The general procedure for the synthesis of ethyl dimethylphosphonoacetate from ethyl chloroacetate and trimethoxyphosphorus is as follows: a dry and clean 500 mL coil was heated to 150 °C. Take 1000g (0.7 eq., 8.16 mol) of ethyl chloroacetate (boiling point 142~145°C at standard atmospheric pressure) in reaction flask A and dilute it by adding 4000g of toluene. Another 1417g (1.0 eq., 11.42mol) of trimethoxyphosphine (boiling point at 112°C under standard atmospheric pressure) was placed in reaction vial B, and 3583g of toluene was added for dilution. After the coil temperature was stabilized, pump A (mixed solution of ethyl chloroacetate and toluene) and pump B (mixed solution of trimethoxyphosphine and toluene) were activated, both at a flow rate of 25.0 g/min. The residence time of the reactants in the reactor was 10 min, and the reaction pressure was maintained at 0.5~2.0 MPa. Upon completion of the reaction, the discharge port was directly connected to the thin-film evaporation device, and the evaporation pressure was controlled to 4~ 10×102 Pa, and the temperature was 95~105°C. Finally, 1344 g of ethyl dimethylphosphonoacetate (boiling point of 110~112°C, 466 Pa) was obtained with a yield of 84%.
