3891-07-4

638-07-3

88150-75-8

a. Add 2400 mL of tetrahydrofuran to reaction flask A. Cool the mixture to -10°C or lower. Add 750 g of N-hydroxyethylphthalimide and 345 g of NaH sequentially (keep stirring at low speed during addition). Dropwise addition of ethyl 4-chloroacetoacetate was initiated within 30 minutes after addition of N-hydroxyethylphthalimide and NaH. The temperature of the reaction flask was maintained below -10 °C and 732 g of ethyl 4-chloroacetoacetate was slowly added dropwise, controlling the temperature below 0 °C. The dropwise process lasted for 1.5 to 2 hours. The temperature was then raised to 28 to 32 °C and the reaction was carried out for 5 to 6 hours. Upon completion of the reaction, 1500 mL of toluene was added and the temperature was lowered to below 5°C to obtain a toluene dilution of the reaction solution. b. In reaction flask B, 1700 mL of toluene, 2800 mL of water, and 1178 g of acetic acid were added and the temperature was maintained below 5°C. The toluene dilution of the reaction solution obtained in step a was slowly added to the reaction flask B at a temperature below 10°C. The addition process lasted from 1 to 1.5 hours. After stirring for 10 minutes, the mixture was allowed to stand for 15 minutes to separate and remove the aqueous layer. The toluene layer was washed five times with brine (2500 mL each time) with a mass fraction of 4%. Anhydrous magnesium sulfate was added to the washed toluene solution for drying, followed by concentration of the toluene solution under reduced pressure to remove toluene (not less than 2700 mL of toluene was removed, and the toluene content did not exceed a predetermined value) to ultimately obtain ethyl-4-(2-phthalimidoethoxy)acetoacetate in 93% yield.