41051-15-4

32807-28-6

41051-15-4

The general procedure for the synthesis of methyl 4-methoxyacetoacetate from methyl 4-chloroacetoacetate is as follows: Example 1: 1. 77.4 g of 97% sodium methanol was suspended in 100 g of acetonitrile under nitrogen protection at ambient temperature. 2. 101.9 g of 97.5% methyl 4-chloroacetoacetate was slowly added dropwise through a dropping funnel over 5 to 6 minutes. The temperature rises during the reaction and the reaction temperature is maintained at 68 °C to 70 °C by cooling. 3. After the exothermic reaction had diminished, cooling was stopped and the reaction mixture was instead heated in a hot water bath at 70 °C. 4. the reaction mixture was continued to be stirred at 70 °C for 24 to 25 minutes, followed by slow addition to a cooling solution comprising 6 g of glacial acetic acid and 215 g of ice water under stirring. 5. Meanwhile, 37.4% hydrochloric acid was slowly added dropwise through a burette while the pH was monitored using a glass electrode to maintain the pH between 4.5 and 8 by adjusting the rate of titration of the reaction mixture and/or hydrochloric acid. At the end of neutralization, the pH should be controlled at 6.1 ± 0.1. 6. A total of 56.4 mL of 37.4% hydrochloric acid was used in the neutralization process and the reaction temperature was maintained at 30°C to 35°C. 7. The neutralized mixture was transferred to a separatory funnel and the organic layer was separated after standing and stratifying. 8. The aqueous layer was extracted once with 200 mL of acetonitrile and subsequently twice with 100 mL of acetonitrile each time. 9. The organic phases were combined and concentrated to constant weight on a rotary evaporator at 30°C to 35°C under 20 torr pressure. The recovered solvent can be used in the next batch. 10. The crude product is purified by distillation at 0.5 to 1.5 torr pressure at 90°C. Methyl 4-methoxyacetoacetate was obtained in 91.7% yield (based on the amount of methyl 4-chloroacetoacetate) and the purity of the product was 98.8%.