated NaHCO3 solution. Wash with water until medium. properties and dried to obtain 33.5g of 4-ethoxycarbonylphenylboronic acid (yield 86.3%).
Preparation and application of 4-ethoxycarbonylbenzeneboronic acid
4-Ethoxycarbonylphenylboronic acid is used to prepare 4-carboxyphenylboronic acid. The method is as follows:
In a 500mL two-neck bottle, dissolve 4-ethoxycarbonylphenylboronic acid (13.5g, 69.7mmol) in THF (200mL), add 2.5mol/Laq sodium hydroxide (6.1g, 153.4mmol), and reflux for 3 hours. . After the reaction is completed, pour the reaction solution into ice water, extract impurities with ethyl acetate (20.0mL×2), adjust the pH value of the aqueous layer to 1 with 1mol/L hydrochloric acid solution, extract with ethyl acetate (100.0mL×3), and combine the organic phases. , washed with saturated brine (60 mL × 1), dried over anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure to obtain 11.0 g of the target product 4-carboxyphenylboronic acid. The yield is 95.2%. 1HNMR (MHz, CDCl3) δ8.16 (d, J = 8.1 Hz, 2H), 7.85 (d, J = 8.2 Hz, 2H).
References
[1][Chinese invention] CN201611003540.0 Preparation process of 4-carboxyphenylboronic acid
[2][China invention, China invention authorization] CN201510044744.8 A 3,4-dibenzamidobenzamide derivative and its preparation method and use
