Synthesis
General procedure for synthesizing β-methylglutaric acid monomethyl ester from dimethyl 3-methylglutarate: 240 g of barium hydroxide octahydrate was added to methanol under stirring conditions to prepare 182 g of barium hydroxide methanol solution with a concentration of 10%, and cooled and set aside. Assemble a stirrer and a thermometer in a 5000 ml four-necked reaction flask, add the reaction solution of dimethyl β-methylglutarate prepared above, and cool it to below -10°C, controlling the temperature to not more than 0°C. Rapidly add the newly configured 10% barium hydroxide methanol solution with stirring, and a white solid precipitate was formed immediately after the addition. Gradually warmed to room temperature and stirred continuously for 16 hours. Upon completion of the reaction, it was filtered and washed with a small amount of methanol to give about 400 g of methyl beta-barium salt glutarate monomethyl ester wet product. Next, a stirrer, thermometer and dropping funnel were assembled on a 2000 ml four-neck reaction flask. The wet product of methyl β-barium salt glutaric acid monomethyl ester prepared in the previous step was added, 1000 ml of distilled water was added, stirring and pulping was carried out, the temperature was controlled not to exceed 0°C, 10% hydrochloric acid was added dropwise to adjust the pH to 3-4, and stirring was continued for 30 minutes. To the reaction mixture was added 300 ml of ether, stirred for 10 minutes, and then the ether layer was separated using a separatory funnel. The aqueous layer was extracted once more with 200 ml of ether. The organic layers were combined and evaporated. The organic layer was filtered to remove the desiccant. The ether was recovered by atmospheric pressure distillation followed by reduced pressure distillation. Fraction 230 g at 146-150°C/10 mmHg was collected as monomethyl β-methylglutarate, which was analyzed by gas chromatography and showed a purity of 98.50% and a yield of 94.4%.
References
[1] Organic and Biomolecular Chemistry, 2018, vol. 16, # 8, p. 1343 - 1350
[2] Patent: CN108383723, 2018, A. Location in patent: Paragraph 0033; 0034; 0046-0048; 0053; 0057-0063; 0068-0074
